Chronic Cough

Chronic Cough. Nevertheless, there may be a cohort of patients with chronic cough who would benefit from earlier chest CT, potentially leap-frogging weeks of sequential Chronic Cough therapeutic trials that may in fact delay diagnosis. Future research may be needed to evaluate which patients with chronic cough would gain from earlier evaluation with CT. FDG-PET/CT Skull Base to Mid-Thigh There is no relevant literature to support the use of FDG-PET/CT in the evaluation of chronic cough with increased risk factors for lung cancer. FDG-PET utilizes a radiolabeled glucose analog to evaluate for upregulated metabolism in areas of infection, inflammation, and neoplasm [43]. It is often utilized in the setting of solitary pulmonary nodules to allow for risk stratification. In the setting of known malignancy, FDG-PET is suitable for staging nodal and metastatic involvement. FDG-PET provides valuable input for further noninvasive testing and operative planning. In patients with chronic cough who have elevated risk factors for lung cancer, it is unlikely that FDG- PET would significantly add value over other imaging modalities, such as chest radiography or chest CT. MRI Chest There is no relevant literature to support the use of thoracic MRI in the evaluation of patients with chronic cough who have increased risk of lung cancer. No studies specific to chronic cough distinguished between contrast- enhanced and noncontrast MRI. In the setting of neoplasm of the chest wall or mediastinum, the addition of extracellular contrast agent would allow for differentiation of cystic and solid features and may add value in planning appropriate invasive testing. Additionally, vasculature is imaged well with the addition of contrast, and contrast-enhanced MRI has been shown to be nearly equivalent to contrast-enhanced CT for the evaluation for pulmonary embolism [29]. MRI was not evaluated in the two prospective clinical series evaluating the utility of a standardized clinical protocol for the evaluation of chronic cough [7,17].


Chronic Cough

Chronic Cough. MRI is also not explicitly recommended in the available practice guidelines for the evaluation of chronic cough by the ACCP [1]. Limitations of pulmonary MRI include low signal-to-noise ratio (especially with normally aerated lung), low spatial resolution, and need for adequate breath-hold technique or respiratory gating [46]. Based on our literature review, there is limited evidence evaluating the diagnostic quality of MRI for the evaluation of pulmonary abnormalities. Ohno et al [47] analyzed 85 consecutive patients with a high prevalence of pulmonary abnormality with high-resolution pulmonary MR using ultrashort time to echo and compared findings with both standard and LDCT acquisition. High-resolution MRI demonstrated excellent correlation with standard dose CT for mass or nodule, GGO, and lymphadenopathy. MRI demonstrated 89% sensitivity and 99% specificity for mass or nodule identification. The authors noted diminished imaging quality; however, this did not affect overall evaluation. The role of MRI in the setting of chronic cough and increased cancer risk remains unknown at this time. Future research in this setting may be warranted for certain populations. CT Chest The most commonly identified etiologies reported for chronic cough are asthma, GERD, and UACS [1]. Prospective case series have shown clinical efficacy in diagnosing and managing chronic cough using standard clinical algorithms with minimal investigation [7,17]. When this has failed to result in diagnosis, or when empiric sequential treatment for the most common etiologies has failed to resolve symptoms, further investigative modalities and additional specialty referrals have been recommended. The ACCP and German Respiratory Society both recommend HRCT after an appropriate clinical evaluation and empiric trial has been performed [1,29]. HRCT is typically performed with multidetector helical CT, and the standard for performance can be reviewed in the ACR practice parameter for HRCT [54].


Chronic Cough

Chronic Cough. Briefly, thin-slice acquisition and high spatial resolution reconstruction algorithms allow for near-isotropic voxels. This gives the reader additional tools for a thorough evaluation of the imaged field, including multiplanar reformats and both maximum and minimum intensity projection postprocessed images. In the setting of chronic cough, however, the various modalities and specific protocol designs have not been adequately investigated and compared. It is unclear how much the added resolving power of HRCT adds to the clinical evaluation of patients with chronic cough. Contrast- and noncontrast-enhanced studies have also not been compared. The addition of contrast would allow for improved visualization of the mediastinum, chest wall, and soft Chronic Cough HRCT is considered the reference standard for the evaluation of bronchiectasis. Bronchiectasis has been identified as an etiology for chronic cough in up to 8% of patients in case series [2,7]. Although suspicion for bronchiectasis can be aided by clinical features [5], chest radiography has shown poor sensitivity for evaluation. Altenburg et al [32] reported that radiographic findings did not detect ectatic airways in up to 34% of patients reviewed. Bronchiectasis and bronchial wall thickening were identified in 27% and 21% of patients, respectively, referred to chest CT for the evaluation of chronic cough in whom radiographs were reportedly normal [3]. There remains variable association between identification of bronchiectasis and clinical features. Bronchiectasis has been found by chest CT in asymptomatic persons enrolled in a health survey screening setting [4], as well as in asymptomatic elderly persons [37]. Wilsher et al [40] evaluated 60 consecutive patients with newly diagnosed RA and were unable to demonstrate a correlation between cough symptoms and bronchiectasis, although association reached significance for dyspnea.


Chronic Cough

Chronic Cough. Furthermore, bronchiectasis and bronchial wall thickening were identified in 48% and 58% of patients, respectively, with only 30% reporting any symptoms. Ooi et al [6] were unable to correlate the frequency of acute symptom exacerbation (including cough symptoms) and the degree of bronchial wall thickening in 60 consecutive patients with CT-proven bronchiectasis. In a large single-center prospective study, Grydeland et al [39] used quantitative analysis of bronchial wall thickening and compared findings between patients with COPD (n = 463) and those without COPD (n = 488). Airway wall thickening was found to be statistically associated with chronic cough in patients with COPD but did not reach significance in the non-COPD group. Interstitial lung disease and pulmonary fibrosis have been reported as etiologies of chronic cough, although prevalence of diagnosed cases is variable, ranging between 0.4% and 8% of the reviewed case series [2,7,16,17]. Chest CT is considered the reference standard in the evaluation of interstitial lung disease. Although at least one study reported good correlation between chest radiography and chest CT in this setting [46], chest CT has been shown to be more sensitive than both chest radiography [31] and LDCT [27]. In 97 patients with chronic cough who also had normal chest radiographs, Truba et al [3] reported interstitial abnormalities in 4 patients. Association between cough symptoms and CT findings of interstitial lung disease has been variable. In a small prospective cohort of 36 patients with RA, cough was not found to be statistically associated with restrictive findings on either PFT or HRCT analysis [31]. In 107 consecutive patients with systemic sclerosis, cough was associated with HRCT findings [31]. In the setting of chronic cough after failed initial evaluation and/or empiric treatment, the limited evidence suggests a role for chest CT to identify underlying pulmonary disease.


Chronic Cough

Chronic Cough. Although it remains unclear if HRCT or LDCT play a role, clinical features may stratify patients for appropriate imaging evaluation in order to balance diagnostic yield and dose considerations. CT Maxillofacial CT of the sinuses and maxillofacial structures offers improved visualization of the sinonasal anatomy, allowing for localization, characterization, and grading of sinonasal pathology. UACS is largely a conglomerate terminology for cough related to inflammation or irritation of the upper airways, which includes postnasal drip, allergic and nonallergic CRS, as well as laryngeal reflux. UACS is considered one of the more common causes of chronic cough [1,53]. Based on a few case series of patients with chronic cough, UACS/rhinitis prevalence ranged from 6% to 65% [2,7,17]. Guidelines for the evaluation of chronic cough by the ACCP places sinus imaging under consideration after initial clinical examination and chest radiography [1]. The clinical evaluation of UACS is not sensitive and often not specific [53], and features may go unrecognized even by endoscopy [12,55,56], creating an integral role for noninvasive imaging. Symptoms alone were found to have a sensitivity between 37% and 73% in a retrospective analysis of 126 patients who underwent CT imaging for the evaluation of CRS [57]. Furthermore, up to 35% of patients who were diagnosed with CRS had normal endoscopic findings [57]. Abrass et al [55] reviewed 100 patients with clinical findings suspicious of CRS, all with negative endoscopic evaluations. The investigators reported between 20% and 49% of studied individuals had positive findings on point-of-care CT of the sinuses, and the utilization of imaging allowed for a decrease in unnecessary antibiotic prescription. In a small retrospective case control study evaluating patients with CRS, Conley et al [56] showed increased clinical accuracy and a lower rate of unnecessary antibiotic use when cone-beam CT was used to evaluate the sinuses at initial office visit. In a


Female Breast Cancer Screening

Female Breast Cancer Screening.  Introduction/Background Breast cancer is the most common nonskin cancer diagnosis in women and is second only to lung cancer with respect to cancer deaths. Early detection of breast cancer from regular screening substantially reduces breast cancer mortality [1]. Because regular screening identifies tumors when they are smaller and with fewer nodal metastases, patients with screen-detected breast cancers are less likely to require mastectomy or chemotherapy, thereby also decreasing morbidity [2]. Breast cancer risk is frequently divided into 3 major categories: average, intermediate, and high risk. Numerous factors contribute to breast cancer risk, so no single method or definition is used to classify each woman into a specific risk category [3,4]. The use of validated statistical models based largely upon family history, which also incorporate additional risk factors, represents one mechanism to estimate risk. Currently, risk categories are most frequently defined by estimated lifetime risk; however, different time horizons, such as 5 or 10 year risk, may also be valuable for guideline development and informed decision-making [3]. Women at average risk are typically defined as those with <15% estimated lifetime risk for developing breast cancer, whereas intermediate-risk women are generally defined as those with a 15% to 20% estimated lifetime risk. The high-risk category typically includes women who have a >20 to 25% estimated lifetime risk: women who carry a deleterious genetic mutation that increases breast cancer risk, as well as untested first-degree relatives of patients with these mutations and women who have received radiation therapy to the thorax or upper abdomen at an early age (<30 years).


Female Breast Cancer Screening

Female Breast Cancer Screening. Some women with a personal history of high-risk breast lesions, a personal history of breast cancer, dense breast tissue, or a family history of breast cancer may fit into the intermediate- or high-risk categories, depending upon their specific risk factors or combination of factors [3]. Elevated risk is sometimes used to refer to women in both the intermediate- and high-risk categories [3]. Breast cancer screening guidelines vary across medical professional organizations, although published guidelines agree that regular breast cancer screening decreases morbidity and breast cancer mortality [5-7]. Medical professional organizations may also define breast cancer risk categories using different methodologies. Although screening guidelines for high-risk patients have typically been similar, discrepant recommendations for average- and intermediate-risk women have sparked controversy and confusion. In part due to differences in screening guidelines, use of breast cancer screening modalities remains suboptimal in women of all risk categories. The ACR encourages patients to undergo breast cancer risk assessment by 25 years of age, so elevated-risk patients have the opportunity to benefit from earlier and more aggressive breast cancer screening regimens, when appropriate [3]. The ACR recommends that both the benefits and risks of breast cancer screening and supplemental screening be considered to assist patients in making informed decisions regarding their health care [8]. aPanel Chair, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. bMemorial Sloan Kettering Cancer Center, New York, New York. cMemorial Sloan Kettering Cancer Center, New York, New York. dPanel Vice-Chair, University of Cincinnati, Cincinnati, Ohio. eClinica Family Health, Lafayette, Colorado; American Academy of Family Physicians. fLenox Hill Hospital, Northwell Health, New York, New York; American College of Surgeons. gWashington University School of Medicine, Saint Louis, Missouri.


Female Breast Cancer Screening

Female Breast Cancer Screening. hPenn State Health Hershey Medical Center, Hershey, Pennsylvania. iThomas Jefferson University Hospital, Philadelphia, Pennsylvania; American College of Obstetricians and Gynecologists. jUniversity of Utah, Salt Lake City, Utah. kKaiser Permanente, Atlanta, Georgia. lUniversity of Michigan, Ann Arbor, Michigan. mSt. Bernards Healthcare, Jonesboro, Arkansas. nUMass Memorial Medical Center/UMass Chan Medical School, Worcester, Massachusetts. oNYU Clinical Cancer Center, New York, New York. pProMedica Breast Care, Toledo, Ohio. qEmory University Hospital, Atlanta, Georgia; RADS Committee. rYale School of Medicine, New Haven, Connecticut; Society of General Internal Medicine. sHarvard Medical School, Boston, Massachusetts; American Geriatrics Society. tLoyola University Chicago, Stritch School of Medicine, Department of Radiation Oncology, Cardinal Bernardin Cancer Center, Maywood, Illinois; Commission on Radiation Oncology. uHoag Family Cancer Institute, Newport Beach, California and University of Southern California, Los Angeles, California; Commission on Nuclear Medicine and Molecular Imaging. vSpecialty Chair, Boston University School of Medicine, Boston, Massachusetts. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: publications@acr.org Female Breast Cancer Screening Discussion of Procedures by Variant Variant 1: Adult female. Breast cancer screening. Average risk.


Female Breast Cancer Screening

Female Breast Cancer Screening. Digital Breast Tomosynthesis Screening Digital breast tomosynthesis (DBT) displays reconstructed stacked images of the breast in combination with digital mammographic views, which may be synthetic mammograms reconstructed from the acquired tomosynthesis data set or full-field digital mammograms (FFDM). Compared to FFDM or synthetic mammograms alone, most studies demonstrate that DBT increases cancer detection rate (CDR) and decreases recall rate [14-22]; although some studies have not reached statistical significance [23] or have found less compelling results in subsets of women, such as those with extremely dense breasts [24,25]. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27]. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk. Irrespective of risk category, meta-analyses have demonstrated an incremental increase in CDR of 1.6 to 3.2 per 1,000 screening DBT examinations and a 2.2% pooled decrease in recall rate compared to digital mammography [18,29,30]. Because screening mammography decreases breast cancer mortality, screening mammography or screening DBT is still performed in women undergoing supplemental screening studies [3,8,35]. In addition to mortality reduction, screening mammography decreases treatment morbidity, because screen-detected tumors are typically lower stage (eg, smaller and more likely to be node-negative), compared to breast cancers detected by palpation [2,8]. Despite these benefits, screening mammograms also have risks. The most common perceived risks include false-positive recalls and biopsies, overdiagnosis, and patient anxiety [5,7,32].


Female Breast Cancer Screening

Female Breast Cancer Screening. Approximately 10% of screening mammograms result in a recall for additional imaging, although <2% result in a Female Breast Cancer Screening For women 40 to 49 years of age, randomized controlled trials and observational studies demonstrate that screening mammography decreases breast cancer mortality by 15% to 50% [1,8,32,33,39]. Results from the Cancer Intervention and Surveillance Modeling Network (CISNET) suggest that annual screening mammography in women 40 to 49 years of age saves 42% more lives and life-years than biennial screening due to faster growing tumors in younger women [31]. Women screened between 40 and 49 years of age are also less likely to require mastectomy or chemotherapy than women diagnosed with palpable tumors [2]. Non-Hispanic Black, Hispanic Black, and Hispanic White women have higher breast cancer mortality than non- Hispanic White women, and minority women often present at younger ages with more aggressive tumor subtypes [3,8]. Therefore, decreasing access to screening mammography, especially in women 40 to 49 years of age, may disproportionately impact minority women. Annual screening mammography results in a greater reduction in mortality compared to biennial screening [8]. In women 40 to 84 years of age, annual screening reduces mortality by 40%, compared to a 32% reduction for biennial screening [32]. With regular screening, interval breast cancers do occur with a higher frequency in women undergoing biennial or triennial screening compared to annual screening. The sensitivity of mammography is decreased in some groups of women, including those with dense breasts [40]. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27].


Female Breast Cancer Screening

Female Breast Cancer Screening. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk. Given the limitations of mammography and to minimize interval cancers, supplemental screening modalities have been investigated in women at average risk. Because screening mammography decreases breast cancer mortality, screening mammography or screening DBT is still performed in women undergoing supplemental screening studies [3,8,35]. Rather than supplementing screening mammography with additional imaging modalities, some have suggested limiting women offered screening mammography based upon individual patient risk assessed by various risk models, breast density, or genetic information such as single-nucleotide polymorphism. However, the randomized controlled trials demonstrating mortality reduction and most large-scale observational studies enrolled women based upon geographic location and age, not other individual patient risk factors. In one observational study in women <50 Female Breast Cancer Screening years of age, restricting screening to women with a first-degree family history, extremely dense breast tissue, or both, would cause 66% of potentially screen-detected cancers to be missed [41]. To maximize the benefits, the ACR recommends screening mammography in average-risk women each year beginning at 40 years of age. Women should continue screening mammography as long as they remain in overall good health and are willing to undergo the examination and subsequent testing or biopsy, if an abnormality is identified [5,8].


Female Breast Cancer Screening

Female Breast Cancer Screening. MRI Breast Without and With IV Contrast Although data are limited regarding the use of breast MRI without and with IV contrast for screening women at average risk, one study has demonstrated that breast MRI demonstrates incremental cancer detection (15-16 cancers per 1,000 breast MRI examinations) over screening mammography with or without screening ultrasound (US) in average-risk women irrespective of breast density [42]. Breast MRI also decreases interval cancers [42,43]. In the DENSE trial, breast MRI significantly reduced interval cancers within women with extremely dense breast tissue and normal mammography, so the European Society of Breast Imaging now recommends screening breast MRI every 2 to 4 years in women 50 to 70 years of age with extremely dense breasts [43,44]. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk. MRI Breast Without and With IV Contrast Abbreviated Data are limited regarding the use of abbreviated breast MRI without and with IV contrast for screening women at average risk. The ECOG-ACRIN abbreviated MRI trial demonstrated a significantly higher CDR for abbreviated breast MRI without and with IV contrast (15 cancers per 1,000) compared with DBT (6 cancers per 1,000), although the study recruited women with dense breasts [45]. In addition to dense breasts, women enrolled in the trial had variable 5 and 10 year risk profiles based upon the Breast Cancer Surveillance Consortium risk calculator and 19% reported 1 or more first degree relatives with breast cancer [45].


Female Breast Cancer Screening

Female Breast Cancer Screening. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI without IV contrast for screening women at average risk. MRI Breast Without IV Contrast Abbreviated There is no relevant literature to support the use of abbreviated MRI without IV contrast for screening women at average risk. Sestamibi MBI Data are limited regarding the use of sestamibi molecular breast imaging (MBI) for screening women at average risk. Most studies have focused upon women with dense breasts and variable risk profiles. One of the larger studies published to date of 1,696 women with recent negative or benign mammographic examinations showed that sestamibi MBI yielded an incremental CDR of 7.7 cancers per 1,000 examinations; however, all 13 cancers were detected in women with dense breasts [46]. Although 92% of the women within the study had <20% estimated lifetime risk, the estimates ranged from 6.1% to 17.2% [46]. Additional retrospective and prospective studies have demonstrated similar incremental CDR for sestamibi MBI of 6.5 to 9 per 1,000 over mammography [40,47]. Female Breast Cancer Screening Sestamibi MBI demonstrates similar sensitivity, better specificity, and lower recall rate compared to supplemental screening US in women with dense breasts [47,48]. US Breast Most studies evaluating the utility of screening with breast US have focused on women with dense breast tissue with or without other risk factors. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27].


Female Breast Cancer Screening

Female Breast Cancer Screening. Screening breast US in women with mammographically dense breasts, including those with risk factors placing them at increased breast cancer risk, identifies mammographically occult, small, node-negative invasive tumors with an increased CDR of 1.8 to 4.6 cancers per 1,000 women screened [40,49]. Although supplemental screening US in women with dense breasts results in an increased CDR, US also increases recall rate, false-positive examinations, and false-positive biopsies [26,49-55]. Data regarding supplemental screening US in average-risk women with nondense breasts is less compelling. In a study of 1,526 average-risk women without mammographic abnormalities, screening with US demonstrated an overall incremental CDR of 3.3 per 1,000, with 5.1 per 1,000 examinations in dense breasts and 0 per 1,000 in nondense breasts compared to digital mammography [56]. In another study of 1,003 average-risk women, US yielded an overall incremental CDR of 3.2 per 1,000 examinations, with 0 per 1,000 in nondense breasts, compared to DBT with or without digital mammography [53]. Digital Breast Tomosynthesis Screening DBT displays reconstructed stacked images of the breast in combination with digital mammographic views, which may be synthetic mammograms reconstructed from the acquired tomosynthesis dataset or FFDM. Compared to FFDM or synthetic mammograms alone, most studies demonstrate that DBT increases CDR and decreases recall rate [14-22]; although, some studies have not reached statistical significance [23] or have found less compelling results in subsets of women, such as those with extremely dense breasts [24,25]. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27].


Female Breast Cancer Screening

Female Breast Cancer Screening. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk. Irrespective of risk category, meta-analyses have demonstrated an incremental increase in CDR of 1.6 to 3.2 per 1,000 screening DBT examinations and a 2.2% pooled decrease in recall rate compared to digital mammography [18,29,30]. The degree of breast cancer mortality reduction from screening mammography varies with different screening regimens. Mortality reduction is greater when screening begins at 40 years of age rather than 45 or 50 years of age Within the limited studies of women at elevated risk due to personal and/or family history of breast cancer, DBT decreased recall rate without a significant increase in CDR compared to FFDM; however, small sample sizes restrict analyses [3,40]. Because screening mammography decreases breast cancer mortality, screening mammography or screening DBT is still performed in women undergoing supplemental screening studies [3,8,35]. The ACR recommends annual screening mammography beginning no later than 40 years of age for women at intermediate risk [3]. For those with a family history of breast cancer, mammography should begin earlier if familial breast cancer occurred at a young age, typically 10 years prior to the youngest age at presentation but generally not before age 30 [6]. For women who have lobular neoplasia or atypical hyperplasia diagnosed prior to 40 years of age, annual screening mammography should be performed from time of diagnosis but generally not prior to 30 years of age [38].


Female Breast Cancer Screening

Female Breast Cancer Screening. Early detection of second breast cancers improves survival, so patients with a personal history of breast cancer should undergo annual mammography or DBT for surveillance following breast conservation therapy [3]. Despite the established mortality benefit, published guidelines differ in their recommendations for screening mammography due to variations in the perceptions of the relative risks and benefits [5,38]. The degree of breast cancer mortality reduction from screening mammography varies with different screening regimens. Mortality reduction is greater when screening begins 40 years of age rather than 45 or 50 years of age and when screening is done more frequently (annually rather than biennially) [8,31]. Annual screening mammography for women 40 to 84 years of age decreases mortality by 40% (12 lives per 1,000 women screened), whereas biennial screening mammography for women 50 to 74 years of age only decreases mortality by 23% (7 lives per 1,000 women screened) [32]. Earlier initiation of screening and more frequent screening result in a greater number of imaging For women 40 to 49 years of age, randomized controlled trials and observational studies demonstrate that screening mammography decreases breast cancer mortality by 15% to 50% [1,8,32,33,39]. Results from the CISNET suggest that annual screening mammography in women 40 to 49 years of age saves 42% more lives and life-years than biennial screening due to faster growing tumors in younger women [31]. Women screened between 40 and 49 years of age are also less likely to require mastectomy or chemotherapy than women diagnosed with palpable tumors [2]. Non-Hispanic black women, Hispanic black, and Hispanic white women have higher breast cancer mortality than non-Hispanic white women, and minority women often present at younger ages with more aggressive tumor subtypes [3,8]. Therefore, decreasing access to screening mammography, especially in women 40 to 49 years of age, may disproportionately impact minority women.


Female Breast Cancer Screening

Female Breast Cancer Screening. Annual screening mammography results in a greater reduction in mortality compared to biennial screening [8]. In women 40 to 84 years of age, annual screening reduces mortality by 40%, compared to a 32% reduction for biennial screening [32]. With regular screening, interval breast cancers do occur with a higher frequency in women undergoing biennial or triennial screening compared to annual screening. The sensitivity of mammography is decreased in some groups of women, including those with dense breasts [40]. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27]. Compared to average breast density (near the threshold between heterogeneously dense and scattered areas of fibroglandular density), the relative risks for developing breast cancer are 1.2 for heterogeneously dense and 2.1 for extremely dense breasts [28]. Some health care providers may therefore consider women with extremely dense breasts to no longer be average risk. Given the limitations of mammography and to minimize interval cancers, supplemental screening modalities have been investigated in women at intermediate risk. Because screening mammography decreases breast cancer mortality, screening mammography or screening DBT is still performed in women undergoing supplemental screening studies [3,8,35]. Rather than supplementing screening mammography with additional imaging modalities, some have suggested limiting women offered screening mammography based upon individual patient risk assessed by various risk models, breast density, or genetic information such as single-nucleotide polymorphisms. However, the randomized controlled trials demonstrating mortality reduction and most large-scale observational studies enrolled women based upon age and geographic location, not individual patient risk factors.


Female Breast Cancer Screening

Female Breast Cancer Screening. In one observational study in women <50 years of age, restricting screening to women with a first-degree family history, extremely dense breast tissue, or both, would cause 66% of potentially screen-detected cancers to be missed [41]. To maximize the benefits, the ACR recommends annual screening mammography beginning no later than 40 years of age for women at intermediate risk [3]. Women should continue screening mammography as long as they remain in overall good health and are willing to undergo the examination and subsequent testing or biopsy, if an abnormality is identified [5,8]. For those with a family history of breast cancer, mammography should begin earlier if familial breast cancer occurred at a young age, typically 10 years prior to the youngest age at presentation but generally not before 30 years of age [6]. For women who have lobular neoplasia or atypical hyperplasia diagnosed prior to 40 years of age, annual screening mammography should be performed from time of diagnosis but generally not prior to 30 years of age [38]. Early detection of second breast cancers improves survival, so patients with a personal history of breast cancer should undergo annual mammography or DBT for surveillance following breast conservation therapy [3]. Mammography With IV Contrast Data are limited regarding the use of mammography with IV contrast for breast cancer screening in intermediate- risk women. To date, published studies have predominantly included women with dense breasts and other risk factors resulting in intermediate- or high-risk profiles. Compared to mammography alone, mammography with IV contrast increases cancer detection (incremental CDR = 6.6-13 per 1,000) in women at elevated risk [57-60]. Female Breast Cancer Screening MRI Breast Without and With IV Contrast MRI has a higher CDR than mammography alone, DBT, or mammography/DBT combined with US [61-64].


Female Breast Cancer Screening

Female Breast Cancer Screening. The incremental CDR of MRI in elevated-risk women ranges from 8 to 29 per 1,000 women, with lower CDR estimates in intermediate-risk women compared to high-risk BRCA mutation carriers [61-63,65,66]. In one study, breast MRI CDR was 15 per 1,000 in women with a prior biopsy demonstrating a high-risk lesion compared to 8 per 1,000 in women reporting a family history [65]. In women with a personal history of breast cancer, a meta-analysis estimated a CDR of 9 to 15 per 1,000 breast MRI [67]. Breast MRI detects small, node-negative invasive cancers at earlier tumor stages compared to mammography, as well as ductal carcinoma in situ [68,69]. Screening MRI also reduces interval cancers [69]. However, breast MRI has a higher recall rate than mammography (15.1% versus 6.4%) [70], higher frequency of BI-RADS category 3 assessment than mammography (14.8% versus 11.8%), and greater frequency of image-guided biopsies than mammography (11.8% versus 2.4%) [63]. MRI Breast Without IV Contrast There is no relevant literature to support the use of breast MRI without IV contrast for screening women at intermediate risk. MRI Breast Without IV Contrast Abbreviated There is no relevant literature to support the use of abbreviated breast MRI without IV contrast for screening women at intermediate risk. Sestamibi MBI Data are limited regarding the use of sestamibi MBI for screening women at intermediate risk. Most studies have focused upon women with dense breasts and variable risk profiles. Retrospective and prospective studies have demonstrated similar incremental CDR for sestamibi MBI of 6.5 to 9 over mammography, with a study demonstrating an incremental CDR of 16.5 per 1,000 in women at increased risk primarily due to family or personal history of breast cancer [40,47]. Sestamibi MBI demonstrates similar sensitivity, better specificity, and lower recall rate compared to supplemental screening US in women with dense breasts [47,48].


Female Breast Cancer Screening

Female Breast Cancer Screening. US Breast Most studies evaluating the utility of screening with breast US have focused on women with dense breast tissue with or without other risk factors. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27]. Screening breast US in women with mammographically dense breasts, including those with risk factors placing them at increased breast cancer risk, identifies predominantly mammographically occult, small, node-negative invasive tumors with an increased CDR of 1.8 to 4.6 cancers per 1,000 women screened [40,49]. Although supplemental screening US in women with dense breasts results in an increased CDR, US also increases recall rate, false-positive examinations, and false-positive biopsies [26,49-55]. In women undergoing annual mammography plus annual supplemental screening MRI, the addition of supplemental screening with US does not identify additional cancers and is therefore not routinely performed. The ACRIN 6666 trial enrolled women with dense breast tissue and at least one other breast cancer risk factor [61]. Compared to mammography alone, screening US detected 5.3 cancers per 1,000 in year 1, 3.7 cancers per 1,000 in years 2 and 3, and resulted in a larger number of false-positive examinations and false-positive biopsies each year [61]. In a prospective study limited to intermediate-risk women, sensitivity of mammography was 57%, US was 24.5%, and mammography combined with biannual US demonstrated 80.4% sensitivity [76]. In women with a Female Breast Cancer Screening personal history of breast cancer, supplemental US screening results in an incremental CDR of 2.4 to 2.9 cancers per 1,000 examinations over mammography alone; however, US screening has lower specificity [10,66].


Female Breast Cancer Screening

Female Breast Cancer Screening. Digital Breast Tomosynthesis Screening DBT displays reconstructed stacked images of the breast in combination with digital mammographic views, which may be synthetic mammograms reconstructed from the acquired tomosynthesis data set or FFDM. Compared to FFDM or synthetic mammograms alone, most studies demonstrate that DBT increases CDR and decreases recall rate [14-22]; although, some studies have not reached statistical significance [23] or have found less compelling results in subsets of women, such as those with extremely dense breasts [24,25]. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27]. Irrespective of risk category, meta-analyses have demonstrated an incremental increase in CDR of 1.6 to 3.2 per 1,000 screening DBT examinations and a 2.2% pooled decrease in recall rate compared to digital mammography [18,29,30]. Within the limited studies of women at elevated risk due to personal and/or family history of breast cancer, DBT decreased recall rate without a significant increase in CDR compared to FFDM; however, small sample sizes restrict analyses [3,40]. High-risk women should begin annual screening mammography at 30 years of age or 10 years prior to the youngest family member who had breast cancer, but generally not before 30 years of age [3]. Approximately one-third of breast cancers may only be detected on mammography in BRCA2 mutation carriers who are <40 years of age [79]. In some mutation carriers, some referring providers use mammography or DBT beginning at 40 years of age if patients undergo annual MRI [80]. Women who underwent thoracic or upper abdominal radiation therapy at an early age (<30 years) should begin screening mammography 8 years after radiation therapy but not before 25 years of age [3]. Because screening mammography decreases breast cancer mortality, screening mammography or screening DBT is still performed in women undergoing supplemental screening studies [3,8,35].


Female Breast Cancer Screening

Female Breast Cancer Screening. Mammography Screening To date, mammography is the only screening modality shown to decrease breast cancer mortality. Multiple randomized controlled trials demonstrate that invitation to screening mammography results in at least a 22% Female Breast Cancer Screening For women 40 to 49 years of age, randomized controlled trials and observational studies demonstrate that screening mammography decreases breast cancer mortality by 15% to 50% [1,8,32,33,39]. Results from the CISNET suggest that annual screening mammography in women 40 to 49 years of age saves 42% more lives and life-years than biennial screening due to faster growing tumors in younger women [31]. Women screened between 40 and 49 years of age are also less likely to require mastectomy or chemotherapy than women diagnosed with palpable tumors [2]. Non-Hispanic Black, Hispanic Black, and Hispanic White women have higher breast cancer mortality than non- Hispanic White women, and minority women often present at younger ages with more aggressive tumor subtypes [3,8]. Therefore, decreasing access to screening mammography, especially in women 40 to 49 years of age, may disproportionately impact minority women. Annual screening mammography results in a greater reduction in mortality compared to biennial screening [8]. In women 40 to 84 years of age, annual screening reduces mortality by 40%, compared to a 32% reduction for biennial screening [32]. With regular screening, interval breast cancers do occur with a higher frequency in women undergoing biennial or triennial screening compared to annual screening. The sensitivity of mammography is decreased in some groups of women, including those with dense breasts [40]. Dense breast tissue decreases the sensitivity of mammography [26] and is an independent risk factor for developing breast cancer [27]. Given the limitations of mammography and to minimize interval cancers, supplemental screening modalities have been investigated in women at high risk.


Female Breast Cancer Screening

Female Breast Cancer Screening. Because screening mammography decreases breast cancer mortality, screening Female Breast Cancer Screening mammography or screening DBT is still performed in women undergoing supplemental screening studies [3,8,35]. Rather than supplementing screening mammography with additional imaging modalities, some have suggested limiting women offered screening mammography based upon individual patient risk assessed by various risk models, breast density, or genetic information such as single-nucleotide polymorphism. However, the randomized controlled trials demonstrating mortality reduction and most large-scale observational studies enrolled women based upon age and geographic location, not individual patient risk factors. In one observational study in women <50 years of age, restricting screening to women with a first-degree family history, extremely dense breast tissue, or both, would cause 66% of potentially screen-detected cancers to be missed [41]. Numerous studies in high-risk women have evaluated the performance of mammography and supplemental screening modalities, such as US and MRI. Mammography consistently demonstrates lower sensitivity (25%-69%) than US or MRI, and high-risk women experience higher interval cancer rates than the general population [3,40]. The combination of mammography with MRI yields the highest sensitivity across high-risk groups of women (91%- 98%) [3,40,81]. Because screening mammography decreases breast cancer mortality, screening mammography or screening DBT is still performed in women undergoing supplemental screening studies [3,8,35]. High-risk women should begin annual screening mammography at 30 years of age or 10 years prior to the youngest family member who had breast cancer, but generally not before 30 years of age [3]. Approximately one-third of breast cancers may only be detected on mammography in BRCA2 mutation carriers who are <40 years of age [79].


Female Breast Cancer Screening

Female Breast Cancer Screening. In some mutation carriers, some referring providers use mammography or DBT beginning at 40 years of age if patients undergo annual MRI [80]. Women who underwent thoracic or upper abdominal radiation therapy at an early age (<30 years) should begin screening mammography 8 years after radiation therapy but not before 25 years of age [3]. Mammography With IV Contrast Data are limited regarding the use of mammography with IV contrast for breast cancer screening in high-risk women. To date, published studies have predominantly included women with dense breasts and other risk factors resulting in intermediate or high-risk profiles. Compared to mammography alone, mammography with IV contrast increases sensitivity and cancer detection (incremental CDR = 6.6-13 per 1,000) in women at elevated risk [57-60]. Mammography with IV contrast may be useful in high-risk women as an alternative to MRI. MRI Breast Without and With IV Contrast MRI has a higher CDR than mammography alone, DBT, or mammography/DBT combined with US [61-64]. In high-risk women, supplemental screening MRI combined with mammography yields a 91% to 98% sensitivity, although the reported specificity of MRI is typically lower than mammography [40,81]. The incremental CDR of MRI in elevated-risk women ranges from 8 to 29 per 1,000 women, with higher CDR (26 per 1,000) in BRCA mutation carriers [61-63,65,66]. Breast MRI detects small, node-negative invasive cancers at earlier tumor stages compared to mammography, as well as ductal carcinoma in situ [68,69]. Screening MRI also reduces interval cancers [69]. However, breast MRI has a higher recall rate than mammography (15.1% versus 6.4%) [70], higher frequency of BI-RADS category 3 assessment than mammography (14.8% versus 11.8%), and a greater frequency of image-guided biopsies than mammography (11.8 versus 2.4%) [63]. Since 2007, the American Cancer Society has recommended annual breast MRI for breast cancer screening in high- risk women [4].


Female Breast Cancer Screening

Female Breast Cancer Screening. The ACR recommends annual breast MRI in high-risk women beginning as early as 25 years of age [3]. Female Breast Cancer Screening MRI Breast Without and With IV Contrast Abbreviated Data are limited regarding the use of abbreviated breast MRI without and with IV contrast for screening in high- risk women. Following the publication of the American Cancer Society guidelines for supplemental screening breast MRI in 2007, high-risk women have traditionally undergone conventional full protocol breast MRI without and with IV contrast [3,4]. However, multiple studies have demonstrated similar diagnostic accuracy for abbreviated protocol MRI compared to conventional full protocol breast MRI [73-75]. In a study evaluating 3,037 abbreviated breast MRI in 1,975 high-risk women, the CDR was 29 per 1,000, the interval cancer rate was 0.66 per 1,000, and all cancers missed by abbreviated breast MRI were node negative early-stage invasive malignancies [72]. MRI Breast Without IV Contrast There is no relevant literature to support the use of MRI without IV contrast for screening women at high risk. MRI Breast Without IV Contrast Abbreviated There is no relevant literature to support the use of abbreviated breast MRI without IV contrast for screening women at high risk. Sestamibi MBI Data are limited regarding the use of sestamibi MBI for screening women at high risk. Most studies have focused upon women with dense breasts and variable risk profiles. Retrospective and prospective studies have demonstrated similar incremental CDR for sestamibi MBI of 6.5 to 9 over mammography, with one study demonstrating an incremental CDR of 16.5 per 1,000 in women at increased risk primarily due to family or personal history of breast cancer [40,47]. Sestamibi MBI demonstrates similar sensitivity, better specificity, and lower recall rate compared to supplemental screening US in women with dense breasts [47,48].


Female Breast Cancer Screening

Female Breast Cancer Screening. US Breast In high-risk women undergoing annual mammography plus annual supplemental screening MRI, the addition of supplemental screening with US does not identify additional cancers and is therefore not routinely performed. Screening US may be useful in high-risk patients as an alternative to MRI. However, high-risk women who do not undergo supplemental screening MRI should be counseled that the CDR of US is inferior to MRI. MRI has a higher CDR than mammography, DBT, or mammography/DBT combined with US [61-64]. The ACRIN 6666 trial enrolled women with elevated breast cancer risk [61]. Compared to mammography alone, screening US detected 5.3 cancers per 1,000 in year 1 and 3.7 cancers per 1,000 in years 2 and 3 and resulted in a larger number of false- positive examinations and false-positive biopsies each year [61]. After 3 consecutive rounds of mammography plus US, the incremental CDR of MRI was 14.7 per 1,000, although false-positive examinations also increased [61]. In a prospective multicenter study of 687 high-risk women who underwent clinical breast examination, mammography, US, and MRI for screening, the combination of MRI plus mammography maximized the breast cancers detected [62]. Mammography identified 5 cancers per 1,000 compared to 6 per 1,000 for US, 7.7 per 1,000 for mammography plus US, 14.9 per 1,000 for MRI, 14.9 per 1,000 for MRI plus US, 16 per 1,000 for mammography plus MRI, and 16 per 1,000 for mammography plus US plus MRI [62]. In a prospective study of BRCA mutation carriers and high-risk women, sensitivity of mammography was 25% and 66% whereas US was 23% and 34%, respectively [76]. In the high-risk group, mammography combined with biannual US demonstrated 100% sensitivity [76]; however, MRI was not performed. In a subset analysis of BRCA mutation carriers, MRI sensitivity was 94% [76]. In another study of 529 high-risk women suspected or proven to carry a deleterious BRCA mutation, the performance of US was also inferior to MRI [82].


Staging and Follow up of Primary Vaginal Cancer.  Introduction/Background Primary vaginal cancer is rare, comprising 1% to 2% of gynecologic malignancies and 20% of all malignancies involving the vagina [1,2]. More frequently, the vagina is involved secondarily either by direct invasion from malignancies originating in adjacent organs, most commonly the cervix or vulva, or by metastases from other pelvic or extrapelvic primary malignancies [1,2]. Additionally, any vaginal tumor involving the cervix or vulva, whether or not the lesion is centered in the vagina, is classified by the International Federation of Gynecology and Obstetrics (FIGO) system as a primary cervical or vulvar cancer, respectively. Squamous cell carcinoma is the most common underlying histology in primary vaginal cancer, representing 80% to 90% of primary vaginal cancer [3] and occurs most frequently in postmenopausal women, with adenocarcinoma representing around 5% to 10% of cases and even rarer histologies such as sarcoma, melanoma, and lymphoma accounting for the remainder [1,2]. Primary vaginal cancer is staged according to two systems, FIGO and the American Joint Committee on Cancer (AJCC). FIGO stipulates a clinical staging paradigm, whereby features derived from bimanual and/or rectovaginal examination, cystoscopy, proctoscopy, and radiography are permissible for incorporation into staging [4]. Although FIGO encourages the use of advanced imaging modalities such as CT, MRI, and PET to guide management, information derived from these examinations does not alter the formal clinical FIGO stage [4]. Given the rarity of primary vaginal cancer, treatment principles are derived from retrospective data in addition to extrapolation from more established management paradigms for cervical and anal squamous cell cancers. Surgical management for vaginal cancer is limited primarily to small (<2 cm) early stage lesions, with larger lesions posing greater difficultly for achieving negative surgical margins.


Staging and Follow up of Primary Vaginal Cancer. Although surgical options exist for locally advanced disease, they often involve a degree of pelvic exenteration and therefore confer substantial morbidity. For this reason, the management paradigm for locally advanced disease has largely trended toward definitive radiation therapy with concurrent chemotherapy [1,5]. Though data on the use of imaging in vaginal cancer are sparse, insights derived from the study of imaging in cervical cancer have reasonable generalizability to vaginal cancer because of similar tumor biology. Moreover, given the trend toward definitive chemoradiation for both cancers in all but early stage lesions, principles of postchemoradiation the recommendations outlined in this document are informed by principles translated from the literature on cervical cancer. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: publications@acr.org Staging and Follow-up of Primary Vaginal Cancer imaging in initial and adaptive radiation planning for vaginal cancer is not specifically addressed in this document, and analogous principles for cervical cancer are covered in extensive detail elsewhere [6]. OR Discussion of Procedures by Variant Variant 1: Vaginal cancer. Pretreatment staging. Initial imaging. Although the 2009 FIGO staging system for vaginal cancer indicates that findings on advanced imaging (CT, MRI, PET/CT) should not modify stage designation [4], such imaging findings are routinely employed in clinical practice to prognosticate and guide management decisions in patients with vaginal cancer.


Staging and Follow up of Primary Vaginal Cancer. Recent updates to the FIGO staging system for cervical cancer, which incorporate advanced imaging results into staging [10], reflect the wide recognition that cross-sectional imaging provides actionable staging information not readily obtained by physical examination or conventional radiography. Moreover, the increasing use of definitive radiotherapy across all stages of vaginal cancer obligates the incorporation of advanced imaging into pretreatment evaluation, because it is essential for treatment planning. The rationale for optimizing staging accuracy in vaginal cancer, in part via the inclusion of cross-sectional imaging, is multifold. First, accurate initial staging is fundamental to prognostication [11], facilitating incorporation of expectations of treatment efficacy into goals of care. Second, proper initial staging permits selection of the most appropriate treatment based on extent of disease. Regarding local extent, for vaginal lesions deemed likely confined to the vaginal wall (stage I) based on clinical examination, exclusion of extravaginal invasion with further testing is essential for ensuring that planned definitive surgery is likely to achieve a disease-free margin or that a radiation field properly incorporates the tumor volume. Regional nodal metastases include pelvic nodal metastases, which are primarily detected with cross-sectional imaging, and inguinal nodes (in lower vaginal cancers), a subset of which can be identified on clinical examination. Pretreatment knowledge of suspicious nodes may impact the decision to pursue surgery versus radiation. In addition, the distribution of suspicious nodes has the potential to influence radiation-specific factors such as field and dose planning, including possible node-directed boost doses as employed in cervical cancer [12].


Staging and Follow up of Primary Vaginal Cancer. Regarding distant metastases, detection of extraregional nodal or solid organ lesions can obviate unnecessarily morbid radical pelvic surgery and instead direct care toward palliative regimens or radiotherapy with an extended field. Finally, the ability to accurately stage noninvasively can avoid the need for invasive staging procedures such as cystoscopy (for bladder mucosal invasion) and proctoscopy (for rectal mucosal invasion), both of which are historical components of the FIGO clinical staging system [1]. CT Chest Although thoracic metastases are known to occur in vaginal cancer, no studies specifically address their incidence or the incremental value of chest CT for initial staging. Pulmonary metastases have been studied to a limited degree in cervical cancer, occurring in approximately 5% to 10% of patients at diagnosis [13,14]. Pulmonary metastases appear to occur slightly more frequently as a site of recurrent disease, with one large study of recurrent cervical cancer indicating an overall incidence of 13%, and the lungs representing the only site of recurrence in 6% of cases [15]. In studies evaluating pulmonary metastases from cervical cancer, chest CT was the most frequent diagnostic modality employed, with the vast majority of patients asymptomatic at the time of imaging [16,17]. These findings support the use of chest CT with or without intravenous (IV) contrast in the early posttreatment evaluation of cervical cancer, as endorsed by the National Comprehensive Cancer Network (NCCN) guidelines, and suggest that a similar strategy would be useful for vaginal cancer. Staging and Follow-up of Primary Vaginal Cancer CT Abdomen and Pelvis Data on the diagnostic performance of CT in primary vaginal cancer staging are very limited.


Staging and Follow up of Primary Vaginal Cancer. A small retrospective study evaluating fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT in 23 patients with primary vaginal cancer found that CT and FDG-PET detected pelvic nodal metastases in 17% (4 of 23) and 35% (8 of 23) of patients, respectively, suggesting inferior sensitivity of CT alone [18]. CT has been studied more extensively in cervical cancer staging, with available data comparing CT to MRI for local staging and CT (with or without IV contrast) to PET for regional and distant staging. For local staging, the ACRIN 6651 study showed that CT and MRI had sensitivity of 42% and 53%, respectively, and specificity of 82% and 75%, respectively, for classifying disease as stage IIB (parametrial invasion) or higher, with none of these differences reaching statistical significance [19]. However, a more recent meta-analysis suggested improved performance of MRI for parametrial invasion with modern hardware (sensitivity 76%, specificity 94%), particularly when the field strength was 3T and diffusion-weighted imaging was included [20], whereas a recent study of multidetector CT showed only 50% sensitivity for parametrial invasion [21]. Although older literature suggested lower sensitivity of CT compared with FDG-PET/CT for nodal metastases [22], the more recent ACRIN 6671/Gynecology Oncology Group (GOG) 0233 trial demonstrated a more modest difference in sensitivity for abdominal nodes (42% versus 50%, respectively) [23]. Likewise, in a recent meta- analysis, CT had only modestly lower area under the curve (AUC) (0.83) compared with PET/CT (0.90) for detection of nodal metastases from cervical cancer [24]. For distant metastases from cervical cancer, CT is inferior in the detection of osseous metastases (sensitivity 66%) compared with FDG-PET/CT (sensitivity 96%) [25].


Staging and Follow up of Primary Vaginal Cancer. These findings, if applied to vaginal cancer, suggest that modern multidetector CT abdomen and pelvis is a reasonable staging tool for regional and distant metastases, although is likely inferior to MRI for local staging, modestly inferior to FDG-PET/CT for nodal metastases, and inferior to FDG-PET/CT for osseous metastases. The use of IV contrast is strongly encouraged when possible, because the improved tissue contrast likely benefits primary tumor evaluation, delineation of lymph nodes from adjacent vessels, and detection of hepatic metastases. No studies have specifically evaluated the performance of CT of the abdomen and pelvis without IV contrast for vaginal cancer staging. FDG-PET/CT Skull Base to Mid-Thigh Data regarding the diagnostic performance of PET/CT for initial staging in patients with vaginal cancer are limited. Lamoreaux et al [18], in a prospective study, evaluated the comparative performance of PET versus CT in 23 patients with primary vaginal cancer prior to treatment. PET identified suspicious pelvic and/or groin lymph nodes in 35% (8 of 23) of patients, whereas CT did so in only 17% (4 of 23) of patients, although a pathologic reference standard was present in only two sampled groin nodes. No patient had extrapelvic nodal or distant disease, limiting the applicability of this study to metastases outside of the pelvis. Although data are limited for primary vaginal cancer staging, a growing body of literature supports the role of FDG- PET/CT in the initial staging of cervical cancer. Prospective data from the ACRIN 6671/GOG 0233 trial suggested, with borderline statistical significance, that FDG-PET/CT is more sensitive than CT alone for extrapelvic nodal metastases in cervical cancer (50% versus 42%, respectively), with similar specificity (85% versus 89%, respectively) [23], supporting prior retrospective data [22].


Staging and Follow up of Primary Vaginal Cancer. FDG-PET/CT is also more sensitive than conventional CT for osseous metastases [25], with sensitivity and specificity of 55% and 98%, respectively, for all distant metastases [13]. Accordingly, the NCCN guidelines endorse preference for whole-body FDG-PET/CT over conventional CT for initial staging of all cervical cancer designated stage II and above, with either FDG-PET/CT or conventional CT recommended in stage I disease [27]. Staging and Follow-up of Primary Vaginal Cancer Fluoroscopy Contrast Enema There is no relevant literature regarding the use of fluoroscopic contrast enema in the modern imaging workup of vaginal cancer, and its use has largely been replaced by cross-sectional imaging techniques. MRI Pelvis Because of the rarity of vaginal cancer, the primary data regarding the use of MRI in initial staging of vaginal cancer are sparse. Taylor et al [28] retrospectively evaluated pelvic MRI for initial staging in 25 patients with primary vaginal cancer spanning all disease stages. MRI depicted the primary tumor in 96% (24 of 25) of patients, demonstrating hyperintense signal compared to muscle on T2-weighted images, and enabled assignment of a radiologic disease stage based on adaptation of FIGO clinical staging criteria. Because 80% (20 of 25) of patients received either radiation or palliative therapy, pathologic confirmation of imaging findings could be obtained in only 20% (5 of 25) of cases. Of these cases, MRI stage was concordant with pathologic stage in 40% (2 of 5) of the cases. More recent data in cervical cancer patients support the use of MRI for initial staging, with a meta-analysis suggesting high sensitivity (76%) and specificity (94%) of MRI for parametrial invasion [20]. Although MRI readily depicts lymph nodes, it has constraints similar to CT with regard to the limited sensitivity and specificity of size and morphologic criteria. No study has specifically evaluated the performance of MRI for pretreatment nodal staging in vaginal cancer.


Staging and Follow up of Primary Vaginal Cancer. However, data from mixed cohorts of patients with recurrence of cervical, vaginal, and other gynecologic cancers have suggested superior sensitivity of FDG-PET/CT for pelvic nodal metastases compared with pelvic MRI and CT [29,30]. The use of IV contrast may improve tissue characterization but is not considered essential, with variable inclusion in published protocols for evaluation of vaginal [28,31] and cervical cancer [7,32-34]. No study has specifically compared the incremental utility of contrast-enhanced sequences over T2-weighted sequences for pelvic MRI in this context. Regarding the use of vaginal gel in MRI of the pelvis, there is insufficient primary data in the literature to support its routine use. MRI Abdomen and Pelvis Because of the rarity of vaginal cancer, the primary data regarding the use of MRI in initial staging of vaginal cancer are sparse. Taylor et al [28] retrospectively evaluated pelvic MRI for initial staging in 25 patients with primary vaginal cancer spanning all disease stages. MRI depicted the primary tumor in 96% (24 of 25) of patients, demonstrating hyperintense signal compared to muscle on T2-weighted images, and enabled assignment of a radiologic disease stage based on adaptation of FIGO clinical staging criteria. Because 80% (20 of 25) of patients received either radiation or palliative therapy, pathologic confirmation of imaging findings could be obtained in only 20% (5 of 25) of cases. Of these cases, MRI stage was concordant with pathologic stage in 40% (2 of 5). More recent data in cervical cancer patients support the use of MRI for initial staging, with a meta-analysis suggesting high sensitivity (76%) and specificity (94%) of MRI for parametrial invasion [20]. Although MRI readily depicts lymph nodes, it has constraints similar to CT with regard to the limited sensitivity and specificity of size and morphologic criteria.


Staging and Follow up of Primary Vaginal Cancer. No study has specifically evaluated the performance of MRI for pretreatment nodal staging in vaginal cancer. However, data from mixed cohorts of patients with recurrence of cervical, vaginal, and other gynecologic cancers have suggested superior sensitivity of FDG-PET/CT for pelvic nodal metastases compared with pelvic MRI and CT [29,30]. If MRI of the abdomen and pelvis is used in place of CT of the abdomen and pelvis, the addition of chest CT is encouraged to evaluate for pulmonary metastases. The use of IV contrast may improve tissue characterization and is particularly beneficial when MRI of the abdomen is included, because it improves detection of hepatic metastases. Radiography Intravenous Urography There is no relevant literature regarding the use of radiographic IV urography in the modern imaging workup of vaginal cancer, and its use has largely been replaced by cross-sectional imaging techniques. US Abdomen and Pelvis Transabdominal There is no relevant literature regarding the role of transabdominal abdominopelvic (TA) US in vaginal cancer staging. TAUS is inferior for visualizing the female genital tract compared with TVUS, and neither technique has a role in the evaluation of regional or distant disease. Variant 2: Posttreatment evaluation of vaginal cancer. No suspected recurrence. Initial imaging. As the use of definitive chemoradiation for the treatment of primary vaginal cancer has grown, so too has the role of cross-imaging for assessment of treatment response. In contrast to extirpative surgery, in which pathologic margin assessment can confirm removal of viable tumor, evaluation for tumor eradication following chemoradiation relies in part on imaging assessment. Much of the support for the value of early posttreatment imaging in primary vaginal cancer is extrapolated from the large body of literature on cervical cancer, for which the treatment paradigm and endpoints are analogous.


Staging and Follow up of Primary Vaginal Cancer. Early posttreatment imaging is performed most commonly following a period of approximately 3 to 6 months after the completion of chemoradiation. Some centers also image during therapy for early response assessment and/or adaptive radiation planning [7]. The goals of early posttreatment imaging are multiple. First, imaging response after chemoradiation is a potent predictor of oncologic outcome, therefore providing crucial prognostic data [40-42]. Second, the degree of imaging response directly informs therapeutic decision-making, because persistent or progressive disease following chemoradiation requires salvage therapy [40]. For persistent pelvic disease, options include salvage radical surgery or less commonly reirradiation. Detection of new distant disease following initial treatment obviates curative surgery and may direct therapy toward chemotherapeutic and/or palliative options. Finally, the degree of response can influence the frequency of subsequent surveillance, with complete response enabling more conservative follow- up testing [42]. Following complete response, there is no formally established role for routine surveillance imaging in asymptomatic patients treated for vaginal cancer nor has a role been established for cervical cancer. Guidelines generally advocate for routine clinical examination for surveillance in asymptomatic patients, with imaging suggested in the setting of symptoms or abnormal physical examination findings [43]. CT Chest Although thoracic metastases are known to occur in vaginal cancer, no studies specifically address their incidence or the incremental value of chest CT in early posttreatment evaluation. Pulmonary metastases have been studied to a limited degree in cervical cancer, occurring in approximately 5% to 10% of patients at diagnosis [13,14].


Staging and Follow up of Primary Vaginal Cancer. Pulmonary metastases appear to occur slightly more frequently as a site of recurrent disease, with one large study of recurrent cervical cancer indicating an overall incidence of 13%, and the lungs representing the only site of recurrence in 6% of cases [15]. Moreover, the lungs can uncommonly represent a site of distant disease that newly arises following definitive chemoradiation for disease that was initially locoregional [41]. In studies evaluating pulmonary metastases from cervical cancer, chest CT was the most frequent diagnostic modality employed, with the vast majority of patients asymptomatic at the time of imaging [16,17]. These findings support the use of chest CT with or without IV contrast in the early posttreatment evaluation of cervical cancer, as endorsed by the NCCN guidelines, and suggest that a similar strategy would be useful for vaginal cancer. CT Abdomen and Pelvis For detection of residual primary tumor after chemoradiation, CT alone is likely inferior compared with FDG- PET/CT and pelvic MRI based on extrapolation from data on comparative imaging performance in the pretreatment evaluation of cervical cancer [21,44]. CT lacks the tissue contrast of MRI and the metabolic data of FDG-PET, both of which are useful in deciphering posttreatment changes from residual disease. Because CT relies primarily on size criteria for nodal evaluation, it has limitations similar to MRI with respect to sensitivity and specificity for nodal metastases. Therefore, although CT may depict size regression of nodal metastases following therapy, it is likely at least modestly inferior for detecting new or residual disease in subcentimeter lymph nodes compared with FDG- PET/CT [22,23,29,30].


Staging and Follow up of Primary Vaginal Cancer. Staging and Follow-up of Primary Vaginal Cancer CT of the abdomen and pelvis is not commonly performed in the absence of chest CT, given that the lungs are a potential site of distant disease that may newly arise in patients who have undergone definitive chemoradiation for disease that was initially locoregional [41]. Importantly, CT alone is inferior to FDG/PET-CT for evaluation of distant disease in the bones [25] and modestly inferior for nodal assessment [23,41]. The use of IV contrast is strongly encouraged when possible, because the improved tissue contrast likely benefits primary tumor evaluation, delineation of lymph nodes from adjacent vessels, and detection of hepatic metastases. No studies have specifically assessed the performance of CT of the abdomen and pelvis without IV contrast for posttreatment evaluation of primary vaginal cancer. FDG-PET/CT Skull Base to Mid-Thigh Although data in primary vaginal cancer patients are limited, studies substantiating its treatment response assessment role in cervical cancer are numerous. In one prospective study in cervical cancer patients treated with definitive chemoradiation, FDG-PET/CT responses classified as complete metabolic response (absence of abnormal uptake at prior sites of disease), partial metabolic response and progressive disease at a mean of 3 months after therapy correlated closely with prognosis, with 3 year progression-free survival of 78%, 33%, and 0%, respectively [40]. In another prospective study, 9% (5 of 55) of patients developed new distant disease at the time of a posttreatment FDG-PET/CT scan, underscoring the value of whole-body imaging rather than pelvic-only imaging at the time of response evaluation [41]. Accordingly, the NCCN guidelines for cervical cancer recommend whole- body FDG-PET/CT at 3 to 6 months after completion of definitive therapy for disease stages II to IV, because it directly informs prognosis, therapy, and intensity of surveillance [27].


Staging and Follow up of Primary Vaginal Cancer. Fluoroscopy Contrast Enema There is no relevant literature regarding the use of fluoroscopic contrast enema in the modern imaging workup of vaginal cancer, and its use has largely been replaced by cross-sectional imaging techniques. MRI Pelvis Although no study has specifically evaluated pelvic MRI for treatment response assessment in vaginal cancer patients, multiple studies support its potential value in cervical cancer to which analogous principles apply. Following successful therapy with chemoradiation, the initially intermediate to high-signal-intensity tumor on T2- weighted images decreases in both size and signal intensity, with eventual conversion to low-signal-intensity fibrotic tissue [7,31]. However, the main limitation of MRI in the very early posttreatment period (<2 months after completion) is its difficulty distinguishing early postradiation change from residual tumor, both of which can demonstrate intermediate- to high-signal T2-weighted intensity and avid gadolinium enhancement [33,34]. One retrospective study evaluating pelvic MRI at a median of 5 weeks after completion of chemoradiation for cervical cancer found that 37% (16 of 44) of MRI examinations were considered indeterminate for discriminating residual disease and fibrosis [34]. Despite diagnostic confidence in the remainder of cases, sensitivity and specificity for residual disease were 80% and 55%, respectively, indicating a high false-positive rate because of posttreatment change. A more recent retrospective study in cervical cancer patients found better performance of pelvic MRI at a later postchemoradiation time point (median 9 weeks) with strict objective diagnostic criteria, achieving sensitivity and specificity of 91% and 85%, respectively, for residual disease [33].


Staging and Follow up of Primary Vaginal Cancer. Therefore, for cervical cancer, the suggested time interval for determining posttherapy treatment response with pelvic MRI is 3 to 6 months after completion of therapy [27], although earlier imaging is sometimes used for interim assessment of tumor regression for prognostication and/or adaptive radiation planning. Because MRI relies primarily on size criteria for nodal evaluation, it has limitations similar to CT with respect to sensitivity and specificity for nodal metastases. Therefore, although MRI may depict size regression of nodal metastases following therapy, it is likely at least modestly inferior for detecting new or residual disease in subcentimeter lymph nodes compared to FDG-PET/CT [22,23,29,30]. The use of IV contrast may improve tissue characterization but is not considered essential, with variable inclusion in published protocols for evaluation of vaginal [28,31] and cervical cancer [7,32-34]. No study has specifically compared the incremental utility of gadolinium-enhanced sequences over T2-weighted sequences for pelvic MRI in this context. Regarding the use of vaginal gel in MRI of the pelvis, there is insufficient primary data in the literature to support its routine use. MRI Abdomen and Pelvis MRI of the abdomen and pelvis can be considered in the early posttreatment evaluation of primary vaginal cancer, although its main value is in the utility of pelvic MRI for primary tumor response assessment. MRI of the abdomen is not commonly included, given the availability of whole-body FDG-PET/CT or CT of the chest, abdomen, and Staging and Follow-up of Primary Vaginal Cancer pelvis for evaluation of distant disease. Although no study has specifically evaluated pelvic MRI for treatment response assessment in vaginal cancer patients, multiple studies support its potential value in cervical cancer to which analogous principles apply.


Staging and Follow up of Primary Vaginal Cancer. Following successful therapy with chemoradiation, the initially intermediate- to high-signal-intensity tumor on T2-weighted images decreases in both size and signal intensity, with eventual conversion to low-signal-intensity fibrotic tissue [7,31]. However, the main limitation of MRI in the very early posttreatment period (<2 months after completion) is its difficulty distinguishing early postradiation change from residual tumor, both of which can demonstrate intermediate- to high-signal T2-weighted intensity and avid gadolinium enhancement [33,34]. One retrospective study evaluating pelvic MRI at a median of 5 weeks after completion of chemoradiation for cervical cancer found that 37% (16 of 44) of MRI examinations were considered indeterminate for discriminating residual disease and fibrosis [34]. Despite diagnostic confidence in the remainder of cases, sensitivity and specificity for residual disease were 80% and 55%, respectively, indicating a high false-positive rate because of posttreatment change. A more recent retrospective study in cervical cancer patients found better performance of pelvic MRI at a later postchemoradiation time point (median 9 weeks) with strict objective diagnostic criteria, achieving sensitivity and specificity of 91% and 85%, respectively, for residual disease [33]. Therefore, for cervical cancer, the suggested time interval for determining posttherapy treatment response with pelvic MRI is 3 to 6 months after completion of therapy [27], although earlier imaging is sometimes used for interim assessment of tumor regression for prognostication and/or adaptive radiation planning. Because MRI relies primarily on size criteria for nodal evaluation, it has limitations similar to CT with respect to sensitivity and specificity for nodal metastases.


Staging and Follow up of Primary Vaginal Cancer. Therefore, although MRI may depict size regression of nodal metastases following therapy, it is likely at least modestly inferior for detecting new or residual disease in subcentimeter lymph nodes compared to FDG-PET/CT [22,23,29,30]. If MRI of the abdomen and pelvis is used in place of CT of the abdomen and pelvis, the addition of chest CT is encouraged to evaluate for pulmonary metastases. The use of IV contrast may improve tissue characterization and should be used especially when MRI of the abdomen is included, because it improves detection of hepatic metastases. Radiography Intravenous Urography There is no relevant literature regarding the use of radiographic IV urography in the modern imaging workup of vaginal cancer, and its use has largely been replaced by cross-sectional imaging techniques. US Abdomen and Pelvis Transabdominal There is no relevant literature regarding the role of TAUS in vaginal cancer staging. TAUS is inferior for visualizing the female genital tract compared with TVUS, and neither technique has a role in nodal or distant evaluation. US Pelvis Transvaginal There is no relevant literature regarding the role of TVUS in the early posttreatment evaluation of primary vaginal cancer. Limited studies in cervical cancer patients have evaluated the use of color and/or power Doppler US for detecting changes in tumor vascularity as a marker of treatment response [45]. However, the applicability of these findings to clinical practice remains unclear. The NCCN guidelines do not currently endorse the use of TVUS for early posttreatment evaluation in cervical cancer, and its role in vaginal cancer remains undefined. Additionally, TVUS has limited utility for pelvic nodal evaluation [39]. Variant 3: Vaginal cancer. Suspected or known recurrence. Evaluate extent of disease. Initial imaging.


Staging and Follow up of Primary Vaginal Cancer. Cross-sectional imaging plays a crucial role in the evaluation of patients with known or suspected vaginal cancer recurrence, in which physical examination is of limited value in determining disease extent. In one retrospective study of patients with primary vaginal cancer who underwent definitive radiation and experienced recurrence, the mechanism of recurrence was locoregional alone in 56% for disease stages I and II and 71% for disease stages III to IVA, whereas the remainder of recurrences were distant [46]. Once locoregional recurrence is identified, the presence or absence of distant recurrence becomes a discriminating factor in eligibility for salvage pelvic exenteration. In the presence of distant recurrence, exenteration confers morbidity without significantly improving oncologic outcomes, whereas in the absence of distant recurrence, exenteration can potentially eradicate pelvic tumor burden. When distant disease has been excluded by imaging and a patient is deemed eligible for pelvic exenteration, the degree of local organ invasion determines whether partial (anterior or posterior) or total exenteration is indicated [32]. Therefore, imaging findings in patients with known or suspected vaginal cancer recurrence can influence both the appropriateness and type of salvage therapy, in addition to predicting prognosis. Staging and Follow-up of Primary Vaginal Cancer CT Chest Although thoracic metastases are known to occur in vaginal cancer, no studies specifically address their incidence or the incremental value of chest CT for suspected recurrence. Pulmonary metastases have been studied to a limited degree in cervical cancer, occurring in approximately 5% to 10% of patients at diagnosis [13,14]. Pulmonary metastases appear to occur slightly more frequently as a site of recurrent disease, with one large study of recurrent cervical cancer indicating an overall incidence of 13% and the lungs representing the only site of recurrence in 6% of cases [15].


Staging and Follow up of Primary Vaginal Cancer. In studies evaluating pulmonary metastases from cervical cancer, chest CT was the most frequent diagnostic modality employed, with the vast majority of patients asymptomatic at the time of imaging [16,17]. These findings support the use of chest CT with or without IV contrast in the early posttreatment evaluation of cervical cancer, as endorsed by the NCCN guidelines, and suggest that a similar strategy would be useful for vaginal cancer. CT Abdomen and Pelvis Data on the diagnostic performance of CT in known or suspected recurrence of vaginal cancer are very limited, requiring extrapolation from pretreatment vaginal cancer cohorts as well as cohorts of patients with other gynecologic malignancies. Regarding local extent evaluation, the prospective ACRIN 6651 study of patients with cervical cancer prior to treatment, found that CT was insensitive for detection of rectal and bladder invasion, suggesting that performance would be similarly poor in the setting of recurrent disease prior to pelvic exenteration [19]. A small retrospective study evaluating FDG-PET/CT in 23 patients with primary vaginal cancer prior to treatment found that CT and FDG-PET detected pelvic nodal metastases in 17% (4 of 23) and 35% (8 of 23) of patients, respectively, suggesting inferior sensitivity of CT alone for nodal metastases. Although older literature suggested that CT is less sensitive than PET/CT for nodal metastases [22], the more recent ACRIN 6671/GOG 0233 trial in cervical cancer patients prior to treatment showed a more modest difference in sensitivity for abdominal nodes (42% versus 50%, respectively), and no significant difference in sensitivity for pelvic nodes (79% versus 83%, respectively) [23]. Likewise, CT had only modestly lower AUC (0.83) compared with PET/CT (0.90) for detection of nodal metastases from cervical cancer in a recent meta-analysis [24].


Staging and Follow up of Primary Vaginal Cancer. For distant metastases from cervical cancer, CT is inferior in the detection of osseous metastases (sensitivity 66%) compared with FDG-PET/CT (sensitivity 96%) [25]. These findings, if applied to vaginal cancer, suggest that CT is a reasonable staging tool for known or suspected tumor recurrence in the abdomen and pelvis, although it is likely inferior to MRI for evaluating local tumor extent, modestly inferior to FDG-PET/CT for nodal metastases, and inferior to FDG-PET/CT for osseous metastases. The use of IV contrast is strongly encouraged when possible, because the improved tissue contrast likely benefits primary tumor evaluation, delineation of lymph nodes from adjacent vessels, and detection of hepatic metastases. No studies have specifically assessed the performance of CT of the abdomen and pelvis without IV contrast for evaluation of known or suspected vaginal cancer recurrence. FDG-PET/CT Skull Base to Mid-Thigh No study has evaluated FDG-PET/CT in a cohort limited to patients with recurrent vaginal cancer. Data on the utility of FDG-PET/CT in this setting is limited to mixed cohorts of patients with various gynecologic malignancies, including vaginal cancer, with cervical squamous cell carcinoma generally comprising the majority of patients. One such cohort of 27 patients with recurrent gynecologic malignancies prior to pelvic exenteration was studied prospectively to compare FDG-PET and CT. FDG-PET was 100% sensitive and 73% specific for identifying extrapelvic metastases, most notably outperforming CT in the detection of pelvic and para-aortic nodal metastases [29]. A retrospective study of 85 patients with recurrent gynecologic malignancies reached similar conclusions, identifying findings suspicious for extraregional recurrence in 28% (24 of 85) of patients by PET versus 9% (8 of 85) of patients by conventional imaging (CT and pelvic MRI), with nodal metastases accounting for many of the discrepancies [30].


Staging and Follow up of Primary Vaginal Cancer. Concordant with these findings, the NCCN guidelines recommend whole-body FDG-PET/CT in patients with suspected recurrence of cervical cancer [27], although no such formal guidelines exist for vaginal cancer. Staging and Follow-up of Primary Vaginal Cancer Fluoroscopy Contrast Enema There is no relevant literature regarding the use of fluoroscopic contrast enema in the modern imaging workup of vaginal cancer, and its use has largely been replaced by cross-sectional imaging techniques. Although MRI readily depicts lymph nodes, it has constraints similar to CT with regard to the limited sensitivity and specificity of size and morphologic criteria. No study has evaluated the diagnostic performance of MRI for nodal staging isolated to a cohort of primary vaginal cancer patients with disease recurrence. However, data from mixed cohorts of patients with recurrence of cervical, vaginal, and other gynecologic cancers have suggested superior sensitivity of FDG-PET/CT for pelvic nodal metastases compared with pelvic MRI and CT [29,30]. The use of IV contrast may improve tissue characterization but is not considered essential, with variable inclusion in published protocols for evaluation of vaginal [28,31] and cervical cancer [7,32-34]. No study has specifically compared the incremental utility of gadolinium-enhanced sequences over T2-weighted sequences for pelvic MRI in this context. Regarding the use of vaginal gel in MRI of the pelvis, there is insufficient primary data in the literature to support its routine use. Although MRI readily depicts lymph nodes, it has constraints similar to CT with regard to the limited sensitivity and specificity of size and morphologic criteria. No study has evaluated the diagnostic performance of MRI for nodal staging isolated to a cohort of primary vaginal cancer patients with disease recurrence.


Staging and Follow up of Primary Vaginal Cancer. However, data from mixed cohorts of patients with recurrence of cervical, vaginal, and other gynecologic cancers have suggested superior sensitivity of FDG-PET/CT for pelvic nodal metastases compared with pelvic MRI and CT [29,30]. If MRI of the abdomen and pelvis is used in place of CT of the abdomen and pelvis, the addition of chest CT is encouraged to evaluate for pulmonary metastases. The use of IV contrast may improve tissue characterization and is particularly beneficial when MRI of the abdomen is included, because it improves detection of hepatic metastases. Radiography Intravenous Urography There is no relevant literature regarding the use of radiographic IV urography in the modern imaging workup of vaginal cancer, and its use has largely been replaced by cross-sectional imaging techniques. US Pelvis Transvaginal There is no relevant literature regarding the role of TVUS in the evaluation of known or suspected vaginal cancer recurrence nor is there any such literature for cervical cancer recurrence. Additionally, the potential applicability of TVUS for recurrent vaginal cancer would be limited to local recurrence, because TVUS has little to no utility for pelvic nodal evaluation [39]. Supporting Documents The evidence table, literature search, and appendix for this topic are available at https://acsearch. acr.org/list. The appendix includes the strength of evidence assessment and the final rating round tabulations for each recommendation. For additional information on the Appropriateness Criteria methodology and other supporting documents go to www. acr.org/ac. Appropriateness Category Names and Definitions Relative Radiation Level Information Potential adverse health effects associated with radiation exposure are an important factor to consider when selecting the appropriate imaging procedure.


Endometriosis

Endometriosis.  Introduction/Background Endometriosis is a common condition impacting approximately 10% of individuals assigned female at birth [1]. The disorder is caused by endometrial-like tissue located outside of the endometrial cavity, associated with inflammation and fibrosis, on or extending below the peritoneal surface [2]. Endometriosis that extends below the peritoneum is often referred to as deep endometriosis (DE). Endometriosis is usually multifocal and typically occurs in predictable locations in the pelvis. The diagnosis of endometriosis is challenging due to variable presenting symptoms and nonspecific physical examination findings [5]. Historically, the diagnosis of endometriosis was made by diagnostic laparoscopy with histologic inspection. Studies have shown that preoperative imaging is associated with decreased morbidity and mortality and reduces the need for repeat surgeries by reducing the number of incomplete surgeries. The literature now supports the use of imaging before surgery, because information gained from imaging studies helps inform patient decision making, is important for surgical planning, and impacts management [1,6,7]. Expert consensus groups advise using an MRI protocol tailored for detection of DE. Moderate bladder distention and vaginal contrast are recommended to help improve lesion conspicuity involving these structures [29]. There is aCleveland Clinic, Cleveland, Ohio. bPanel Chair, University of Michigan, Ann Arbor, Michigan. cClinica Family Health, Lafayette, Colorado; American Academy of Family Physicians. dUniversity of Kentucky, Lexington, Kentucky. eAlpert Medical School of Brown University, Providence, Rhode Island; Commission on Nuclear Medicine and Molecular Imaging. fHospital of the University of Pennsylvania, Philadelphia, Pennsylvania. gEmory University School of Medicine, Atlanta, Georgia; Committee on Emergency Radiology-GSER. hNew York University Langone Health, New York, New York. iVanderbilt University Medical Center, Nashville, Tennessee.


Endometriosis

Endometriosis. jUniversity of Michigan, Ann Arbor, Michigan. kMayo Clinic, Rochester, Minnesota. lSpecialty Chair, New York University Medical Center, New York, New York. The American College of Radiology seeks and encourages collaboration with other organizations on the development of the ACR Appropriateness Criteria through representation of such organizations on expert panels. Participation on the expert panel does not necessarily imply endorsement of the final document by individual contributors or their respective organization. Reprint requests to: publications@acr.org Endometriosis less agreement surrounding maneuvers to help improve detection of bowel lesions, including bowel preparation, rectal contrast, fasting, and administration of anti-peristaltic agents [30-34]. Though fluorine-18-2-fluoro-2-deoxy-D-glucose (FDG)-PET/CT has not been studied for the clinical variants described in this paper, a retrospective study showed that endometriosis can be detected on FDG-PET/CT [35]. The radiopharmaceutical fluoroestradiol, an estrogen analog PET agent currently approved for use in patients with metastatic breast cancer, has shown promise as an agent that can be used to detect endometriosis in early clinical trials [36]. OR Discussion of Procedures by Variant Variant 1: Adult. Clinically suspected pelvic endometriosis. Initial imaging. CT Pelvis With IV Contrast There is no relevant literature to support the use of pelvic CT with intravenous (IV) contrast as the initial imaging modality for clinically suspected endometriosis. CT Pelvis Without and With IV Contrast There is no relevant literature to support the use of pelvic CT without and with IV contrast as the initial imaging modality for clinically suspected endometriosis. CT Pelvis Without IV Contrast There is no relevant literature to support the use of pelvic CT without IV contrast as the initial imaging modality for clinically suspected endometriosis.


Endometriosis

Endometriosis. MRI Pelvis Without and With IV Contrast MRI pelvis is an excellent imaging modality for the preoperative diagnosis of endometriosis [37-39] and has been shown to correspond well with surgical staging systems and histopathologic findings [40-43]. Variability in the literature surrounding accuracy of MRI compared to other modalities for detection of endometriosis may be attributed to differences in imaging techniques used [40]. The performance of MRI for detection of endometriosis varies by lesion location. MRI is excellent for identification of DE but has shown poorer diagnostic accuracy for detection of superficial peritoneal disease [44-46]. Image acquisition is more automated for MRI than US [47]. The large field-of-view afforded by MRI can decrease the need for multiple additional imaging studies that are sometimes required to supplement US pelvis studies, which do not include the entire urinary or gastrointestinal tracts [48]. MRI Pelvis Without IV Contrast MRI pelvis without IV contrast is helpful for the diagnosis of DE as described in the preceding paragraph. Although much of the literature surrounding MRI of the pelvis for detection of DE describes using IV contrast agents, a study that specifically compared MRI without IV contrast to MRI with IV contrast found no benefit of IV contrast media [50]. Endometriosis US Pelvis Transabdominal Although it is possible that larger ovarian endometriomas could be detected by transabdominal pelvic US, many of the structures involved by superficial and DE are not well seen by transabdominal technique alone. US Pelvis Transabdominal and US Pelvis Transvaginal Transabdominal pelvic US imaging is described in some endometriosis protocols as an adjunct to TVUS imaging to evaluate the urinary tract or gastrointestinal tract [51]. Transabdominal US can serve as an important adjunct to TVUS studies because it widens the field-of-view beyond what is possible by TVUS imaging. Transabdominal US imaging is useful for detection of urinary tract endometriosis.


Endometriosis

Endometriosis. Urinary obstruction caused by involvement of the ureters or bladder can be silent and associated with loss of renal function [51]. Transabdominal US imaging can also help identify sites of bowel involvement beyond the pelvis, including the appendix, terminal ileum, cecum, and sigmoid [14]. DE TVUS supplemented by transabdominal US imaging was found to accurately predict intraoperative endometriosis staging at a multi-institutional study performed at centers of endometriosis excellence [52]. Variant 2: Adult. Clinically suspected pelvic endometriosis. Indeterminate or negative ultrasound. Next imaging study for characterization or treatment planning. CT Pelvis With IV Contrast There is no relevant literature to support the use of routine pelvic CT with IV contrast as a next imaging study for characterization or treatment planning of suspected pelvic endometriosis. CT Pelvis Without and With IV Contrast There is no relevant literature to support the use of routine pelvic CT without and with IV contrast as a next imaging study for characterization or treatment planning of suspected pelvic endometriosis. CT Pelvis Without IV Contrast There is no relevant literature to support the use of routine pelvic CT without IV contrast as a next imaging study for characterization or treatment planning of suspected pelvic endometriosis. MRI Pelvis Without and With IV Contrast A study that evaluated patients who underwent routine pelvic US and pelvic MRI with IV contrast and later went on to surgery for endometriosis found 51% of patients with a negative US went on to have disease identified on MRI. The same study showed that 78% of patients with endometriosis identified by US were found to have additional sites of disease by MRI [73]. MRI is known to correspond well with surgical staging systems and histopathologic findings [40-43]. Some pelvic MRI classification systems can predict surgical time, length of hospital stay, and postoperative complications [74].