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BACKGROUND: In oligoprogressive (OP) cancer there are a limited numbers of metastatic areas progressing on a background of stable or responding widespread cancer. While the standard-of-care for OP is changing systemic therapy (ST), stereotactic body radiotherapy (SBRT) is being explored as an alternative local therapy targeting the sites of progression. MATERIALS/METHODS: XXX (NCTXXX) was a single-centre phase-2 study of patients with metastatic genitourinary (GU), breast and gastrointestinal (GI) cancers, receiving ST for >3 months, with radiographic OP disease in <5 sites. Patients received SBRT to all OP disease in 1-5 fractions, and were maintained on ST. The primary endpoint was the cumulative incidence of change in ST estimated using Aalen-Johansen method. Secondary endpoints included progression-free survival (PFS) and overall survival (OS) estimated using Kaplan-Meier method, toxicity, and health-related quality-of-life (HRQOL). Comparisons between diagnosis groups were done using log-rank test. A two-sided p-value of <0.05 was considered as statistical significance. RESULTS: Seventy patients were analyzed, with median age 69 years; 32 patients (46%) were female; median number of lines of prior ST was 3. Primary sites were GU (n=32; 46%), breast (n=23; 33%) and GI (n=15; 21%). Median follow-up was 12.3 months (IQR 8.2-21.6). At 1-year, change in ST occurred in 47% (95% CI 36-61%) (GU 45%, breast 41%, GI 60%, p=0.23). PFS at 1-year was 32% (95% CI 23-45%), and median PFS was 4.7 months (95% CI 3.8-8.1) (GU 4.8, breast 6.5, GI 3.2), which significantly differed by disease type (p=0.006). OS was 75% at 1-year (95% CI 65-87%), which significantly differed between cancer type (GU 86%, breast 96%, GI 22%, p<0.001). Cumulative incidence of late grade >2 toxicity was 1.2%, with 1 patient experiencing late grade 3 toxicity, and no grade 4-5 acute or late toxicities. HRQOL declined from mean (standard deviation) of 66.9 (20.2) at baseline to 60.5 (22.2) at 6 months, which did not meet the threshold for a minimal clinically important difference. CONCLUSIONS: SBRT for OP metastases delayed change in ST in approximately half of patients, warranting investigation in randomized trials.

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BACKGROUND: Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies. METHODS: We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes. RESULTS: Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032). CONCLUSION: This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development.

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Papillary renal cell carcinoma (pRCC) is a rare kidney cancer with limited treatment options and poor outcomes when metastatic. We present a case of a 42-year-old male with metastatic pRCC harboring a somatic ataxia-telangiectasia mutated (ATM) mutation who was treated at our institution. After progression of disease (POD) on ipilimumab/nivolumab, followed by POD on cabozantinib, the patient was treated with radiation therapy to metastatic cervical lymphadenopathy to 60 Gy in 15 fractions as well as retroperitoneal lymphadenopathy to 36 Gy in 9 fractions, which was curtailed due to intolerance. This was followed by sequential systemic therapy with a poly (ADP-ribose) polymerase (PARP) inhibitor and pembrolizumab, which was also discontinued due to adverse effects. Despite not receiving any treatment for 10 months, his disease remains stable. We believe that the prolonged progression-free survival of this patient with ATM-mutation metastatic pRCC is likely due to the enhanced sensitivity of the tumor to radiation therapy due to ATM loss.

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BACKGROUND: Cutaneous melanoma (CM) is a significant health concern because of its high metastatic potential. Gene Expression Profile (GEP) testing, particularly the 31-GEP test (DecisionDx-Melanoma), has been increasingly used for risk stratification in CM patients. This study aimed to evaluate the clinical utility and performance of the 31-GEP test in a real-world setting. METHODS: Patients with CM who underwent 31-GEP testing from August 2014 to August 2022 at our institution were identified through searches of electronic health records. The study analyzed the influence of 31-GEP testing on clinical decision-making related to sentinel lymph node biopsy (SLNB), medical oncology referral, and postdiagnosis surveillance. Kaplan-Meier curves and Cox proportional hazard models were used to elucidate the test's performance, focusing on relapse-free survival (RFS) and melanoma-specific survival (MSS). RESULTS: The study included 65 CM patients. Dermatologists ordered more than 80% of 31-GEP tests. In 81.5% of cases, 31-GEP results did not alter standard clinical management. SLNB decisions were unaffected in 92% of patients with pre-SLNB 31-GEP results. Among patients with stage I-IIA melanoma, 25% of those with high-risk 31-GEP results were referred to medical oncology. Contrary to expectations, the rate of nodal metastasis was higher in low-risk than in high-risk 31-GEP cases. Survival analysis showed overlapping RFS and MSS curves between different 31-GEP classes, suggesting limited prognostic value. CONCLUSIONS: The 31-GEP test has a limited impact on clinical management decisions and shows limited prognostic value.

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Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a challenging disease, requiring personalized management by a multidisciplinary team. The aim of this retrospective multicentric study was to characterize real-world healthcare resource use and patient care for R/M HNSCC in Portugal during the first year after diagnosis. A total of 377 patients ineligible for curative treatment were included, mostly male (92.8%), aged 50-69 years (74.5%), with heavy alcohol (72.7%) or smoking habits (89.3%). Oropharynx (33.2%) and oral cavity (28.7%) were primary tumor locations, with lung metastases being the most common (61.4%). Eligible patients for systemic treatment with palliative intent (80.6%) received up to four treatment lines, with varied regimens. Platinum-based combination chemotherapy dominated first-line treatment (>70%), while single-agent chemotherapy and anti-PD1 immunotherapy were prevalent in later lines. Treatment approaches were uniform across disease stages and primary tumor locations but varied geographically. Treated patients received more multidisciplinary support than those who were ineligible. This study provides the first Portuguese real-world description of R/M HNSCC patient characteristics, treatment patterns, and supportive care during the year after diagnosis, highlighting population heterogeneity and aiming to improve patient management.

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BACKGROUND: In Indonesia incidence of colorectal cancer (CRC) remains high. Information about early symptoms that can offer clinicians insights for timely diagnosis, prompt referral and quick treatment decisions is very limited. This study aims to examine the pattern of CRC early symptoms and its association with tumor laterality, age at onset, metastatic status, and symptom-to-treatment initiation (STI) duration and delay. METHOD: This cross-sectional study recruits 258 patients diagnosed with CRC between November 2022 and October 2023 from two distinct study databases. Patient baseline characteristics were also obtained from medical records and through interviews at baseline. Symptom-to-treatment initiation (STI) duration was defined as the number of days between the date of the symptom's onset and the date of the first treatment's initiation. Relative risk estimation for metastatic disease and the STI delay, based on tumor laterality and the age at onset group, were estimated using a log-binomial regression for each early symptom. RESULT: Experiencing abdominal mass as an early symptom is significantly associated with metastatic disease, specifically in right-sided CRC cases (relative risk/RR=2.08, 95% confidence interval/CI 1.29-3.37, p=0.003). In all study subjects, the median STI duration was 182 days (2-5,082 days), with more than half of the subjects experiencing an STI delay of >180 days. Experiencing rectal mass as an early symptom is significantly associated with a higher risk of STI delay >180 days in early onset CRC (RR=1.97, 95% CI 1.27-3.06, p=0.003) and left sided-CRC cases (RR=1.54, 95% CI 1.13-2.08, p=0.005). The non-specific early symptom of weight loss is associated with a higher risk of STI delay >180 days in right-sided CRC cases (RR=1.73, 95% CI 1.06-2.84, p=0.029). CONCLUSION: The findings underlined the importance of maintaining a high clinical suspicion, particularly in patients with rectal masses and unexplained weight loss, as they might experience STI delay.

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The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies.

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Cervical cancer most commonly spreads hematogenously to the lungs, liver, and bone. However, it rarely metastasizes to the foot. There is only one other case of cervical cancer with metastasis to the foot. In addition, the initial imaging of metastatic disease has difficulty in differentiating from infectious or other inflammatory processes, particularly in a clinical setting highly suspicious of infectious sources. Here, we present a rare case of cervical cancer metastasizing to the calcaneus masquerading as osteomyelitis, highlighting the importance of diagnostic imaging in conjunction with histological confirmation.

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Vertebral body enhancement is occasionally seen on postcontrast CT imaging in the absence of osseous pathology. This enhancement can mimic sclerotic osseous metastatic disease, leading to a diagnostic dilemma for radiologists and increasing the chance of misinterpretation. Existing literature has focused on the association between this enhancement and concomitant central venous system obstruction. We report a 61-year-old woman with a history of nasopharyngeal carcinoma presenting with an epidural abscess who exhibited vertebral body enhancement resembling sclerotic metastatic disease without imaging evidence of central venous obstruction or vertebral osseous metastatic disease. Awareness of this unique presentation may prevent the incorrect diagnostic errors and their associated negative effects on patients.

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OBJECTIVE: To test the association between number as well as locations of organ-specific metastatic sites and overall survival (OS) in systhemic-therapy exposed metastatic urothelial carcinoma of urinary bladder (mUCUB) patients. METHODS: Within Surveillance, Epidemiology and End Results database (2010-2020), all systhemic therapy-exposed mUCUB patients were identified. Kaplan-Meier and multivariable Cox regression (CRM) models first addressed OS in patients according to number of metastatic organ-locations: solitary versus 2 versus 3 or more. Subsequently, separate analyses stratified according to location type were completed in patients with solitary metastatic organ-location as well as in patients with 2 metastatic organ-locations. RESULTS: Of 1,310 mUCUB, 1,069 (82%) harbored solitary metastatic organ-location versus 193 (15%) harbored 2 separate metastatic organ-locations versus 48 (3%) harbored 3 or more metastatic organ-locations. Median OS decreased with increasing number of metastatic organ-locations (solitary vs. 2 vs. 3 or more, P < .0001). In multivariable CRM, relative to solitary metastatic organ-location, 2 (HR: 1.57, 95 Confidence interval [CI], 1.33-1.85) as well as 3 or more (HR: 1.69, 95% CI, 1.23-2.31) metastatic organ-locations independently predicted higher overall mortality (OM) (P = .001). In patients with solitary metastatic organ-location, brain metastases independently predicted higher OM (HR 1.67; 95% CI, 1.05-2.67; P = .03) than other locations. In patients with 2 metastatic organ-locations, no differences in OM were recorded according to organ type location. CONCLUSION: In systemic therapy exposed mUCUB, number of metastatic organ-locations (solitary vs. 2 vs. 3 or more), independently predicted increasingly worse prognosis. In patients with solitary metastatic organ-location, brain purported worse prognosis than others.

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BACKGROUND: Pediatric gastroenteropancreatic neuroendocrine tumors are exceedingly rare, resulting in most pediatric treatment recommendations being based on data derived from adults. Trametinib is a kinase inhibitor that targets MEK1/2 and has been employed in the treatment of cancers harboring mutations in the Ras pathway. METHODS: We utilized an established human pediatric gastroenteropancreatic neuroendocrine-like tumor patient-derived xenograft (PDX) with a known NRAS mutation to study the effects of MEK inhibition. We evaluated the effects of trametinib on proliferation, motility, and tumor growth in vivo. We created an intraperitoneal metastatic model of this PDX, characterized both the phenotype and the genotype of the metastatic PDX and again, investigated the effects of MEK inhibition. RESULTS: We found target engagement with decreased ERK1/2 phosphorylation with trametinib treatment. Trametinib led to decreased in vitro cell growth and motility, and decreased tumor growth and increased animal survival in a murine flank tumor model. Finally, we demonstrated that trametinib was able to significantly decrease gastroenteropancreatic neuroendocrine intraperitoneal tumor metastasis. CONCLUSIONS: The results of these studies support the further investigation of MEK inhibition in pediatric NRAS mutated solid tumors.

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Background and objective: Visceral metastatic disease in prostate cancer patients conveys a poor prognosis. Using advanced imaging techniques, studies have demonstrated increasing detection rates of visceral metastasis. Visceral metastases are now seen in up to 30-60% of prostate cancer patients. Survival patterns of site-specific visceral metastasis are described poorly in the literature. Here, we sought to investigate survival patterns in prostate cancer patients according to their first detected site of visceral metastasis. Methods: Retrospectively, we identified 203 prostate cancer patients with visceral metastases from the Mayo Clinic Advanced Prostate Cancer Registry. Patients were divided into three groups according to the first site of visceral metastases detected: lung, brain, or liver. Visceral metastases were detected primarily on either metabolic imaging (C-11 choline) or prostate-specific membrane antigen positron emission tomography computed tomography (CT) scan. Confirmation of visceral metastasis diagnosis was established with either biopsy when feasible or focused conventional imaging, including focused CT or magnetic resonance imaging. Overall survival and cancer-specific survival were estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression model was conducted to assess different variables that affect overall and cancer-specific survival. Key findings and limitations: Over a median (interquartile range) follow-up duration of 16.2 (3.9-49.8) mo, the overall and cancer-specific survival of the entire cohort suggests better survival patterns in patients with first-site lung metastases than in patients with first-site brain or liver metastases (p < 0.0001). In univariate and multivariate analyses of factors impacting patients' overall and cancer-specific survival, a high prostate-specific antigen level at diagnosis of visceral metastasis, concomitant bone and lymph node disease, and more than four visceral metastases were associated with poor overall and cancer-specific survival (p < 0.05). On the contrary, first-site lung metastasis was associated with improved overall and cancer-specific survival, compared with first-site liver and brain metastases (p < 0.001). Conclusions and clinical implications: These data suggest that prostate cancer patients with visceral metastatic disease have varying survival patterns according to first-site detected visceral metastasis. In our cohort, patients with first-site lung metastasis demonstrated better survival outcomes than patients with first-site brain or liver metastasis. Patient summary: Our study explored the survival outcomes among patients with visceral metastatic prostate cancer employing cutting-edge imaging methods. Prostate cancer patients with metastases to different organs have different survival rates. Patients with cancer spreading to the lungs first showed better survival than those with cancer spreading to the brain or liver first.

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Introduction: Basal cell carcinoma (BCC) is treated with local surgery or noninvasive treatment modalities. If a BCC remains untreated, it can develop into a locally advanced BCC or a metastatic BCC. Case Presentation: Here we report in detail the management of three complex advanced BCC (aBCC) after treatment failure with vismodegib. On all tumors, next generation DNA sequencing in the Center for Personalized Cancer Treatment-02 (CPCT-02) study was performed; subsequently, patients were included in the Drug Rediscovery Protocol (DRUP) trial, in which treatment was started with commercially available targeted anticancer drugs based on the molecular tumor profile. All patients showed partial response or stable disease following treatment with second line PD-1 inhibitors with an average duration of response of 12.3 months. Discussion/Conclusion: Immunotherapy can be a treatment option for aBCC resistant to hedgehog pathway inhibitor treatment. However, despite the high tumor mutational burden of aBCCs, immunotherapy does not always lead to a long response. Rechallenge or combining treatment of hedgehog inhibitors and PD-1 inhibitors by parallel or alternating cycles may be a strategy to lengthen the treatment response.

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Objective.Deep learning models that aid in medical image assessment tasks must be both accurate and reliable to be deployed within clinical settings. While deep learning models have been shown to be highly accurate across a variety of tasks, measures that indicate the reliability of these models are less established. Increasingly, uncertainty quantification (UQ) methods are being introduced to inform users on the reliability of model outputs. However, most existing methods cannot be augmented to previously validated models because they are not post hoc, and they change a model's output. In this work, we overcome these limitations by introducing a novel post hoc UQ method, termedLocal Gradients UQ, and demonstrate its utility for deep learning-based metastatic disease delineation.Approach.This method leverages a trained model's localized gradient space to assess sensitivities to trained model parameters. We compared the Local Gradients UQ method to non-gradient measures defined using model probability outputs. The performance of each uncertainty measure was assessed in four clinically relevant experiments: (1) response to artificially degraded image quality, (2) comparison between matched high- and low-quality clinical images, (3) false positive (FP) filtering, and (4) correspondence with physician-rated disease likelihood.Main results.(1) Response to artificially degraded image quality was enhanced by the Local Gradients UQ method, where the median percent difference between matching lesions in non-degraded and most degraded images was consistently higher for the Local Gradients uncertainty measure than the non-gradient uncertainty measures (e.g. 62.35% vs. 2.16% for additive Gaussian noise). (2) The Local Gradients UQ measure responded better to high- and low-quality clinical images (p< 0.05 vsp> 0.1 for both non-gradient uncertainty measures). (3) FP filtering performance was enhanced by the Local Gradients UQ method when compared to the non-gradient methods, increasing the area under the receiver operating characteristic curve (ROC AUC) by 20.1% and decreasing the false positive rate by 26%. (4) The Local Gradients UQ method also showed more favorable correspondence with physician-rated likelihood for malignant lesions by increasing ROC AUC for correspondence with physician-rated disease likelihood by 16.2%.Significance. In summary, this work introduces and validates a novel gradient-based UQ method for deep learning-based medical image assessments to enhance user trust when using deployed clinical models.

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BACKGROUND OBJECTIVES: The aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value. METHODS: We examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016-2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression. RESULTS: Median overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001). CONCLUSION: While synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies.

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INTRODUCTION: Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in the treatment of recurrent and/or metastatic (RM) head and neck squamous cell carcinoma (HNSCC) Keynote 048 highlighted the relevance of PD-L1 Combined Positive Score (CPS) as a predictive biomarker for ICIs treatment, but challenges persist regarding ideal assessment and concordance between primary and relapsing tumor has not been determined. MATERIAL AND METHODS: This is a retrospective multicentric study that included HNSCC patients with locoregional and/or metastatic relapses after curative treatment. Histological samples of primary tumors and corresponding relapses were collected. The primary objective was to evaluate PD-L1 CPS concordance between primary and recurrent tumors, with secondary objective of exploring the impact of clinical-pathological variables. RESULTS: Out of 86 evaluated patients, 30 cases were excluded due to insufficient histological material, with a final enrollment of 56 patients. Concordance analysis revealed a 66.1% agreement in PD-L1 CPS between primary and recurrent tumors. Only 3.6% of cases exhibited a change from negative to positive PD-L1 CPS status, and 7.2% showed the reverse. Factors analyzed, including primary tumor site, treatment modality, and recurrence type, did not significantly influence PD-L1 CPS concordance level. CONCLUSION: While significant changes in PD-L1 CPS expression are rare, the study underscores the importance of confirmatory biopsies on relapse. However, reliance on archival tumor tissue for initial PDL1 assessment may be considered in cases where obtaining additional biopsies poses risks to patients or urgent therapeutic decisions are required.

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AIMSWERNER SYNDROME IS A RARE PREMATURE AGEING AUTOSOMAL RECESSIVE DISORDER CAUSED BY PATHOGENIC VARIANTS IN THE WRN GENE. PEOPLE WITH WERNER SYNDROME MAY DEVELOP DIABETES MELLITUS. CHRONIC FOOT ULCERATION IS SEEN, WITH SOME CHARACTERISTICS OVERLAPPING WITH DIABETIC FOOT DISEASE. HOWEVER, THE CLINICAL COURSE OF THE ULCERATION IS ATYPICAL OF DIABETIC FOOT DISEASE. WE PRESENT FOUR SIBLINGS FROM AN IRISH TRAVELLER FAMILY WITH WERNER SYNDROME TO HIGHLIGHT THE COMPLEXITY OF THIS CONDITION. THE IRISH TRAVELLER POPULATION ARE AN INDIGENOUS, ENDOGAMOUS POPULATION IN WHICH CONSANGUINITY IS COMMON. AS A RESULT, RARE AUTOSOMAL RECESSIVE DISORDERS ARE PREVALENT AMONG THIS POPULATION: . METHODS: We describe our experience managing the complex foot disease seen in all four siblings. Foot complications present in the siblings include painful peripheral neuropathy, chronic foor ulceration, underlying osteomyelitis and acral melanoma. RESULTS: The cases are described individually, with a particular focus on the complex foot disease associated with the condition. CONCLUSIONS: Although the siblings attend a diabetic foot clinic, we suggest that the combination of clinical features seen in these cases is unique to Werner syndrome and warrants the title 'Werner Syndrome' (rather than 'Diabetic') foot.

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As the proportion of women diagnosed with invasive breast cancer increases, the role of imaging for staging and surveillance purposes should be determined based on evidence-based guidelines. It is important to understand the indications for extent of disease evaluation and staging, as unnecessary imaging can delay care and even result in adverse outcomes. In asymptomatic patients that received treatment for curative intent, there is no role for imaging to screen for distant recurrence. Routine surveillance with an annual 2-D mammogram and/or tomosynthesis is recommended to detect an in-breast recurrence or a new primary breast cancer in women with a history of breast cancer, and MRI is increasingly used as an additional screening tool in this population, especially in women with dense breasts. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

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BACKGROUND: Various risk classification systems (RCSs) are used globally to stratify newly diagnosed patients with prostate cancer (PCa) into prognostic groups. OBJECTIVE: To compare the predictive value of different prognostic subgroups (low-, intermediate-, and high-risk disease) within the RCSs for detecting metastatic disease on prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) for primary staging, and to assess whether further subdivision of subgroups would be beneficial. DESIGN, SETTING, AND PARTICIPANTS: Patients with newly diagnosed PCa, in whom PSMA-PET/CT was performed between 2017 and 2022, were studied retrospectively. Patients were stratified into risk groups based on four RCSs: European Association of Urology, National Comprehensive Cancer Network (NCCN), Cambridge Prognostic Group (CPG), and Cancer of the Prostate Risk Assessment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The prevalence of metastatic disease on PSMA-PET/CT was compared among the subgroups within the four RCSs. RESULTS AND LIMITATIONS: In total, 2630 men with newly diagnosed PCa were studied. Any metastatic disease was observed in 35% (931/2630) of patients. Among patients classified as having intermediate- and high-risk disease, the prevalence of metastases ranged from approximately 12% to 46%. Two RCSs further subdivided these groups. According to the NCCN, metastatic disease was observed in 5.8%, 13%, 22%, and 62% for favorable intermediate-, unfavorable intermediate-, high-, and very-high-risk PCa, respectively. Regarding the CPG, these values were 6.9%, 13%, 21%, and 60% for the corresponding risk groups. CONCLUSIONS: This study underlines the importance of nuanced risk stratification, recommending the further subdivision of intermediate- and high-risk disease given the notable variation in the prevalence of metastatic disease. PSMA-PET/CT for primary staging should be reserved for patients with unfavorable intermediate- or higher-risk disease. PATIENT SUMMARY: The use of various risk classification systems in patients with prostate cancer helps identify those at a higher risk of having metastatic disease on prostate-specific membrane antigen positron emission tomography/computed tomography for primary staging.