Purpose Several organizations are developing clinical trials to evaluate adjuvant radiotherapy (RT) for bladder cancer patients at elevated risk of locoregional failure after radical cystectomy. Clinical target volumes (CTVs) and organs at risk (OARs) for this treatment have not been defined in detail. Our purpose was to develop multi-institutional consensus CTVs and OARs for male and female bladder cancer patients undergoing adjuvant RT in clinical trials. Methods and Materials We convened a multi-disciplinary group of bladder cancer specialists from fifteen centers and five countries. Six radiation oncologists and seven urologists participated in the development of the initial contours. The group proposed initial language for the CTVs and OARs, and each radiation oncologist contoured them on CT scans of a male and female cystectomy patient with input from ≥1 urologist. Based on the initial contouring, the group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another six radiation oncologists, and the cystectomy bed contouring language was again updated. To determine if the revised language produced consistent contours, CTVs and OARs were redrawn by six additional radiation oncologists. We evaluated their contours for level of agreement using the Landis-Koch interpretation of the κ-statistic. Results The group proposed that patients at elevated risk for local-regional failure with negative margins should be treated to the pelvic nodes alone (internal/external iliac, distal common iliac, obturator, and presacral) whereas patients with positive margins should be treated to the pelvic nodes and cystectomy bed. Proposed OARs included the rectum, bowel space, bone marrow, and urinary diversion. Consensus language describing the CTVs and OARs was developed and externally validated. The revised instructions were found to produce consistent contours. Conclusions Consensus descriptions of CTVs and OARs were successfully developed and can be employed in clinical trials of adjuvant RT for bladder cancer.

Context Radical cystectomy continues to be associated with a significant risk of morbidity and all-cause mortality (ACM). Practice pattern data demonstrating underuse of surgery for patients with muscle-invasive and high-risk non–muscle invasive bladder cancer (BC) have been linked to the advanced age and higher comorbidity status of such patients, which suggests that rates of ACM as well as cancer-specific mortality should be incorporated into patient counseling and guideline recommendations. Objective To review the literature on risk assessment tools for preoperative comorbidity in BC that may aid in treatment decision-making. Evidence acquisition A systematic search was conducted using Ovid and Medline according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2017 reporting on comorbidity risk assessment (CRA) tools for BC. Prospective and retrospective studies were included. Evidence synthesis There are no published randomized control trials comparing CRA tools for BC. Patients undergoing radical cystectomy with combined high-risk comorbidity and performance scores may face up to a sevenfold greater risk of other-cause mortality compared to those with low scores. The Charlson Comorbidity Index is one of the most widely studied indices for 90-d perioperative mortality and overall and cancer-specific survival, with an area under the receiver operating characteristic curve of up to 0.810. Prospective studies of CRA tools for BC have consistently shown that patients with higher comorbidity have worse outcomes. While not specific for BC, comorbidity indices provide useful assessment of competing risks. Competing-risks assessment tools are lacking, with limited studies assessing the impact of these tools on treatment decision-making by patients and providers. We provide the impetus for incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients. Conclusions CRA tools should be incorporated into preoperative treatment counseling and the assessment of postoperative outcomes. While retrospective evidence supports the use of CRA tools for BC, further comparative studies evaluating the effectiveness of these tools and identifying the patients most likely to benefit from a treatment according to competing-risks assessment are needed. Patient summary In this review we explored the clinical evidence for comorbidity risk assessment tools in bladder cancer. We found evidence to support incorporation of comorbidity risks into practice guidelines when discussing treatment options with patients.

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Introduction: We sought to determine predictors for early and late biochemical recurrence following radical prostatectomy among localized prostate cancer patients. Methods: The study included localized prostate cancer patients treated with radical prostatectomy (RP) at the University of Southern California from 1988 to 2008. Competing risks regression models were used to determine risk factors associated with earlier or late biochemical recurrence, defined using the median time to biochemical recurrence in this population (2.9 years after radical prostatectomy). Results:The cohort for this study included 2262 localized prostate cancer (pT2-3N0M0) patients who did not receive neoadjuvant or adjuvant therapies. Of these patients, 188 experienced biochemical recurrence and a subset continued to clinical recurrence, either within (n=19, 10%) or following (n=13, 7%) 2.9 years after RP. Multivariable stepwise competing risks analysis showed Gleason score ≥7, positive surgical margin status, and ≥pT3a stage to be associated with biochemical recurrence within 2.9 years following surgery. Predictors of biochemical recurrence after 2.9 years were Gleason score 7 (4+3), preoperative prostate-specific antigen (PSA) level, and ≥pT3a stage. Conclusions: Higher stage was associated with biochemical recurrence at any time following radical prostatectomy. Particular attention may need to be made to patients with stage ≥pT3a, higher preoperative PSA, and Gleason 7 prostate cancer with primary high-grade patterns when considering longer followup after RP. IntroductionRadical prostatectomy (RP) remains a mainstay of treatment for localized prostate cancer (PCa). However, up to 30% of patients will experience biochemical recurrence (BCR) following RP, [1][2][3][4] of which 20-30% will progress to clinical metastasis or recurrence (CR). 4,5 Although guidelines are available for post-RP surveillance, there is no clear consensus on an optimal followup strategy. 6, 7 Optimal risk stratification is crucial to avoid patient anxiety while tailoring risk-adapted surveillance and potentially earlier adjuvant therapy in those who require it.Existing models and nomograms using preoperative or postoperative clinical and pathologic data provide risk estimates of recurrence. [8][9][10][11][12] Few studies have further examined the timing of BCR after surgery as a possible predictor of metastatic disease and PCa-related mortality 4,5,[13][14][15] or the association of potential risk factors with earlier or later BCR. 1,16,17 Approximately 27% of BCR patients have been reported to experience late BCR. 13 In this study, we sought to determine clinical and pathologic characteristics predictive of early BCR vs. late BCR in a large cohort of patients treated with RP for localized PCa. Methods Patient populationThe University of Southern California maintained an institutional review board-approved database that included prospectively collected clinical data for 4063 males who underwent open radical retropubic prostatectomy with bilateral pelvic...

Objectives Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated. Methods Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low‐grade on URS biopsy) versus same grade (high‐grade on URS biopsy) for high‐grade UTUC tumors on radical nephroureterectomy (RNU) specimens. Results This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy‐based low‐ and high‐grade tumors, respectively. Median follow‐up was 27.3 months. Patients with high‐grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high‐grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10–2.75; p = 0.018), cancer‐specific (HR 1.94; 95% CI, 1.07–3.52; p = 0.03), and recurrence‐free survival (HR 1.80; 95% CI, 1.13–2.87; p = 0.013). In subgroup analyses of patients with pT2‐T4 and/or positive LN, its significant association retained. Furthermore, high‐grade biopsy in clinically non‐muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low‐grade biopsy. Conclusions High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low‐grade UTUC that becomes upgraded to high‐grade might carry a better prognosis than high‐grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high‐grade on RNU.