Biological and prognostic implications of biopsy upgrading for high-grade upper tract urothelial carcinoma at nephroureterectomy.

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.

Systematic Review of Comorbidity and Competing-risks Assessments for Bladder Cancer Patients.

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.

Development and Validation of Consensus Contouring Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy.

PURPOSE: To develop multi-institutional consensus clinical target volumes (CTVs) and organs at risk (OARs) for male and female bladder cancer patients undergoing adjuvant radiation therapy (RT) in clinical trials. METHODS AND MATERIALS: We convened a multidisciplinary group of bladder cancer specialists from 15 centers and 5 countries. Six radiation oncologists and 7 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 computed tomography scans of a male and female cystectomy patient with input from ≥1 urologist. On the basis of the initial contouring, the group updated its CTV and OAR descriptions. The cystectomy bed, the area of greatest controversy, was contoured by another 6 radiation oncologists, and the cystectomy bed contouring language was again updated. To determine whether the revised language produced consistent contours, CTVs and OARs were redrawn by 6 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 used in clinical trials of adjuvant radiation therapy for bladder cancer.

Collaborating to Move Research Forward: Proceedings of the 10th Annual Bladder Cancer Think Tank.

The 10th Annual Bladder Cancer Think Tank was hosted by the Bladder Cancer Advocacy Network and brought together a multidisciplinary group of clinicians, researchers, representatives and Industry to advance bladder cancer research efforts. Think Tank expert panels, group discussions, and networking opportunities helped generate ideas and strengthen collaborations between researchers and physicians across disciplines and between institutions. Interactive panel discussions addressed a variety of timely issues: 1) data sharing, privacy and social media; 2) improving patient navigation through therapy; 3) promising developments in immunotherapy; 4) and moving bladder cancer research from bench to bedside. Lastly, early career researchers presented their bladder cancer studies and had opportunities to network with leading experts.

Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA-era.

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.

Lessons learned from the International Renal Cell Carcinoma-Venous Thrombus Consortium (IRCC-VTC).

Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.

Super extended versus extended pelvic lymph node dissection in patients undergoing radical cystectomy for bladder cancer: a comparative study.

PURPOSE: There is evidence from retrospective studies that radical cystectomy with extended pelvic lymph node dissection provides better staging and outcomes than limited lymph node dissection. However, the optimal limits of extended lymph node dissection remain unclear. We compared oncological outcomes at 2 cystectomy centers where 2 different extended lymph node dissection templates are practiced to determine whether removing lymphatic tissue up to the inferior mesenteric artery confers an additional survival advantage. MATERIALS AND METHODS: Patients undergoing radical cystectomy and extended lymph node dissection with curative intent from 1985 to 2005 were included in analysis if they met certain criteria, including clinically organ confined urothelial bladder carcinoma (cN0M0), pathological stage pT2-pT3, negative surgical margins and no neoadjuvant therapy. Survival and recurrence data were analyzed. RESULTS: Demographic data and pathological subgroup distribution (pT2 and pT3) were similar in the 554 University of Southern California and 405 University of Bern patients. University of Southern California patients had higher median number of lymph nodes removed than University of Bern patients (38 vs 22, p <0.0001) and a higher incidence of lymph node metastasis (35% vs 28%, p = 0.02). However, the University of Southern California and University of Bern groups had similar 5-year recurrence-free survival for pT2pN0-2 (57% vs 67%) and pT3pN0-2 (32% vs 34%) disease (p = 0.55 and 0.44, respectively). The overall recurrence rate was equal at the 2 institutions (38%). CONCLUSIONS: Meticulous extended lymph node dissection up to the mid-upper third of the common iliac vessels appears to provide survival and recurrence outcomes similar to those of a super extended template up to the inferior mesenteric artery. Complete skeletonization in the extended lymph node dissection template is more important than nodal yield. This does not exclude the possibility that certain patient subgroups with suspicious nodes or after neoadjuvant chemotherapy may benefit from more extensive lymph node dissection.