Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

Real-time estimation of nephron activity with a linear measurement system (RENAL-MS) predicts postoperative estimated glomerular filtration rate.

OBJECTIVE: To determine whether a simple point-of-care measurement system estimating renal parenchymal volume using tools ubiquitously available could be used to replace nuclear medicine renal scintigraphy (NMRS) in current clinical practice to predict estimated glomerular filtration rate (eGFR) after nephrectomy by estimating preoperative split renal function. PATIENTS AND METHODS: We performed a retrospective review of patients who underwent abdominal cross-sectional imaging (computed tomography/magnetic resonance imaging) and mercaptoacetyltriglycine (MAG3) NMRS prior to total nephrectomy at a single institution. We developed the real-time estimation of nephron activity with a linear measurement system (RENAL-MS) method of estimating postoperative renal function via the following technique: renal parenchymal volume of the removed kidney relative to the remaining kidney was estimated as the product of renal length and the average of six renal parenchymal thickness measurements. The utility of this value was compared to the utility of the split renal function measured by MAG3 for prediction of eGFR and new onset Stage 3 chronic kidney disease (CKD) at ≥90 days after nephrectomy using uni- and multivariate linear and logistic regression. RESULTS: A total of 57 patients met the study criteria. The median (interquartile range [IQR]) age was 69 (61-80) years. The median (IQR) pre- and postoperative eGFR was 74 (IQR 58-90) and 46 (35-62) mL/min/1.73 m2 , respectively. [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] Correlations between actual and predicted postoperative eGFR were similar whether the RENAL-MS or NMRS methods were used, with correlation using RENAL-MS being slightly numerically but not statistically superior (R = 0.82 and 0.76; P = 0.138). Receiver operating characteristic curve analysis using logistic regression estimates incorporating age, sex, and preoperative creatinine to predict postoperative Stage 3 CKD were similar between RENAL-MS and NMRS (area under the curve 0.93 vs. 0.97). [Correction added on 29 December 2023, after first online publication: The data numbers in the preceding sentence have been corrected.] CONCLUSION: A point-of-care tool to estimate renal parenchymal volume (RENAL-MS) performed equally as well as NMRS to predict postoperative eGFR and de novo Stage 3 CKD after nephrectomy in our population, suggesting NMRS may not be necessary in this setting.

Clinical Performance of Technetium-99m-Sestamibi SPECT/CT Imaging in Differentiating Oncocytic Tumors From Renal Cell Carcinoma in Routine Clinical Practice.

PURPOSE: Technetium-99m-sestamibi single-photon emission CT/x-ray CT is an emerging clinical tool to differentiate oncocytic tumors from renal cell carcinomas. We report data from a large institutional cohort of patients who underwent technetium-99m-sestamibi scans during evaluation of renal masses. MATERIALS AND METHODS: Patients who underwent technetium-99m-sestamibi single-photon emission CT/x-ray CT between February 2020 and December 2021 were included in the analysis. Scans were defined as "hot" for oncocytic tumor when technetium-99m-sestamibi uptake was qualitatively equivalent or higher between the mass of interest and normal renal parenchyma, suggesting oncocytoma, hybrid oncocytic/chromophobe tumor, or chromophobe renal cell carcinoma. Demographic, pathological, and management strategy data were compared between "hot" and "cold" scans. For individuals who underwent diagnostic biopsy or extirpative procedures, the concordance between radiological findings and pathology was indexed. RESULTS: A total of 71 patients (with 88 masses) underwent technetium-99m-sestamibi imaging with 60 (84.5%) patients having at least 1 "cold" mass on imaging and 11 (15.5%) patients exhibiting only "hot" masses. Pathology was available for 7 "hot" masses, with 1 biopsy specimen (14.3%) being discordant (clear cell renal cell carcinoma). Five patients with "cold" masses underwent biopsy. Out of 5 biopsied masses, 4 (80%) were discordant oncocytomas. Of the extirpated specimens, 35/40 (87.5%) harbored renal cell carcinoma and 5/40 (12.5%) yielded discordant oncocytomas. In sum, 20% of pathologically sampled masses that were "cold" on technetium-99m-sestamibi imaging still harbored oncocytoma/hybrid oncocytic/chromophobe tumor/chromophobe renal cell carcinoma. CONCLUSIONS: Further work is needed to define utility of technetium-99m-sestamibi in real-world clinical practice. Our data suggest this imaging strategy is not yet ready to replace biopsy.

Pathological and Clinical Outcomes in a Large Surveillance and Intervention Cohort of Radiographically Cystic Renal Masses.

PURPOSE: We evaluated oncologic risks in a large cohort of patients with radiographic cystic renal masses who underwent active surveillance or intervention. MATERIALS AND METHODS: A single-institutional database of 4,340 kidney lesions managed with either active surveillance or intervention between 2000-2020 was queried for radiographically cystic renal masses. Association of radiographic tumor characteristics and high-grade pathology was evaluated. RESULTS: We identified 387 radiographically confirmed cystic lesions in 367 patients. Of these, 247 were resected (n=240) or ablated (n=7; n=247, 203 immediate vs 44 delayed intervention). Pathologically, 23% (n=56) demonstrated high-grade pathology. Cystic features were explicitly described by pathology in only 18% (n=33) of all lesions and in 7% (n=4) of high-grade lesions. Of the intervention cohort, African American race, male gender, and Bosniak score were associated with high-grade pathology (P < .05). On active surveillance (n=184), Bosniak IV lesions demonstrated faster growth rates than IIF and III lesions (2.7 vs 0.6 and 0.5 mm/y, P ≤ .001); however, growth rates were not associated with high-grade pathology (P = .5). No difference in cancer-specific survival was identified when comparing intervention vs active surveillance at 5 years (99% vs 100%, P = .2). No difference in recurrence was observed between immediate intervention vs delayed intervention (P > .9). CONCLUSIONS: A disconnect between "cystic" designation on imaging and pathology exists for renal lesions. Over 80% of radiographic Bosniak cystic lesions are not described as "cystic" on pathology reports. More than 1 in 5 resected cystic renal lesions demonstrated high-grade disease. Despite this finding, judiciously managed active surveillance ± delayed intervention is a safe and effective management option for most radiographic cystic renal masses.

A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study.

BACKGROUND: Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients. OBJECTIVE: To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). DESIGN, SETTING, AND PARTICIPANTS: A multicenter phase 1 trial was conducted at community and academic sites. INTERVENTION: Patients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-treatment cystoscopy and urine cytology were performed at 3 and 6 -mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates. RESULTS AND LIMITATIONS: Twenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients. CONCLUSIONS: D combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches. PATIENT SUMMARY: Durvalumab combination therapy can be safely administered to non-muscle-invasive bladder cancer patients with the goal of increasing durable response rates.

Long-Term Results of a Phase 3 Randomized Prospective Trial of Erectile Tissue-Sparing Intensity-Modulated Radiation Therapy for Men With Clinically Localized Prostate Cancer.

PURPOSE: The objective of this study was to determine whether limiting the doses delivered to the penile bulb (PB) and corporal bodies with intensity modulated radiation therapy (IMRT) preserves erectile function compared with standard IMRT in men with prostate cancer. METHODS AND MATERIALS: A total of 117 patients with low- to intermediate-risk, clinical T1a-T2c prostate adenocarcinoma were enrolled in a single-institution, prospective, single-blind, phase 3 randomized trial. All received definitive IMRT to 74 to 80 Gy in 37 to 40 fractions and standard IMRT (s-IMRT) or erectile tissue-sparing IMRT (ETS-IMRT), which placed additional planning constraints that limited the D90 to the penile bulb and corporal bodies to ≤15 Gy and ≤7 Gy, respectively. Erectile potency was assessed with components of the International Index of Erectile Function and phosphodiesterase type 5 inhibitor (PDE5) medication records. RESULTS: Sixty-two patients received ETS-IMRT, and 54 received s-IMRT; 1 patient did not receive radiation therapy. Before treatment, all patients reported erectile potency. No patients received androgen deprivation therapy. In the intention-to-treat analysis, treatment arms did not differ in potency preservation at 24 months (37.1% ETS-IMRT vs 31.5% s-IMRT, P = .53). Of 85 evaluable patients with International Index of Erectile Function and PDE5 medication follow-up, erectile potency was seen in 47.9% of patients in the ETS-IMRT arm and 46.0% of patients in the s-IMRT arm (P = .86). PDE5 inhibitors were initiated in 41.7% of ETS-IMRT patients and 35.1% of s-IMRT patients (P = .54). Among all patients enrolled, there was no difference in freedom from biochemical failure between those treated with ETS-IMRT and s-IMRT (5-year 91.8% vs 90.7%, respectively, P = .77), with a median follow-up of 7.4 years. There were no differences in acute or late gastrointestinal or genitourinary toxicity. An unplanned per-protocol analysis demonstrated no differences in potency preservation or secondary endpoints between patients who exceeded erectile tissue-sparing constraints and those who met constraints, although power was limited by attrition and unplanned dosimetric crossover. CONCLUSIONS: ETS-IMRT that strictly limits dose to the penile bulb and corporal bodies is safe and feasible. Use of this planning technique did not show an effect on potency preservation outcomes at 2 years, though power to detect a difference was limited.

No difference in renal function outcomes for patients with oncocytoma managed with active surveillance vs. partial nephrectomy.

OBJECTIVES: To investigate the difference in renal function outcomes for patients with oncocytomas undergoing active surveillance (AS) vs. partial nephrectomy (PN). METHODS: We reviewed our institutional database for patients with biopsy/surgically confirmed oncocytoma from 2000-2020. The primary outcome was to assess for differences in renal function outcomes in patients undergoing AS vs. PN. We fit two generalized estimating equation (GEE) with an interaction term between follow up time and management strategy to predict 1) mean eGFR for patients managed with AS and PN and 2) the probability of progression to CKD stage III or greater. RESULTS: We identified 114 eligible patients, of which 32 were managed with AS. Median follow-up was 21 months vs. 44 months for PN vs. AS patients. AS patients tended to be older (median: 72 years vs. 65 years, P<0.001) and have lower baseline renal function (median: eGFR: 71 mL/min/1.73m2 vs. 82 mL/min/1.73m2, P<0.001) compared with PN patients. Renal mass size from baseline imaging was similar between patients undergoing PN vs. AS (2.8 cm vs. 2.9 cm, P=0.634). For patients undergoing PN vs. AS, there was not a significant difference in predicted longitudinal eGFR (-0.079, 95% CI -0.18-0.023, P=0.129) or predicted probability of progression to CKD stage III or greater (OR: 0.61, 95% CI: 0.16-2.33, P=0.47). CONCLUSIONS: In our institutional dataset, patients undergoing AS or PN with an oncocytoma had similar long-term renal function outcomes. Given similar renal function outcomes in patients undergoing AS and PN, surgery should remain reserved for select patients with oncocytomas.

NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022.

The NCCN Guidelines for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer and other urinary tract cancers (upper tract tumors, urothelial carcinoma of the prostate, primary carcinoma of the urethra). These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines regarding the treatment of non-muscle-invasive bladder cancer, including how to treat in the event of a bacillus Calmette-Guérin (BCG) shortage; new roles for immune checkpoint inhibitors in non-muscle invasive, muscle-invasive, and metastatic bladder cancer; and the addition of antibody-drug conjugates for metastatic bladder cancer.

Association of tumor size and surgical approach with oncological outcomes and overall survival in patients with adrenocortical carcinoma.

OBJECTIVES: To investigate the association of surgical approach with outcomes in patients with adrenocortical carcinomas smaller and larger than 6 cm in size. METHODS: We reviewed the national cancer database for patients undergoing minimally invasive adrenalectomy (MIA) and open adrenalectomy (OA) from 2010 to 2017. To adjust for differences between patients undergoing MIA and OA, we performed propensity score matching within each size strata of ≤6 cm, 6.1 to 10 cm, and 10.1 to 20 cm. We fit generalized estmiating equations with a logit link function to assess for the association of surgical approach with positive surgical margins and a Cox proportional hazards model to assess for the association of surgical approach with overall survival. RESULTS: We identified 364 patients that underwent MIA (182) and OA (182) in the matched cohort.  We noted 21% and 18% of patients undergoing MIA and OA had a positive surgical margin, respectively. We did not identify a significant association between surgical approach and positive surgical margins in the cohort as a whole or within each of strata. Furthermore, we did not appreciate a significant association between surgical approach and overall survival in the cohort as a whole or within each size strata. CONCLUSION: In the National Cancer Database, patients undergoing MIA had similar positive surgical margins and overall survival compared with OA for masses ≤6 cm, 6.1 to 10cm, and >10 cm in size. Patients undergoing MIA should be carefully selected with surgical oncologic integrity being the primary determinants of surgical approach.

Association of Surgical Approach With Treatment Burden, Oncological Effectiveness, and Perioperative Morbidity in Adrenocortical Carcinoma.

MICROABSTRACT: In the National Cancer Database (NCDB), patients treated with minimally invasive adrenalectomy (MIA) for adrenocortical carcinoma (ACC) had similar oncological outcomes and cumulative treatment burden with less morbidity compared with open adrenalectomy (OA). Although OA remains the standard of care for adrenal lesions concerninge for malignancy, MIA in appropriately selected patients may offer equivalent oncological outcomes. INTRODUCTION/BACKGROUND: We investigated the cumulative treatment burden, oncological effectiveness, and perioperative morbidity in patients undergoing MIA compared with (OA) for patients with ACC. PATIENTS AND METHODS: We reviewed the NCDB for patients undergoing surgical resection (MIA vs. OA) for ACC from 2010 to 2017. Inverse probability of treatment weighted logistic regression, negative binomial, and Cox proportional hazards models were fit to assess for an association of surgical approach with cumulative treatment burden (any adjuvant therapy, radiation therapy [RT], and systemic therapy), oncological effectiveness (positive surgical margins [PSM], lymph node yield [LNY], and overall survival [OS]), and perioperative morbidity (length of stay [LOS] and readmission) as appropriate. RESULTS: We identified 776 patients that underwent adrenalectomy for ACC, of which 307 underwent MIA. We noted patients with larger tumors (OR 0.82, 95% CI 0.78-0.86, P < .001) were less likely to have MIA prior to IPTW. We did not appreciate a significant association of MIA with cumulative treatment burden or the use of any adjuvant therapy (OR 0.85, 95% CI 0.60-1.21, P = .375), adjuvant RT (OR 0.94, 95% CI 0.59-1.50, P = .801), or adjuvant systemic therapy (OR 0.84, 95% CI 0.58-1.21, P = .352). Patients undergoing MIA had similar oncological effectiveness of surgery and OS when compared with patients which underwent OA. Patients that underwent MIA had a significantly shorter LOS (IRR: 0.74, 95% CI 0.62-0.88, P = .001) and lower odds of readmission (OR 0.46, 95% CI 0.23-0.91, P = .026). CONCLUSIONS: Although the standard of care for adrenal lesions suspicious for ACC remains OA, in appropriately selected patients, MIA may offer similar oncological effectiveness and cumulative treatment burden, with less morbidity, than OA.

The Role of Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: A Real-World Multi-Institutional Analysis.

PURPOSE: The role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) was challenged by the results of the CARMENA trial. Here we evaluate the role of CN in mRCC patients, including those receiving modern therapies. MATERIALS AND METHODS: We included patients with synchronous mRCC between 2011-2020 from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic therapy alone, CN followed by systemic therapy (up-front CN [uCN]) and systemic therapy followed by CN (deferred CN [dCN]). The primary outcome was median overall survival (mOS) in patients receiving systemic therapy alone vs uCN. Secondary outcome was overall survival in patients receiving uCN vs dCN. First-treatment, landmark and time-varying covariate analyses were conducted to overcome immortal time bias. Weighted Kaplan-Meier curves, log-rank tests and Cox proportional hazards regressions were used to assess the effect of therapy on survival. RESULTS: Of 1,910 patients with mRCC, 972 (57%) received systemic therapy, 605 (32%) received uCN, 142 (8%) dCN and 191 (10%) CN alone; 433 (23%) patients received immunotherapy-based therapy. The adjusted mOS was significantly improved in first-treatment, landmark and time-varying covariate analysis (mOS 26.6 vs 14.6 months, 36.3 vs 21.1 months and 26.1 vs 12.2 months, respectively) in patients undergoing CN. Among patients receiving CN and systemic therapy, the timing of systemic therapy relative to CN was not significantly related to overall survival (HR=1.0, 95% CI 0.76-1.32, p=0.99). CONCLUSIONS: Our findings support an oncologic role for CN in select mRCC patients. In patients receiving both CN and systemic therapy, the survival benefit compared to systemic alone was similar for up-front and deferred CN.

Safety of neoadjuvant chemotherapy in patients with muscle-invasive bladder cancer and malignant ureteric obstruction.

OBJECTIVES: To determine whether patients with carcinoma invading bladder muscle (MIBC) and ureteric obstruction can safely receive cisplatin-based neoadjuvant chemotherapy (C-NAC), and to determine whether such patients require relief of obstruction with a ureteric stent or percutaneous nephrostomy prior to beginning C-NAC. PATIENTS AND METHODS: We performed a single-institution retrospective analysis of MIBC patients receiving C-NAC and falling into three groups: no ureteric obstruction (NO); relieved ureteric obstruction (RO); and unrelieved ureteric obstruction (URO). To address whether patients with obstruction can safely receive C-NAC, we compared patients with NO to those with RO, with the primary outcome of premature chemotherapy discontinuation. To investigate whether patients with obstruction should have the obstruction relieved prior to NAC, we compared RO to URO patients using a primary composite outcome of grade ≥ 3 adverse events, premature chemotherapy discontinuation, dose reduction, or dose interruption. The primary outcomes were compared using multivariable logistic regression. Sensitivity analyses were performed for the RO vs URO comparison, in which patients with only mild degrees of obstruction were excluded from the URO group. RESULTS: A total of 193 patients with NO, 49 with RO, and 35 with URO were analysed. There were no statistically significant differences between those with NO and those with RO in chemotherapy discontinuation (15% vs 22%; P = 0.3) or any secondary outcome. There was no statistically significant difference between those with RO and URO in the primary composite outcome (51% vs 53%; P = 1) or any secondary outcome. CONCLUSION: Patients with ureteric obstruction can safely receive C-NAC. Relief of obstruction was not associated with increased safety of C-NAC delivery.

Oncologic Outcomes of cT1 and cT2 Micropapillary Variant Compared with cT1 and cT2 Conventional Urothelial Carcinoma Treated with Radical Cystectomy.

INTRODUCTION: Our objective was to estimate the difference in outcomes for patients with clinical T stage 1 (cT1) and 2 (cT2) micropapillary (MPBC) and urothelial carcinoma (UCBC) bladder cancer treated with radical cystectomy (RC). METHODS: We reviewed the National Cancer Database for patients with cT1/2N0M0 MPBC and UCBC treated with RC from 2004-2016. Patients were classified by cT stage and histology. Outcomes of interest included upstaging to advanced pathological stage (pT3/4), pathologically node positive disease (pN+), and overall survival (OS). The Kaplan-Meier method was used to estimate 5-year OS probability. Multivariable logistic regression models were fit to test for an association between cT stage and histology with outcomes. RESULTS: We identified 23,871 patients, of whom 384 had MPBC and 23,487 had UCBC. More patients with cT1 and cT2 MPBC had advanced pathological stage and pN+ (cT1: 31% and 34%; cT2: 44% and 60%, respectively) compared with cT1 and cT2 UCBC (cT1: 18% and 14%; cT2: 27% and 24%, respectively). Compared with cT2 UCBC, patients with cT1 MPBC had similar odds of advanced pathological stage (OR: 0.96, 95% CI: 0.63-1.45, p=0.837) and increased odds of pN+ (OR: 1.62, 95% CI: 1.03-2.56, p=0.038). Five-year OS estimates for cT1 MPBC and UCBC were similar (58% and 60%, respectively) while cT2 MPBC had worse OS than cT2 UCBC (33% and 45%, respectively). CONCLUSIONS: In a cohort of patients undergoing RC, cT1/2 MPBC had worse outcomes than cT1/2 UCBC. Patients and surgeons should consider aggressive therapies for patients with cT1 MPBC due to the risk of inferior outcomes associated with cT2 MPBC disease.

Renal mass biopsy: A strategy to reduce associated costs and morbidity when managing localized renal masses.

INTRODUCTION AND OBJECTIVES: Renal mass biopsy (RMB) has not been widely adopted in evaluating small renal mass due to concerns for safety, efficacy, and its perceived lack of consequence on management decisions. We assess the potential cost savings and morbidity avoidance of routine RMB on cT1 renal masses undergoing robotic-assisted partial nephrectomy (RAPN). METHODS: We identified n = 920 consecutive RAPN pT1 renal masses and n = 429 consecutive RMBs for cT1 renal masses over 12 years. Using a novel pathological-based risk classification system for cT1 renal masses, we evaluated the morbidity and costs of our RAPN and RMB cohorts. We then define four clinical scenarios where RMB could potentially delay and/or avoid intervention in our pT1 RAPN cohort and model potential complications prevented and cost savings utilizing common clinical scenarios. RESULTS: Using our risk stratification system in RAPN patients, final histology was classified as benign in n=174 (18.9%) cases, very low-risk (n = 62 [7%]), low-risk (n = 383 [42%]), and high-risk (n = 301 [33%]), respectively. We identified n = 116 (12.6%) Clavien graded peri-operative complications. In our RMB patients, 120 (27.9%), 17 (3.9%), 240 (55.9%), 52(12.1%) were benign, very low, low and high-risk tumors. The median total direct cost for RAPN was $6955/case compared to $1312/case for RMB. If we established a primary goal to avoid immediate extirpative surgery in benign renal tumors, in the elderly (>70 y) with very low-risk tumors and/or those with high renal functional risks (≥ CKD3b), or competing risks (ASA ≥ 3), RMB could have reduced direct costs by approximately 20% and avoided n = 39 Clavien graded complications, seven readmissions, three transfusions, and two returns to the OR. With the additional cost of performing RMB on those not initially biopsied, the net cost saving would be approximately $1.2 million with minimal added complications while still treating high-risk tumors. CONCLUSIONS: Routine RMB before intervention results in cost-saving and complication avoidance. Given the limitations of biopsy, shared decision-making is mandatory. Biopsy should be considered prior to intervention in at-risk populations.

Identification of oncological characteristics associated with improved overall survival in patients with adrenocortical carcinoma treated with adjuvant radiation therapy: Insights from the National Cancer Database.

OBJECTIVES: To test for an association between oncological risk factors and overall survival in patients with non-metastatic adrenocortical carcinoma treated with adjuvant radiation therapy at high-risk for recurrence per NCCN guidelines. MATERIALS AND METHODS: We analyzed data from patients undergoing surgical resection with or without aRT in the NCDB from 2004 to 2017. A multivariable Cox proportional hazards model was fit to assess for an association of aRT and OS. To determine whether aRT was associated with improved OS in patients with specific NCCN risk factors, we fit three multivariable Cox proportional hazard models with an interaction term between NCCN risk factors and the use of aRT. RESULTS: We identified 1,433 patients treated surgically for adrenocortical carcinoma with at least one risk factor. 259 patients received adjuvant radiation therapy (18%) while 1,174 (82%) patients did not. After adjustment, we noted a significant association between adjuvant radiation therapy and overall survival in the entire cohort in the multivariable Cox proportional hazards model (HR 0.68, 95% CI 0.55-0.85, P = 0.001). Adjuvant radiation therapy was associated with increased overall survival in patients with positive surgical margins (HR 0.47, 95% CI 0.35-0.65, P < 0.001), large tumor size ≥6 cm (HR 0.69, 95% CI 0.55-0.87, P = 0.002), and high-grade disease (HR 0.61, 95% CI 0.37-0.99, P = 0.046). CONCLUSIONS: Patients with ACC at high-risk for recurrence were associated with improved overall survival when treated with adjuvant radiation therapy. These data may help identify which patients should consider aRT after resection of clinically localized ACC.

Cystoscopy and Systematic Bladder Tissue Sampling in Predicting pT0 Bladder Cancer: A Prospective Trial.

PURPOSE: Concern for discordance between clinical staging and final pathology drives current management of patients deemed appropriate candidates for radical cystectomy. Therefore, we set out to prospectively investigate reliability and shortcomings of cystoscopic evaluation in radical cystectomy candidates. MATERIALS AND METHODS: Patients undergoing radical cystectomy for urothelial carcinoma were enrolled in a prospective single-arm study to evaluate reliability of Systematic Endoscopic Evaluation in predicting pT0 urothelial carcinoma (NCT02968732). Systematic Endoscopic Evaluation consisted of cystoscopy and tissue sampling at the time of radical cystectomy. Systematic Endoscopic Evaluation results were compared to radical cystectomy pathology. The primary end point was the negative predictive value of Systematic Endoscopic Evaluation findings in predicting radical cystectomy pathology. RESULTS: A total of 61 patients underwent Systematic Endoscopic Evaluation and radical cystectomy. Indications included muscle invasive bladder cancer in 42 (68.9%) and high risk nonmuscle invasive bladder cancer in 19 (31.1%). In all, 38 (62.3%, 90.5% of patients with muscle invasive bladder cancer) received neoadjuvant chemotherapy. On Systematic Endoscopic Evaluation, 31 (50.8%) patients demonstrated no visual nor biopsy-based evidence of disease (seeT0), yet 16/31 (51.6%) harbored residual disease (>pT0), including 8 (8/31, 25.8%) with residual ≥pT2 disease upon radical cystectomy. The negative predictive value of Systematic Endoscopic Evaluation predicting a pT0 bladder was 48.4% (CI 30.2-66.9), which was below our prespecified hypothesis. Therefore, the trial was stopped for futility. CONCLUSIONS: Approximately 1 of 4 patients with seeT0 at the time of radical cystectomy harbored residual muscle invasive bladder cancer. These prospective data definitively confirm major limitations of endoscopic assessment for pT0 bladder cancer. Future work should focus on novel imaging and biomarker strategies to optimize evaluations before radical cystectomy for improved decision making regarding bladder preservation.

Sporadic Angiomyolipomas Growth Kinetics While on Everolimus: Results of a Phase II Trial.

PURPOSE: Everolimus decreases tumor volume of renal angiomyolipomas in patients with tuberous sclerosis. No prospective data are available regarding the effect of everolimus on the growth kinetics in patients with sporadic angiomyolipomas. We sought to determine the safety and efficacy of everolimus in the volumetric reduction of sporadic angiomyolipomas. MATERIALS AND METHODS: This multi-institutional, prospective, phase II trial, enrolled patients with 3 cm or larger sporadic angiomyolipomas who were candidates for surgical resection or percutaneous angioembolization. Patients received 10 mg everolimus daily for 4 planned 28-day cycles. Response was defined as a 25% or greater volumetric reduction of patient angiomyolipoma. Baseline, 4, 6 and 12-month volumetric analyses were performed using magnetic resonance imaging. Everolimus was discontinued in those with less than 25% volumetric reduction after 4 cycles. Those with 25% or greater volumetric reduction received 2 additional cycles. The primary outcomes were the efficacy of everolimus in the volumetric reduction of angiomyolipomas by 25% or more, and the safety and tolerability of everolimus. RESULTS: Overall 20 patients were enrolled at 5 centers. Of these patients 11 (55%) completed 4 cycles and 7 (35%) completed 6 cycles. Efficacy was demonstrated, with 10 of 18 (55.6%) patients exhibiting a 25% or greater reduction in tumor volume at 4 months (median 58.5%) and 10 of 14 (71.4%) patients exhibiting a 25% or greater reduction in tumor volume at 6 months (median 58.2%). Four (20%) patients were withdrawn due to protocol defined toxicities and 8 (40%) self-withdrew from the study due to side effects. CONCLUSIONS: Everolimus was effective in causing volumetric reduction of angiomyolipomas by 25% or greater in most patients but was associated with a high rate of treatment discontinuation.

Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer.

PURPOSE: The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS: Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS: Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use (P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer-specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION: H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

Defects in DNA Repair Genes Confer Improved Long-term Survival after Cisplatin-based Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer.

Cisplatin-based neoadjuvant chemotherapy (NAC) has demonstrated an overall survival (OS) benefit in muscle-invasive bladder cancer (MIBC). However, only a subset of patients (25-50%) have a pathologic complete response at cystectomy. Using a cohort of 58 patients from two phase 2 trials, our group previously reported that mutations in the ATM, RB1, and FANCC genes correlate with complete response to cisplatin-based NAC, and consequently improve OS and disease-specific survival (DSS). These trials enrolled patients with T2-4 (N0 or N1) MIBC and treated them with accelerated/dose-dense NAC with methotrexate, vinblastine, adriamycin, and cisplatin, or gemcitabine and cisplatin, with a plan for curative cystectomy. Updated long-term follow-up (median 74 mo) shows that significantly greater OS and DSS was maintained for patients with ATM, RB1, or FANCC mutations. The 5-yr survival rate for patients with at least one mutation was 85%, compared to 45% for patients without a mutation. On the basis of the associations with response and long-term OS and DSS, we propose that these alterations may be useful as predictive biomarkers to allow clinicians to prioritize patients who are most likely to benefit from NAC before radical cystectomy. PATIENT SUMMARY: In this report we looked at outcomes for patients with muscle-invasive bladder cancer treated with cisplatin-based chemotherapy before surgery (neoadjuvant) who had mutations in a set of DNA damage repair genes (ATM, RB1, FANCC) compared to those who did not. We found that patients who had at least one mutation in one of these genes survived longer after receiving cisplatin chemotherapy before surgery than patients who did not.