Small Cell Bladder Cancer: Treatment Patterns for Local Disease and Associated Outcomes. A Retrospective Cohort Study.

BACKGROUND: Small cell bladder cancer (SCBC) is a rare histologic subtype with relative paucity of data regarding treatment response and outcomes. We reviewed 2 databases to compare outcomes in patients with localized SCBC treated with cystectomy versus concurrent chemoradiotherapy (CCRT). We hypothesized that survival would be similar with these therapy approaches. METHODS: We retrospectively reviewed our institutional and SEER-Medicare databases to identify patients with SCBC. Overall survival (OS) was determined from the date of diagnosis to last follow-up/death. For those with nonmetastatic disease, a multivariate Cox analysis was used to compare locoregional therapy with neoadjuvant chemotherapy (NAC) + cystectomy versus CCRT. RESULTS: We identified 53 patients in our institutional database and 1166 patients in SEER-Medicare with localized SCBC. Median OS (mOS) with NAC + cystectomy was 46 months (95% CI, 21-72) and 45 months (95% CI, 0-104) in the institutional and SEER-Medicare databases, respectively, whereas mOS with CCRT was 26 months (95% CI, 5-47) and 23 months (95% CI, 18-28) in the 2 series, respectively. In multivariate analysis, NAC followed by cystectomy was associated with an approximately 30% reduction in mortality compared to CCRT in both institutional and national databases but did not reach statistical significance (Institution HR 0.71, 95% CI, 0.22-2.4, P = .58; SEER HR 0.73, 95% CI, 0.49-1.08; P = .11). CONCLUSIONS: SCBC is very aggressive with limited survival observed in our institutional and SEER-Medicare datasets regardless of locoregional therapy used. There is an unmet need to define the optimal locoregional therapy for nonmetastatic stage and identify novel therapeutic targets.

Adjuvant Chemotherapy and Survival After Radical Cystectomy in Histologic Subtype Bladder Cancer.

OBJECTIVES: Patients with histologic subtype bladder cancer (HSBC) suffer worse outcomes than those with conventional urothelial carcinoma (UC). We sought to characterize the use of adjuvant chemotherapy (AC) in HSBC after radical cystectomy (RC) using the National Cancer Database (NCDB). MATERIALS AND METHODS: We retrospectively queried the NCDB (2006-2019) for patients with non-metastatic bladder cancer (BC) who underwent RC (N = 45,797). Patients were stratified by histologic subtype and receipt of AC. Multivariable logistic regression determined associations of demographic and clinicopathologic features with receipt of AC. Multivariable Cox regression evaluated associations between receipt of any AC and overall survival (OS). RESULTS: We identified 4,469 patients with HSBC classified as squamous, adenocarcinoma, small cell, sarcomatoid, micropapillary, or plasmacytoid. Squamous comprised 31% of the HSBC cohort, followed by small cells and micropapillary. Black patients were presented with a higher prevalence of adenocarcinoma (119/322, 37.0%). Use of AC was highest in plasmacytoid and small cell (30% each) and lowest in squamous (11%). Neuroendocrine histology was independently associated with greater odds of receiving AC (HR 1.6, 95% CI 1.37-1.87), while squamous cell histology was associated with lower odds (HR 0.61, 95% CI 0.53-0.71). On multivariable Cox regression analysis, treatment with AC was associated with significantly longer OS (HR 0.69, 95% CI 0.59-0.81) and for squamous, sarcomatoid, and micropapillary cohorts after stratified by subtype. CONCLUSIONS: AC was variably used among patients with HSBC and was associated with OS benefit in such patients.

Patterns of chemotherapy use with primary radiotherapy for localized bladder cancer in patients 65 or older.

Introduction: Bladder preservation with concurrent chemoradiotherapy after maximum transurethral resection of bladder tumor is an alternative to radical cystectomy in select patients with muscle invasive bladder cancer (MIBC). Concurrent administration of radio-sensitizing chemotherapy and radiation therapy (RT) has been shown to have superior disease control compared with RT alone and can often be administered with modest added toxicity. We sought to describe national patterns of chemotherapy use. Methods: The linked surveillance, epidemiology, and end results (SEER)-Medicare database was used to identify patients with cT2-4, N0/X, M0/X BC who received radiation between 2004 and 2018. Data on demographics, clinicopathologic factors, therapy and outcomes were extracted. Concurrent utilization of chemotherapy with RT was also identified (CRT). Multivariate logistic regression (MVA) models were used to explore factors associated with receipt of chemotherapy and overall survival (OS). Results: 2190 patients met inclusion criteria. Of these, 850 (38.8%) received no chemotherapy. Among those receiving chemotherapy, the most frequent regimens were single agent carboplatin, cisplatin, or gemcitabine. Factors that were independently associated with decreased likelihood of chemotherapy use were increasing age (OR 0.93, CI 0.92 - 0.95), Hispanic race (compared with White, OR 0.62, CI 0.39 - 0.99), cT3 or T4 (compared with cT2, OR 0.70, CI 0.55 - 0.90), and lower National Cancer Institute comorbidity index (OR 0.60, CI 0.51 - 0.70) (p < 0.05). Variables independently associated with increased likelihood of receipt of chemotherapy were married status (OR 1.28, CI 1.06 - 1.54), higher socioeconomic status (OR 1.31, CI 1.06 - 1.64), and later year of diagnosis (OR 1.09, CI 1.06 - 1.12). Receipt of concurrent chemotherapy with RT was associated with superior OS compared with RT alone. Conclusion: Over a third of patients >/65 years old receiving curative-intent RT for MIBC do not receive concurrent chemotherapy. Considering the improvement in oncologic outcomes with CRT over RT alone and more options, such as low dose gemcitabine which can be administered with modest toxicity, efforts are needed to identify barriers to utilization and increase the use of radio-sensitizing chemotherapy.

The Current Status of Palliative Care, Hospice, and End-of-Life Health Care Utilization in Patients With Malignant Ureteral Obstruction.

INTRODUCTION: Malignant ureteral obstruction is associated with a poor prognosis, with a median survival of 3 to 7 months. These patients are ideal candidates for concurrent palliative care services, consistent with American Society of Clinical Oncology guidelines. We aimed to characterize palliative care, hospice, and end-of-life health care utilization in patients with malignant ureteral obstruction. METHODS: Patients ≥ 18 years old at our institution and diagnosed with malignant ureteral obstruction between May 2014 and August 2020 were retrospectively identified and pertinent data extracted. Palliative care, hospice, and end-of-life health care utilization was described, and factors associated with each were assessed with logistic regression models. Overall survival was assessed with Cox proportional hazard regression models. RESULTS: One hundred fifteen patients qualified for analysis; 39.1% (45/115) utilized palliative care and spent a median of 12.5 days (IQR 3-52 days) on nonhospice palliative care. On adjusted analysis Black ethnicity (aOR 3.44, 95% CI: 1.08-10.94) was associated with palliative care utilization. Of the patients, 53.9% (62/115) utilized hospice. The median time from hospice initiation to death was 12 days (IQR 5-23 days). On adjusted analysis, prior extirpative surgery (aOR 3.63, 95% CI 1.01-13.05) and palliative care utilization (aOR 4.38, 95% CI 1.70-11.31) were associated with hospice utilization. Median survival following diagnosis was 141 days (IQR 37.5-442.5). Of the patients, 43.0% (37/86) had high end-of-life health care utilization. On multivariable analysis, only hospice (aOR 0.03, 95% CI 0.01-0.14) was associated with less end-of-life health care utilization. CONCLUSIONS: Palliative care is underutilized in malignant ureteral obstruction. Hospice, but not palliative care utilization, was associated with decreased end-of-life health care utilization.

A prostate biopsy risk calculator based on MRI: development and comparison of the Prospective Loyola University multiparametric MRI (PLUM) and Prostate Biopsy Collaborative Group (PBCG) risk calculators.

OBJECTIVES: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC. PATIENTS AND METHODS: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts. RESULTS: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05). CONCLUSIONS: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa.

Percentage of sarcomatoid histology is associated with survival in renal cell carcinoma: Stratification and implications by clinical metastatic stage.

PURPOSE: Sarcomatoid dedifferentiation in renal cell carcinoma (RCC) represents an aggressive histology where degree of sarcomatoid histology (SH) may impact prognosis for cM0 and cM1 patients. We aimed to evaluate the association of percentage of SH with survival. MATERIALS AND METHODS: Patients ≥18 years old diagnosed with RCC with any degree of SH after nephrectomy were included (2005-2020) from a single-center. Associations of degree of SH and cM stage with overall survival (OS) and recurrence-free survival (RFS) were evaluated by Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: One hundred twenty-eight patients were included with 80 (62.5%) cM0 and 48 (37.5%) cM1. cM1 patients were more likely to be male with higher clinical T stage (P = 0.001) than cM0, but a similar proportion had ≥20% SH (47.9% vs. 42.5%, P = 0.55). With median 19.4 months follow-up, SH was associated with worse OS per 10% increase (hazard ratio [HR] 1.12 [95% confidence interval {CI} 1.03-1.23], P = 0.009) and a ≥20% cutoff (HR 2.87 [95% CI 1.27-6.47], P = 0.01). Patients with cM0 disease and <20% SH had better 2-year OS (81.4%) compared to cM0 and ≥20% SH (44.8%) or cM1 patients who received nephrectomy (54.8%). Tumor size was also an independent predictor. Sites of distant metastasis and lines of therapy were similar for metachronous and synchronous patients. SH stratified 2-year RFS (cM0: 70.2% for <20% SH vs. 32.1% for ≥20% SH). CONCLUSIONS: SH in RCC is independently associated with OS and RFS. Patients who are cM0 with any SH may be candidates for adjuvant immunotherapy while those with ≥20% SH likely carry micrometastatic disease and should receive closer surveillance.

Robotic-assisted tumor enucleation versus standard margin partial nephrectomy: Perioperative, renal functional, and oncologic outcomes for low and intermediate complexity renal masses.

PURPOSE: Standard margin partial nephrectomy (SPN) with sharp incision across normal renal parenchyma carries perioperative morbidity and renal functional implications. Tumor enucleation (TE) is an alternative approach using a natural plane of dissection around the tumor pseudocapsule to maximize parenchymal preservation. We compared perioperative, functional, and oncologic outcomes for robotic-assisted TE to SPN. MATERIALS AND METHODS: Patients ≥18 years of age undergoing robotic-assisted TE or SPN were included (2008-2020). Baseline demographics and tumor characteristics were compared. Perioperative, renal functional, and oncologic outcomes were assessed for comparative effectiveness. RESULTS: A total of 467 patients were included with 176 (37.7%) TE and 291 (62.3%) SPN. Baseline characteristics and final histology were comparable; 18% of patients had baseline stage 3 chronic kidney disease. TE had lower median blood loss, operative time, length of stay, and fewer complications compared to SPN. Positive margin rates were higher for TE vs. SPN (8.5% vs. 3.4%, P = 0.04) with similar recurrence rates (2.3% vs. 3.4%, P = 0.48) and no difference in cancer-specific or overall survival with median 4.0 years follow-up. Baseline estimated glomerular filtration rate was comparable (76.1 vs. 78.2, P = 0.63) while renal function in the first year was better preserved with TE (74.6 vs. 68.1, P < 0.001) showing an 8-point estimated glomerular filtration rate (P = 0.001) advantage after adjustment. The rate of stage ≥3 chronic kidney disease by 12 months was lower for TE compared to SPN (21.5% vs. 34.1%, P = 0.006). CONCLUSIONS: TE is an alternative approach to SPN associated with favorable perioperative and renal functional outcomes. While positive margin rates are higher, longer-term recurrence rates are no different suggesting pseudocapsule disruption during TE has limited impact on oncologic outcomes.

Four versus 3 Cycles of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: Implications for Pathological Response and Survival.

PURPOSE: The ideal number of neoadjuvant chemotherapy (NAC) cycles for muscle-invasive bladder cancer is uncertain with 3 to 4 representing the standard of care (SOC). We compared ypT0 rates and survival between patients receiving 4 versus 3 cycles of NAC with evaluation of chemotherapy-related toxicity for correlation with tumor chemosensitivity and pathological response. MATERIALS AND METHODS: Patients receiving NAC followed by radical cystectomy for cT2-4N0M0 urothelial carcinoma from 2 institutions were included. Primary study groups included 4 cisplatin-based NAC cycles, 3 cisplatin-based NAC cycles, and nonSOC NAC (1-2 cycles or noncisplatin-based) to compare ypT0/≤ypT1 rates and survival. A cohort of patients not receiving NAC was included for pathological reference. RESULTS: Of 693 total patients, 318 (45.9%) received NAC. ypT0 and ≤ypT1 rates were 42/157 (26.8%) and 86/157 (54.8%) for 4 cycles, 38/114 (33.3%) and 71/114 (62.3%) for 3 cycles, and 6/47 (12.8%) and 13/47 (27.7%) for nonSOC (p=0.03 and p <0.01, respectively). Pathological response appeared higher among patients receiving 3 cycles due to toxicity (ypT0: 29/77 [37.7%]; ≤ypT1: 51/77 [66.2%]) but did not reach statistical significance. Toxicities leading to treatment modifications were thrombocytopenia (32.1%), neutropenia (27.2%), renal insufficiency (22.2%), and constitutional symptoms (18.5%). NonSOC patients had lower Kaplan-Meier survival (cT2-cT4N0M0: log-rank p=0.07; cT2N0M0: log-rank p=0.02). There were no statistically significant differences in survival between 4 and 3 cycles (HR 1.00 [95% CI 0.57-1.74], p=0.99). CONCLUSIONS: Patients completing 3 cycles of cisplatin-based NAC have similar pathologic response and short-term survival compared to 4 cycles. Further evaluation of patients experiencing toxicity as a potential marker of tumor chemosensitivity is needed.

Risk of prostate cancer for men with prior negative biopsies undergoing magnetic resonance imaging compared with biopsy-naive men: A prospective evaluation of the PLUM cohort.

BACKGROUND: Men with prior negative prostate biopsies have a lower risk of being diagnosed with prostate cancer in comparison with biopsy-naive men. However, the relative clinical utility of identified lesions on multiparametric magnetic resonance imaging (mpMRI) is uncertain between the 2 settings. METHODS: Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015 to June 2020) were examined. The detection of any prostate cancer and clinically significant prostate cancer (Gleason score ≥ 3 + 4) was stratified by Prostate Imaging-Reporting and Data System (PI-RADS) scores in the prior negative and biopsy-naive settings. Multivariable logistic regression models (PLUM models) assessed predictors, and decision curve analyses were used to estimate the clinical utility of PI-RADS cutoffs relative to the models. RESULTS: Nine hundred men (420 prior negative patients and 480 biopsy-naive patients) were included. Prior negative patients had lower risks of any prostate cancer (27.9% vs 54.4%) and clinically significant prostate cancer (20.0% vs 38.3%) in comparison with biopsy-naive patients, and this persisted when they were stratified by PI-RADS (eg, PI-RADS 3: 13.6% vs 27.4% [any prostate cancer] and 5.2% vs 15.4% [clinically significant prostate cancer]). The rate of detection of clinically significant prostate cancer was 5.3% among men with prior negative biopsy and PI-RADS ≤ 3. Family history and Asian ancestry were significant predictors among biopsy-naive patients. PLUM models demonstrated a greater net benefit and reduction in biopsies (45.8%) without missing clinically significant cancer in comparison with PI-RADS cutoffs (PI-RADS 4: 34.0%). CONCLUSIONS: Patients with prior negative biopsies had lower prostate cancer detection by PI-RADS score category in comparison with biopsy-naive men. Decision curve analyses suggested that many biopsies could be avoided by the use of the PLUM models or a PI-RADS 4 cutoff without any clinically significant cancer being missed. LAY SUMMARY: Men with a prior negative prostate biopsy had a lower risk of harboring prostate cancer in comparison with those who never had a biopsy. This was true even when patients in each group had similar multiparametric magnetic resonance imaging (mpMRI) findings in terms of Prostate Imaging-Reporting and Data System (PI-RADS)-graded lesions. Decision curve analyses showed that many biopsies could be avoided by the use of the Prospective Loyola University mpMRI prediction models or a PI-RADS 4 cutoff for patients with prior negative biopsies.

Systematic versus Targeted Magnetic Resonance Imaging/Ultrasound Fusion Prostate Biopsy among Men with Visible Lesions.

PURPOSE: Multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion-guided biopsy may improve prostate cancer (PCa) detection and reduce grade misclassification. We compared PCa detection rates on systematic, magnetic resonance imaging-targeted, and combined biopsy with evaluation of important subgroups. MATERIALS AND METHODS: Men with clinical suspicion of harboring PCa from 2 institutions with visible Prostate Imaging-Reporting and Data System (PI-RADSTMv2) lesions receiving mpMRI-US fusion-guided prostate biopsy were included (2015-2020). Detection of PCa was categorized by grade group (GG). Clinically-significant PCa (csPCa) was defined as ≥GG2. Patients were stratified by biopsy setting and PI-RADS. RESULTS: Of 1,236 patients (647 biopsy-naïve) included, 626 (50.6%) harbored PCa and 412 (33.3%) had csPCa on combined biopsy. Detection of csPCa was 27.9% vs 23.3% (+4.6%) and GG1 PCa was 11.3% vs 17.8% (-6.5%) for targeted vs systematic cores. Benefit in csPCa detection was higher in the prior negative than biopsy-naïve setting (+7.8% [p <0.0001] vs +1.7% [p=0.3]) while reduction in GG1 PCa detection remained similar (-5.6% [p=0.0002] vs -7.3% [p=0.0001]). Targeted biopsy showed increased csPCa detection for PI-RADS 5, decrease in GG1 for PI-RADS 3, and both for PI-RADS 4 relative to systematic biopsy. Combined biopsy detected more csPCa (+10.0%) and slightly fewer GG1 PCa (-0.5%) compared to systematic alone. Upgrading to ≥GG2 by targeted biopsy occurred in 9.8% with no cancer and 23.6% with GG1 on systematic biopsy. CONCLUSIONS: Combined biopsy doubled the benefit of targeted biopsy alone in detection of csPCa without increasing GG1 PCa diagnoses relative to systematic biopsy. Utility of targeted biopsy was higher in the prior negative biopsy cohort, but advantages of combined biopsy were maintained regardless of biopsy history.

African American Men have Increased Risk of Prostate Cancer Detection Despite Similar Rates of Anterior Prostatic Lesions and PI-RADS Grade on Multiparametric Magnetic Resonance Imaging.

OBJECTIVE: To determine whether the frequency of anterior prostate lesions (APL) on multiparametric magnetic resonance imaging (mpMRI) prior to biopsy differed between African American (AA) and non-AA men and evaluate implications of race and tumor location for prostate cancer (PCa) detection. METHODS: Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015-December 2020) without prior diagnosis of PCa were evaluated for APLs by race. Multivariable logistic regression models evaluated predictors of APLs and associations of APLs and race with detection of any PCa (grade group 1+) and clinically significant PCa (csPCa; grade group 2+). Additional stratified and propensity score matched analyses were conducted. RESULTS: Of 1,239 men included, 190 (15.3%) were AA and 302 (24.4%) had at least one APL with no differences by race on multivariable analysis. While men with APLs were twice as likely to harbor PCa or csPCa, the unadjusted proportion of targeted biopsy-confirmed APL PCa (12.6% vs 12.0%) or csPCa (8.4% vs 8.9%) were similar for AA and non-AA men. AA men had higher risk of prostate cancer on targeted cores (OR 1.66 (95%CI 1.06 - 2.61), P = 0.026) which was independent of lesion location or PI-RADS. CONCLUSION: AA men were found to have similar rates of APLs on mpMRI to non-AA men indicating access to mpMRI may mitigate some of the historical racial disparity based on lesion location. AA men have increased risk of PCa detection compared to non-AA men independent of anterior location or lesion grade on mpMRI reinforcing the importance of identifying genetic, biologic, and socioeconomic drivers.

Management Trends in Pediatric Nonseminomatous Germ Cell Tumors.

OBJECTIVE: To characterize post-orchiectomy treatment trends in prepubescent and adolescent patients with nonseminomatous germ cell tumors (NSGCT) and identify patient and hospital factors associated with receiving surveillance or treatment (chemotherapy or RPLND) after orchiectomy. METHODS: Patients <18 years old diagnosed with NSGCT from 2006 to 2016 were extracted from the National Cancer Database. Patients were stratified into prepubescent (<12 years old) and adolescent (age 13-17) cohorts. National trends and multivariable logistic regression for odds of undergoing treatment were identified. RESULTS: Documentation of use of post-orchiectomy treatment or surveillance was available for 1006 patients. This population was divided into a prepubescent cohort (≤12 years of age, n = 153) and an adolescent cohort (13-17 years of age, n = 853). 545 (54.4%) patients proceeded with treatment. The proportion of patients undergoing treatment in each cohort remained similar over time, but there was a shift in the adolescent cohort away from RPLND towards chemotherapy. In the prepubescent cohort, pathologic stage group III was associated with undergoing treatment. Older age, >50 miles travel to treatment facility, and higher pathologic stage group were associated with treatment in the adolescent cohort. Black race was associated with decreased odds of undergoing treatment among adolescents. CONCLUSION: National treatment trends regarding NSGCT remained similar over a decade. Higher disease stage in prepubescent patients lead to additional post-orchiectomy treatment. Adolescents with NSGCT were more likely to undergo post-orchiectomy treatment if they were older, traveled farther to a treatment center, and had a higher disease stage.