Survival benefit of chemotherapy in a contemporary cohort of metastatic urachal carcinoma

Background: We relied on the most contemporary Surveillance, Epidemiology, and End Results (SEER) database and tested the hypothesis that chemotherapy may improve survival in metastatic urachal carcinoma (m-UraC). Material and Methods: Within the SEER database (2004\u20132016), we identified m-UraC patients aged 65 18 years. Propensity score matching (PSM: cystectomy status, age and sex), Kaplan-Meier plots, cumulative incidence plots, Cox regression models and competing risks regression (CRR) models addressed overall mortality (OM) and cancer-specific mortality (CSM). Results: Overall, 274 m-UraC patients were identified with a median age of 70 years. Most were male (66%) and Caucasian (72%). Overall, 32% received chemotherapy. Chemotherapy-exposed patients were younger (62 vs. 73 years, p<0.001) and more frequently underwent cystectomy (19 vs. 8%, P = 0.014). In 274 m-UraC patients, median OM and CSM were 6 (4 \u201310) months and 8 (6 \u201314) months, respectively. After 1:1 PSM, chemotherapy-exposed patients exhibited lower OM (median 16 vs. 3 months; multivariable HR 0.38, P <0.001) and lower CSM (median 17 vs. 4 months; multivariable CRR HR 0.52, P = 0.001). The association between chemotherapy and better survival was even stronger in younger ( 6470 years) patients (OM HR: 0.23, P <0.001; CSM CRR HR: 0.42, P = 0.001), but not in older ( 6571 years) patients (OM HR: 0.61, P = 0.2; CSM CRR HR: 1.02, P = 1), after PSM and multivariable adjustments. Conclusion: Overall, we validated the very aggressive nature of UraC, when distant metastases are present, and observed that m-UraC patients exposed to chemotherapy exhibited lower OM and CSM

Plasmacytoid variant urothelial carcinoma of the bladder: effect of radical cystectomy and chemotherapy in non-metastatic and metastatic patients

Purpose: Data about optimal management of plasmacytoid (PCV) bladder cancer patients are extremely scarce and limited by sample size. We focused on PCV bladder cancer patients to explore the effect of radical cystectomy (RC) and chemotherapy in non-metastatic (T 2\u20134N0\u20133M0), as well as in metastatic (TanyNanyM1) subgroups. Methods: Using the Surveillance, Epidemiology and End Results database (2000\u20132016), we identified 332 PCV patients with muscle-invasive disease or higher ( 65 T2N0M0). Kaplan\u2013Meier plots and Cox regression models addressed cancer-specific mortality (CSM). Results: In 332 PCV patients, median age was 68 years (Interquartile range [IQR]:58\u201376). Of those, 252 were non-metastatic patients (76%) vs 80 were metastatic patients (24%), at presentation. Of non-metastatic patients, 142 (56%) underwent RC and 131 (52%) underwent chemotherapy. Chemotherapy did not improve CSM in non-metastatic PCV. Conversely, RC was associated with lower CSM (hazard ratio [HR]: 0.51, p = 0.002). Median CSM-free survival was 48 vs 38 months for RC treated vs RC not treated. Of metastatic patients, 22 (28%) underwent RC and 42 (52%) underwent chemotherapy. Both chemotherapy and RC improved CSM in metastatic PCV. Median CSM-free survival was 12 vs 7 months for RC treated vs RC not treated (HR: 0.27, p < 0.001). Median CSM-free survival was 11 vs 4 months for chemotherapy exposed vs chemotherapy na\uefve (HR: 0.32, p = 0.002). Conclusions: Although RC resulted in lower CSM, chemotherapy failed to show that effect in non-metastatic PCV patients. Conversely, both chemotherapy and RC resulted in statistically significantly lower CSM in metastatic PCV patients

Survival after Radical Prostatectomy versus Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer

none16Purpose: Our goal was to compare cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer NetworknoneChierigo F.; Wenzel M.; Wurnschimmel C.; Flammia R.S.; Horlemann B.; Tian Z.; Saad F.; Chun F.K.H.; Graefen M.; Gallucci M.; Shariat S.F.; Mantica G.; Borghesi M.; Suardi N.; Terrone C.; Karakiewicz P.I.Chierigo, F.; Wenzel, M.; Wurnschimmel, C.; Flammia, R. S.; Horlemann, B.; Tian, Z.; Saad, F.; Chun, F. K. H.; Graefen, M.; Gallucci, M.; Shariat, S. F.; Mantica, G.; Borghesi, M.; Suardi, N.; Terrone, C.; Karakiewicz, P. I

Immuno-oncology therapy in metastatic bladder cancer: A systematic review and network meta-analysis

reserved15Context: Three first line and three second-line clinical trials tested the effect of immunotherapy (IO) relative to standard chemotherapy (CT) on overall survival. However, network meta-analysis-based comparisons have not yet been presented. We addressed this void. Objective: To provide comparisons of overall survival (OS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), objective response rates (ORR), disease control rates (DCR) and adverse events (AEs) associated with 1st and 2nd line IO-based regimens. Materials and methods: PubMed was searched for phase III randomized controlled trials from 2016 to 2021, including conference abstracts. We identified three first line [IMvigor130 (atezolizumab + CT vs atezolizumab vs CT), DANUBE (durvalumab vs durvalumab + tremelimumab vs CT), and KEYNOTE-361 (pembrolizumab + CT vs pembrolizumab vs CT)] and two second line [KEYNOTE-045 (pembrolizumab vs CT) and IMvigor211 (atezolizumab vs CT)] RCTs. Results: Overall, 3255 and 1452 patients were respectively included in the first- and second-line settings. In 1st line setting, compared with CT, no IO-based regimen exhibited survival benefit. However, all exclusive IO regimens resulted in lower rates of grade 3+ AEs. In 2nd line setting, compared with CT, only pembrolizumab improved OS benefit. Conversely, atezolizumab only showed OS benefit in exploratory analyses. Compared to second-line CT, no experimental regimen (atezolizumab or pembrolizumab) exhibited statistically significant ORR benefit. Both pembrolizumab and atezolizumab resulted in lower rates of grade 3+ AEs compared to 2nd line CT. Conclusions: In metastatic UC, IO-based regimens do not hold a survival benefit relative to CT in 1st line setting. However, pembrolizumab holds a survival benefit in 2nd line compared to CT. Several IO-based clinical trials are ongoing and will provide more and possibly better treatment alternatives for locally advanced and metastatic UC.mixedChierigo F.; Wenzel M.; Wurnschimmel C.; Flammia R.S.; Horlemann B.; Tian Z.; Saad F.; Chun F.K.H.; Tilki D.; Shariat S.F.; Gallucci M.; Borghesi M.; Suardi N.; Terrone C.; Karakiewicz P.I.Chierigo, F.; Wenzel, M.; Wurnschimmel, C.; Flammia, R. S.; Horlemann, B.; Tian, Z.; Saad, F.; Chun, F. K. H.; Tilki, D.; Shariat, S. F.; Gallucci, M.; Borghesi, M.; Suardi, N.; Terrone, C.; Karakiewicz, P. I

Radical Cystectomy vs. Radiotherapy in Urothelial Bladder Cancer in Elderly and Very Elderly Patients

Introduction: Controversy regarding cancer-specific mortality (CSM) of elderly and very elderly patients with muscle-invasive, non-metastatic, urothelial carcinoma of the urinary bladder (UCUB) undergoing radical cystectomy (RC) vs radiotherapy (RT) still exists. Materials and Methods: In the 2004-2016 Surveillance, Epidemiology and End Results (SEER) database, we identified 2663 UCUB patients aged 75-79 (1808 RC vs 855 RT) and 3569 UCUB patients aged 80-89 (1551 RC vs 2018 RT). After stratification for concomitant chemotherapy, propensity score matching (PSM) between RC and RT was applied and competing-risks regression models addressed CSM and OCM. Results: In the cohort aged 75-79, five-year CSM rates were 22.0 vs 49.0% for RC only vs RT only and yielded a HR of 0.41 (95% confidence interval (CI) 0.30-0.57, p<0.001) favoring RC only. Five-year CSM rates were 28.3 vs 44.3% for RC with chemotherapy vs trimodal therapy (TMT) and yielded a HR of 0.48 (95% CI 0.35-0.65, p<0.001) favoring RC with chemotherapy. In the cohort aged 80-89, five-year CSM rates were 24.2 vs 48.9% for RC only vs RT only and yielded a HR of 0.42 (95% CI 0.33-0.52, p<0.001) favoring RC only. Five-year CSM rates were 19.6 vs 43.2% for RC with chemotherapy vs TMT and yielded a HR of 0.43 (95% CI 0.28-0.67, p<0.001) favoring RC with chemotherapy. Conclusions: In elderly and very elderly patients, radical cystectomy is associated with virtually half the CSM rate than radiotherapy, regardless of concomitant chemotherapy administration

Life expectancy in metastatic urothelial bladder cancer patients according to race/ethnicity

Purpose: to compare observed overall survival vs age-adjusted lifetable (LT) derived life expectancy (LE) in metastatic urothelial bladder cancer (MBCa) patients according to race/ethnicity. Methods: We identified Caucasian, African American, Hispanic/Latino and Asian metastatic urothelial bladder cancer patients from 2004 to 2011 within the Surveillance, Epidemiology and End Results database. Social Security Administration tables were used to compute 5 year LE. LT-derived LE was compared to observed overall survival OS. Additionally, we relied on Poisson regression plots to display cancer-specific mortality (CSM) relative to other-cause mortality (OCM) for each race/ethnicity. Results: Overall, 2286 MBCa patients were identified. Of those, 1800 (79%) were Caucasian vs 212 (9.3%) African American vs 189 (8.3%) Hispanic/Latino vs 85 (3.7%) Asians. The median age at diagnosis was 71 years for Asians vs 70 for Caucasians vs 67 for Hispanic/Latinos vs 67 for African Americans. African Americans showed the biggest difference between observed OS and LT-predicted LE at five years (− 83.8%), followed by Hispanic/Latinos (− 81%), Caucasians (− 77%) and Asian patients (− 69%). In Poisson regression plots, Hispanic/Latinos displayed the highest cancer-specific mortality rate (88%), while African/Americans showed the highest other cause mortality rate (12%). Conversely, Asian patients displayed the lowest CSM rate (83%) and second lowest OCM rate (7%). Conclusions: African Americans showed the least favorable survival profile in MBCa, despite being youngest at diagnosis. Contrarily, Asians displayed the best survival profile in MBCa, despite being oldest at diagnosis

Effect of chemotherapy in metastatic prostate cancer according to race/ethnicity groups

Background: No North-American study tested the survival benefit of chemotherapy in de novo metastatic prostate cancer according to race/ethnicity. We addressed this void. Methods: We identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results database (2014–2015). Separate and specific Kaplan–Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed versus chemotherapy-naïve patients in four race/ethnicity groups: Caucasian versus African-American versus Hispanic/Latino vs Asian. Race/ethnicity specific propensity score matching was applied. Here, additional landmark analysis was performed. Results: Of 4232 de novo metastatic prostate cancer patients, 2690 (63.3%) were Caucasian versus 783 (18.5%) African-American versus 504 (11.8%) Hispanic/Latino versus 257 (6.1%) Asian. Chemotherapy rates were: 21.3% versus 20.8% versus 21.0% versus 20.2% for Caucasians versus African-Americans versus Hispanic/Latinos versus Asians, respectively. At 30 months of follow-up, overall survival rates between chemotherapy-exposed versus chemotherapy-naïve patients were 61.5 versus 53.2% (multivariable hazard ratio [mHR]: 0.76, 95 confidence interval [CI]: 0.63–0.92, p = 0.004) in Caucasians, 55.2 versus 51.6% (mHR: 0.76, 95 CI: 0.54–1.07, p = 0.11) in African-Americans, 62.8 versus 57.0% (mHR: 1.11, 95 CI: 0.73–1.71, p = 0.61) in Hispanic/Latinos and 77.7 versus 65.0% (mHR: 0.31, 95 CI: 0.11–0.89, p = 0.03) in Asians. Virtually the same findings were recorded after propensity score matching within each race/ethnicity group. Conclusions: Caucasian and Asian de novo metastatic prostate cancer patients exhibit the greatest overall survival benefit from chemotherapy exposure. Conversely, no overall survival benefit from chemotherapy exposure could be identified in either African-Americans or Hispanic/Latinos. Further studies are clearly needed to address these race/ethnicity specific disparities

Radiation therapy after radical prostatectomy is associated with higher other-cause mortality

Purpose: To test the association between external beam radiotherapy (EBRT) after radical prostatectomy (RP) vs RP only on rates of other-cause mortality (OCM) in men with prostate cancer (PCa). Patients and methods: Within the 2004–2016 Surveillance, Epidemiology, and End Results database, we identified 181,849 localized PCa patients, of whom 168,041 received RP only vs 13,808 who received RP + EBRT. Cumulative incidence plots displayed OCM between RP vs RP + EBRT after propensity score matching for age, PSA, clinical T- and N-stages, and biopsy Gleason scores. Multivariable competing risks regression models addressed OCM, accounting prostate cancer-specific mortality (CSM) as a competing event. Stratifications were made according to low- vs intermediate- vs high-risk groups and additionally according to age groups of ≤ 60, 61–70, and ≥ 71 years, within each risk group. Results: In low-, intermediate-, and high-risk patients, RP + EBRT rates were 2.7, 5.4 and 17.0%, respectively. After matching, 10-year OCM rates between RP and RP + EBRT were 7.7 vs 16.2% in low-, 9.4 vs 13.6% in intermediate-, and 11.4 vs 13.5% in high-risk patients (all p < 0.001), which, respectively, resulted in multivariable HR of 2.1, 1.3, and 1.2 (all p < 0.001). In subgroup analyses, excess OCM was recorded in low-risk RP + EBRT patients of all age groups (all p ≤ 0.03), but only in the older age group in intermediate-risk patients (61–70 years, p = 0.03) and finally, only in the oldest age group in high-risk patients (≥ 71 years, p = 0.02). Conclusion: Excess OCM was recorded in patients exposed to RT after RP. Its extent was most pronounced in low-risk patients, decreased in intermediate-risk patients, and was lowest in high-risk patients