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

IntroductionControversy 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 MethodsIn 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.ResultsIn 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.ConclusionsIn elderly and very elderly patients, radical cystectomy is associated with virtually half the CSM rate than radiotherapy, regardless of concomitant chemotherapy administration.     

Contemporary Trends and Efficacy of Pelvic Lymph Node Dissection at Radical Cystectomy for Urothelial and Variant Histology Carcinoma of the Urinary Bladder

ObjectiveTo test 1) contemporary pelvic lymph node dissection (PLND) trends at radical cystectomy (RC) in variant histology bladder cancer (VHBC) patients and urothelial carcinoma of the urinary bladder (UCUB), as well as 2) to test the effect of PLND extent on cancer specific mortality (CSM) after RC.MethodsWithin the Surveillance, Epidemiology and End Results Registry (SEER, 2004-2016), we identified non-metastatic stage T_1-2 or T_3-4 VHBC and UCUB patients, who underwent RC. CSM and lymph node invasion (LNI) rates were stratified according to PLND extent, as well as coded continuously in multivariate Cox and logistic regression models.ResultsOf 19,020 patients, 1736 (9.1%) were coded as having VHBC (46.9% squamous cell carcinoma, 22.5% adenocarcinoma, 18.9% neuroendocrine carcinoma, 11.7% not otherwise specified) vs 17,284 (90.9%) UCUB. PLND was performed in 80.1 of VHBC vs. 83.5% UCUB patients. In both histological groups, PLND rates increased over time (70.9-89.6% and 76.2%-90.1%, both P < .01). PLND extent did not significantly affect CSM in stage T_1-2 or T_3-4 VHBC patients. Conversely, PLND extent was associated with lower CSM in T_1-2, as well as in T_3-4 UCUB patients, which was confirmed in multivariate Cox analyses (Hazard ratio [HR] 0.99, P < .001). Rates of LNI increased with extent of PLND in logistic regression analyses in stage T_3-4 VHBC (Odds ratio [OR] 1.01, P = .001), stage T_1-2 UCUB (OR 1.01, P < .001) and T_3-4 UCUB (OR 1.01, P < .001), but not in stage T_1-2 VHBC (OR 1.01, P = .3).ConclusionPLND rates do not differ between VHBC and UCUB patients. A potential survival benefit related to more extensive PLND is operational in UCUB patients, but not in VHBC patients.     

Contemporary Assessment of Survival Rates in Stage I Testicular Seminoma: A Population-Based Comparison Between Surveillance and Active Treatment After Orchiectomy

BackgroundWe tested contemporary surveillance and active treatment (AT) that included chemotherapy (CHT) and radiotherapy (RT) rates for stage I testicular seminoma patients, as well as cancer-specific mortality (CSM) and other-cause mortality (OCM) rates.Patients and MethodsWithin the Surveillance, Epidemiology, and End Results database (1988-2015) we identified 11,206 stage I testicular seminoma patients. Surveillance versus CHT versus RT use rates were investigated using estimated annual percentage change (EAPC) analyses. After propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (MCRRMs) tested for CSM and OCM.ResultsOf all 11,206 patients, 4434 (40%), 918 (8%), and 5854 (52%), respectively, underwent surveillance, CHT, or RT after initial orchiectomy. Surveillance (EAPC: 7.5%; P < .001) and CHT (EAPC: 13.5%; P < .001) rates increased over time, whereas RT rates decreased (EAPC: ?3.8%; P < .001). After PS matching, in MCRRMs surveillance was an independent predictor of CSM, relative to AT (hazard ratio [HR], 2.59; P = .04). Conversely, surveillance versus AT did not affect OCM (HR, 1.52; P = .051). All other analyses that focused on CSM and OCM, namely surveillance versus RT, surveillance versus CHT, and RT versus CHT resulted in nonsignificant differences (all P > .5).ConclusionSurveillance and CHT use in stage I testicular seminoma rates increased, whereas RT rate decreased over time. A protective effect of AT defined as either RT or CHT was identified on CSM, relative to surveillance. This protective effect was not described for OCM. No differences in survival were recorded, when individual management strategies (surveillance vs. RT vs. CHT) were compared with each other.     

Survival After Partial Cystectomy for Variant Histology Bladder Cancer Compared With Urothelial Carcinoma: A Population-based Study

BackgroundThe present study tested cancer-specific (CSM) and overall mortality (OM) after partial cystectomy (PC) for variant histology bladder cancer (non–urothelial carcinoma of the urinary bladder UCUB), relative to UCUB and relative to radical cystectomy (RC).Materials and MethodsWithin the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with stage T1-T2N0M0 non-UCUB and UCUB who had undergone PC or RC. Non-UCUB included adenocarcinoma, squamous carcinoma, neuroendocrine carcinoma, and other histologic subtypes. First, CSM and OM after PC were compared between the non-UCUB and UCUB groups. Second, CSM and OM after PC were compared with RC in the non-UCUB group. Kaplan Meier plots and multivariable Cox regression models were used before and after inverse probability of treatment weighting.ResultsOverall, 248 patients (16.3%) treated with PC had had non-UCUB. Of the 248 cases, 115 (46.5%), 50 (20%), 34 (14%), and 49 (19.5%) were adenocarcinoma, squamous carcinoma, neuroendocrine carcinoma, and other histologic subtypes, respectively. The comparison between PC in the non-UCUB and PC in the UCUB group showed higher CSM (hazard ratio, 1.4; P = .03) but the same OM rates (hazard ratio, 1.1; P = .7) in the non-UCUB group. The comparison between PC and RC for the non-UCUB group showed no CSM or OM differences.ConclusionsPC for non-UCUB was associated with higher CSM compared with PC for UCUB. However, PC instead of RC for select patients with non-UCUB appears not to undermine cancer-control outcomes. Thus, the excess CSM is probably unrelated to cystectomy type but could originate from differences in the tumor biology. These results could act as hypothesis generating for the design of future trials.     

Radical cystectomy in non-metastatic sarcomatoid bladder cancer: A direct comparison vs urothelial bladder cancer

IntroductionThe effect of radical cystectomy (RC) on cancer-specific mortality (CSM) is unclear in non-metastatic sarcomatoid bladder cancer (SBC) patients. We aimed to test the benefit of RC in SBC, and to perform a direct comparison vs urothelial bladder cancer (UCB).Materials and methodsWithin the Surveillance, Epidemiology, and End Results database (SEER 2001–2018) all non-metastatic SBC and UBC patients were identified. Endpoint of interest was CSM. Propensity score matching (PSM), cumulative incidence plots, competing risks regression (CRR) analyses, three-months landmark analyses, and sensitivity analyses were performed. All results were stratified according to organ-confined (OC: T₂N₀M₀) vs non-organ-confined (NOC: T_3-4N₀M₀ or T_anyN_1-3M₀) stages.ResultsOf 554 SBC patients, 49 vs 51% harbored OC vs NOC stages. Of 47,741 UBC patients, 62 vs 38% harbored OC vs NOC stages. RC rates were 33 vs 67% in OC vs NOC-SBC patients, and 40 vs 60% in OC vs NOC-UBC patients. After 1:1 PSM, comparison between RC vs no-RC was performed in OC-SBC (67 patients per group), OC-UBC (7611 patients per group), NOC-SBC (63 patients per group), and NOC-UBC patients (4644 patients per group). CRR hazard ratios associated with RC vs no-RC were 0.37 (p < 0.001) in OC-SBC vs 0.45 (p < 0.001) in OC-UBC, and 0.56 (p = 0.01) in NOC-SBC vs 0.68 (p < 0.001) in NOC-UBC. These results were replicated in sensitivity and landmark analyses.ConclusionsThe protective effect of RC vs no-RC is stronger in SBC than UBC patients, regardless of OC vs NOC stages.     

Increasing Rates of Perioperative Chemotherapy are Associated With Improved Survival in Men With Urothelial Bladder Cancer With Prostatic Stromal Invasion

BackgroundOur objective was to test whether the rates of perioperative chemotherapy (CHT) administration in patients with urothelial bladder cancer (UCUB) with prostatic stromal invasion (pT4a) changed over time. Moreover, we tested the effect of CHT on overall mortality (OM), as well as on cancer-specific mortality (CSM) in this patient population.Materials and MethodsWithin the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 1513 men with non-metastatic UCUB with prostatic stromal invasion who underwent radical cystectomy with lymph node dissection, with or without CHT administration. Estimated annual percentage change analyses, inverse probability of treatment-weighting (IPTW), Kaplan-Meier plots, Cox regression models, and landmark analyses were performed.ResultsOverall, 732 (48.4%) patients with pT4a UCUB disease underwent radical cystectomy with perioperative CHT administration between 2004 and 2016. The CHT administration rate increased from 29.0% in 2004 to 64.8% in 2016 (P < .001). In IPTW-adjusted analyses, the 5-year overall survival was 47.7% versus 39.8%, and cancer-specific survival was 53.6 versus 50.1%, for with versus without CHT administration, respectively. After multivariable and IPTW-adjusted Cox regression models, administration of CHT independently predicted lower OM (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.52-0.73), as well as lower CSM (HR, 0.66; 95% CI, 0.55-0.80). even after 3-month landmark analyses (OM HR, 0.64; 95% CI 0.54-0.76; CSM HR, 0.70; 95% CI, 0.58-0.85).ConclusionsThe use of CHT in patients with pT4a UCUB increased from low to moderate in the most contemporary era. However, based on its impressive reduction in OM, as well as in CSM, further increases in CHT administration rates should be highly encouraged in this patient population.     

Conditional survival for non-metastatic muscle-invasive adenocarcinoma of the urinary bladder after radical cystectomy

PurposeTo test the effect of conditional survival on 36-months’ cancer-specific mortality (CSM)-free survival in non-metastatic muscle-invasive adenocarcinoma of the bladder (ACB).Materials and methodsWithin the Surveillance, Epidemiology, and End Results database (2000–2018), ACB patients treated with radical cystectomy (RC) were identified. Multivariable competing risks regression (CRR) analyses assessed the independent predictor status of organ-confined (OC, T₂N₀M₀) vs non-organ-confined stage (NOC, T_3-4N₀M₀ or T_anyN_1-3M₀) on CSM. Conditional 36-months’ CSM-free survival estimates were computed based on event-free intervals of 12, 24, 36, 48 and 60 months after RC, according to stage.ResultsOf 475 ACB patients, 132 (28%) harbored OC vs 343 (72%) harbored NOC stage. In multivariable CRR models, NOC vs OC stage independently predicted lower CSM (hazard ratio 3.55; 95% CI 2.66, 5.83; p < 0.001). Conversely, neither chemotherapy nor radiotherapy were independently associated with CSM. In OC stage, 36-months’ CSM-free survival rate was 84% at baseline. Provided event-free intervals of 12, 24, 36, 48 and 60 months, conditional 36-months’ CSM-free survival estimates were 84, 87, 87, 89 and 89%. In NOC stage, 36-months’ CSM-free survival rate was 47% at baseline. Provided event-free intervals of 12, 24, 36, 48 and 60 months, conditional 36-months’ CSM-free survival estimates were 51, 62, 69, 78 and 85%.ConclusionsConditional survival estimates provide better insight into survival of patients with longer event-free follow-up. In consequence, conditional survival estimates might be highly valuable for individual patient counselling.     

Survival of Contemporary Patients With Non-metastatic Small-cell Carcinoma of Urinary Bladder,According to Alternative Treatment Modalities

BackgroundThe objective of this study was to test the effect of chemotherapy and/or radical cystectomy (RC) and/or radiotherapy (RT) on survival of patients with non-metastatic small-cell carcinoma of the urinary bladder (SCCUB).Materials and MethodsWithin the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with non-metastatic (T1-4, N0, M0) SCCUB. Treatment was defined as: chemotherapy alone, chemotherapy + RC, and chemotherapy + RT. Temporal trends, cumulative incidence plots, and multivariable competing risks regression models were used.ResultsOf 595 patients with SCCUB, 230 (38.5%), 159 (27%), and 206 (34.5%) were treated with chemotherapy alone, chemotherapy + RC, and chemotherapy + RT, respectively. The rates of chemotherapy + RC increased (estimated annual percentage changes [EAPC], +5.9%; P = .002). Conversely, chemotherapy alone (EAPC, −1.7%; P = .1) and chemotherapy + RT rates decreased (EAPC: −2.2%; P = .08). Overall, 5-year cancer-specific mortality (CSM) rates were 44%, 29%, and 40% for patients treated with chemotherapy alone, chemotherapy + RC, and chemotherapy + RT, respectively (P = .004). Relative to chemotherapy alone, patients treated with chemotherapy + RC experienced lower CSM (hazard ratio, 0.5; P < .001). Conversely, patients treated with chemotherapy + RT did not exhibit any CSM benefit (hazard ratio, 0.8; P = .2), when compared with chemotherapy alone.ConclusionIn contemporary patients with SCCUB with non-metastatic disease, the rates of chemotherapy + RC are increasing. Conversely, the rates of combined chemotherapy with RT and chemotherapy alone are decreasing. These patterns of treatment are in agreement with better cancer control in patients with SCCUB. In consequence, until more robust data become available, the combination of chemotherapy and RC should represent the recommended treatment strategy.     

Bladder Cancer: A Comparison Between Non-urothelial Variant Histology and Urothelial Carcinoma Across All Stages and Treatment Modalities

BackgroundThe purpose of this study was to evaluate stage at presentation, treatment rates, and cancer-specific mortality (CSM) of non-urothelial variant histology (VH) bladder cancer (BCa) relative to urothelial carcinoma of the urinary bladder (UCUB).Materials and MethodsWithin the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), patients with VH BCa and UCUB were identified. Stage at presentation and treatment rates, as well as multivariably adjusted and matched CSM rates according to TNM stage within each histologic subtype, were reported.ResultsOf all 222,435 eligible patients with BCa, 11,147 (5.0%) harbored VH. Among those, squamous cell carcinoma accounted for 3666 (1.6%) patients, adenocarcinoma for 1862 (0.8%), neuroendocrine carcinoma for 1857 (0.8%), and other VH BCa for 3762 (1.7%) of the study cohort. Patients with VH BCa showed invariably more advanced TNM stage at presentation compared with patients with UCUB. Treatment rates according to TNM stages showed similar distribution of cystectomy rates in VH BCa and UCUB. However, important differences in the distribution of radiotherapy and chemotherapy rates existed within VH BCa and in comparison with UCUB. Furthermore, even after multivariable adjustment and matching with UCUB, squamous cell carcinoma exhibited higher CSM (hazard ratios, 1.43-1.95; all P < .01) across all stages. All other VH predominantly exhibited higher CSM than UCUB in either non–muscle-invasive or muscle-invasive nonmetastatic stages.ConclusionTNM stage at diagnosis is invariably more advanced in all patients with VH BCa versus patients with UCUB. Of all VH BCa, in multivariably adjusted stage for stage analyses, squamous cell carcinoma appears to have the worst natural history. All other VH subgroups exhibited more aggressive natural history than UCUB in nonmetastatic stages only.     

Contemporary use and survival after perioperative systemic chemotherapy in patients with locally advanced non-metastatic urothelial carcinoma of the bladder treated with radical cystectomy

BackgroundLocally advanced muscle-invasive bladder cancer (MIBC) patients who are candidates for radical cystectomy (RC) should receive perioperative chemotherapy (CHT). However, the adherence to CHT guidelines is low. Thus, we tested contemporary CHT use rates and associated cancer-specific mortality (CSM) and overall mortality (OM) rates.Materials and methodsWithin the SEER database (2004–2015), we identified pT3N0/+ MIBC patients, who underwent RC, with or without perioperative CHT. Estimated annual percentage changes (EAPCs) analyses were used. After inverse probability of treatment weighting (IPTW), Kaplan–Meier (KM) analyses and Cox regression models (CRMs) tested the association of CHT on survival in the overall population (n = 3817), as well as after stratification according to stage, gender and age. Landmark analyses tested for immortal time bias.ResultsOverall, 44.3% of patients received CHT. Between 2004 and 2015, CHT administration rates increased from 32.1% to 55.6% (EAPC: +6.0%; p < 0.001). In CRMs, CHT was associated with lower CSM (HR 0.73, CI 0.65–0.81) and OM (HR 0.69, CI 0.62–0.76). In sensitivity analyses, CHT was also associated with lower CSM and OM in N0 patients (CSM: HR 0.76, 95% CI 0.65–0.88; OM: HR 0.69, 95% CI 0.60–0.79) and in N+ patients (CSM: HR 0.69, 95% CI 0.59–0.80; OM: HR 0.67, 95% CI 0.58–0.77), as well as according to gender and age. Landmark analyses confirmed the above results.ConclusionsPerioperative CHT was associated with better survival and its rate of use increased in locally-advanced MIBC RC patients. The latter confirm one large observational study and several small prospective studies.     

Contemporary Assessment of Long-Term Survival Rates in Patients With Stage I Nonseminoma Germ-Cell Tumor of the Testis: Population-Based Comparison Between Surveillance and Active Treatment After Initial Orchiectomy

BackgroundHistorical data demonstrated similar survival outcomes in patients with stage I nonseminoma germ-cell tumor of the testis (NSGCTT) subjected to either surveillance or active treatment (AT) after orchiectomy. However, data with long-term follow-up are unavailable. We tested contemporary treatment rates and their effect on cancer-specific mortality (CSM) and other-cause mortality (OCM) relative to surveillance, as well as after stratification between chemotherapy (CHT) versus retroperitoneal lymph node dissection (RPLND).Patients and MethodsWe identified patients with stage I NSGCTT with initial orchiectomy within the Surveillance, Epidemiology, and End Results (SEER) database (1988-2015). Subsequent surveillance versus CHT versus RPLND use rates were reported. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used after propensity score (PS) matching. These tests first compared surveillance versus AT (CHT vs. RPLND) and subsequently CHT versus RPLND.ResultsOf 5034 patients with stage I NSGCTT, 61.2%, 24.9%, and 13.9%, respectively, underwent surveillance, CHT, and RPLND. Between 1988 and 2015, surveillance (estimated annual percentage change [EAPC]: +1.1%, P < .001) and CHT (EAPC: +2.3%, P < .001) rates increased. RPLND rates decreased (EAPC: ?5.7%; P < .001). After PS matching, CRR models failed to identify AT as an independent predictor of lower mortality relative to surveillance. However, after PS matching, CRR models identified RPLND as an independent predictor of lower CSM (hazard ratio, 0.26; P = .002) relative to CHT. No difference in OCM rates was recorded (hazard ratio, 1.25; P = .2).ConclusionSurveillance and CHT use rates increased while RPLND decreased in the last two decades. Virtually the same outcomes were recorded between surveillance and AT. However, within AT, RPLND was associated with lower CSM than CHT.     

Conditional survival of patients with urothelial carcinoma of the urinary bladder treated with radical cystectomy

Aim of studyTo examine the impact of survival probability according to duration of survivorship following radical cystectomy (RC) in patients diagnosed with urothelial carcinoma of the urinary bladder (UCUB).MethodsOverall, 4991 UCUB patients who underwent RC were abstracted. The cumulative survival estimates were used to generate conditional survival rates. Cox regression analyses were performed for prediction of cancer-specific mortality (CSM), according to duration of survivorship.ResultsThe five-year CSM-free survival rate was 63.9% at RC, and increased to 71.0%, 77.5%, 81.7%, 85.9% and 86.3% in patients who survived ⩾1, 2, 3, 4 and 5 years, respectively. Patients with pT2–4 disease benefitted from the highest increase in survivorship two years after RC. The same findings were recorded according to patients’ nodal status.ConclusionThe survival of the first two years after RC markedly improves individual patient prognosis. The prognostic gains differ according to patient and tumour characteristics.     

Adherence to Guideline Recommendations for Perioperative Chemotherapy in Patients with pN2-3 M0 Squamous Cell Carcinoma of the Penis: Temporal Trends and Survival Outcomes

AimsTo analyse contemporary perioperative chemotherapy (CHT) guideline adherence rates for pN2-3 M0 squamous cell carcinoma of the penis, as well as CHT association with cancer-specific (CSM) and other-cause mortality (OCM).Materials and methodsWithin the Surveillance, Epidemiology, and End Results databases, 311 pN2-3 M0 squamous cell carcinoma of the penis patients treated with inguinal lymph node dissection were identified. Univariable and multivariable logistic regression analyses focused on CHT rates, whereas cumulative incidence plots and multivariable competing risks regression analyses tested for CSM and OCM rates.ResultsCHT was administered to 140 (45%) patients and rates increased from 37.5 to 62.2% (2004–2015; P = 0.02). Specifically, annual CHT rates increased over time in patients younger or equal to 65 years and in patients older than 65 years (44.4–84.6% versus 28.6–50%, respectively), but this trend was not statistically significant (P = 0.1 and P = 0.2, respectively). The median follow-up was 13 months for both CHT (interquartile range 8.0–32.2) and no-CHT subgroups (interquartile range 5.0–40.0). In multivariable logistic regression analyses, more contemporary year of diagnosis interval (odds ratio 2.08, P < 0.01) and age older than 75 years (odds ratio 0.14, P < 0.001) were independent predictors of CHT use. In multivariable competing risks regression analyses, CHT use did not affect CSM (hazard ratio 1.02; P = 0.7) or OCM (hazard ratio 1.56; P = 0.8).ConclusionsCHT adherence rates sharply increased in the most recent years. Despite this increase over time, the lack of efficacy regarding CSM benefit is disappointing.     

Partial Cystectomy With Pelvic Lymph Node Dissection for Patients With Nonmetastatic Stage pT2-T3 Urothelial Carcinoma of Urinary Bladder: Temporal Trends and Survival Outcomes

IntroductionWe investigated the effect of partial cystectomy (PC) on cancer-specific mortality (CSM) and other-cause mortality (OCM) and the effect of pelvic lymph node dissection (PLND) during PC on CSM.Materials and MethodsWithin the Surveillance, Epidemiology, and End Results database (2004-2015), 11,429 cases of nonmetastatic stage pT2-T3 urothelial carcinoma of the urinary bladder treated with either PC or radical cystectomy (RC) were identified. All comparisons between PC and RC relied on propensity score (PS; ratio, 1:1) adjusted univariable and multivariable logistic and competing risks regression models. In contrast, all comparisons between PLND and no PLND at PC relied on inverse probability of treatment weighting-adjusted univariable and multivariable Cox regression models.ResultsWithin the SEER database, PC had been performed in 979 patients (8.6%). The PC annual rates decreased from 11.0% to 6.8% during the study period (P < .001). In PS-adjusted multivariable analyses focusing on CSM and OCM, no statistically significant difference between the PC and RC groups (P = .2 and P = .3, respectively). The annual PLND rates with PC (50.3%) did not vary over time (P = .3). In the overall cohort and the PC subgroup, PLND was associated with a lower CSM rate (hazard ratio, 0.56; P < .001; and hazard ratio, 0.57; P < .001, respectively).ConclusionsA small proportion of patients with stage pT2-T3 urothelial carcinoma of the urinary bladder were candidates for PC. In the PS-adjusted multivariable analyses, no statistically significant differences were found in CSM or OCM between the PC and RC groups. Within the PC group, PLND had been omitted 50% of the time despite its association with lower CSM.     

Effect of Thoracic Radiotherapy Timing and Fractionation on Survival in Nonmetastatic Small Cell Lung Carcinoma

BackgroundThe optimal timing of thoracic radiation therapy (RT) in relation to chemotherapy is unknown in the treatment of nonmetastatic small cell lung cancer (SCLC). We analyzed the National Cancer Data Base (NCDB) to assess the effect on overall survival (OS) of RT timing with chemotherapy for patients with SCLC.Materials and MethodsThe NCDB was queried for patients diagnosed with nonmetastatic SCLC from 1998 to 2011 who had undergone definitive chemoradiation. The patients were stratified into quartiles according to the interval between the start of chemotherapy and the start of RT. The first and second quartiles (RT started 0-20 days after chemotherapy) were classified as “early” RT and the third and fourth quartiles (RT started 21-126 days after chemotherapy) as “late” RT. Patients were included if they had received hyperfractionated 45 Gy in 30 fractions or standard fractionation of ≥ 60 Gy in 1.8- to 2-Gy fractions. Kaplan-Meier analyses of OS were performed, and multivariable Cox regression analysis was conducted to assess the effect of the covariates on OS.ResultsA total of 8391 patients were included (50.5% had received early RT). Early RT was associated with significant improvement in survival (5-year OS, 21.9% vs. 19.1%; P = .01). On subgroup analysis, the survival advantage for early RT was significant for patients receiving hyperfractionated RT (5-year OS, 28.2% vs. 21.2%; P = .004) but not for those receiving standard fractionation (19.8% vs. 18.4%; P = .29). On multivariable Cox regression analysis, hyperfractionated RT was associated with reduced mortality (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.85-0.96; P = .001), but early RT was not (HR, 0.98; 95% CI, 0.94-1.04; P = .53).ConclusionThese data support the early initiation of hyperfractionated thoracic RT for nonmetastatic SCLC.     

EORTC Progression Score Identifies Patients at High Risk of Cancer-Specific Mortality After Radical Cystectomy for Secondary Muscle-Invasive Bladder Cancer

BackgroundThe aim of this study was to develop a risk stratification of patients with muscle-invasive bladder cancer (MIBC) after radical cystectomy (RC). For this purpose, we compared the cancer-specific mortality (CSM) of patients with primary MIBC and patients with secondary MIBC in different risk groups according to the European Organisation for Research and Treatment of Cancer (EORTC) progression score.Patients and MethodsThe records of 521 consecutive patients treated with RC for clinical MIBC according to transurethral resection of bladder cancer (TURBT) diagnosis were reviewed. Of the 521 patients, 399 (76.6%) had primary MIBC (study group 1 [SG1]) and 122 (23.4%) had secondary MIBC (study group 2 [SG2]). Patients in SG2 were stratified into risk groups according to the results of the first and last TURBT in non-MIBC using the EORTC progression score.ResultsCSM for patients with primary and secondary MIBC did not differ significantly. Patients in SG2 with the highest risk for tumor stage progression at time of the first and last TURBT in non-MIBC showed a significantly higher CSM after RC compared with patients with low-to-intermediate risk and compared with patients in SG1. In multivariable analyses, stage pT 3/4 (hazard ratio [HR], 2.12; P < .001), lymphovascular invasion (LVI) (HR, 3.47; P < .001), female sex (HR, 1.35; P = .048), and time from diagnosis of MIBC to RC > 90 days (HR, 2.07; P < .001) were significantly associated with higher CSM.ConclusionRisk stratification by the EORTC progression score can help to identify those patients with the highest risk of CSM after progression to MIBC and thus enable us to offer these patients a multimodal treatment. Our results need to be verified in large prospective studies.     

Radical cystectomy improves survival in patients with stage T1 squamous cell carcinoma and neuroendocrine carcinoma of the urinary bladder

BackgroundRadical cystectomy (RC) is often performed for T1 variant histology bladder cancer (VHBC), based on weak clinical evidence. We tested for cancer specific survival (CSS) differences after RC between T1 VHBC vs. urothelial carcinoma of the urinary bladder (UBC).MethodsWithin the Surveillance, Epidemiology and End Results registry (SEER, 2001–2016), we retrospectively identified T1N0M0 VHBC (adenocarcinoma, squamous cell carcinoma [SqCC], neuroendocrine carcinoma and other VHBC) and UBC patients. Kaplan-Meier plots, multivariate Cox regression models (CRM) with inverse probability treatment weighting (IPTW) and competing risks regression (CRR) tested CSS rates after RC in stage T1 vs. no-RC according to VHBC type and UBC.ResultsOf all 37,528 T1N0M0 bladder cancer patients, 1726 (4.6%) harboured VHBC. Of those, 598 (1.6%) had SqCC, 409 (1.1%) adenocarcinoma, 249 (0.7%) neuroendocrine carcinoma and 470 (1.3%) other VHBC. RC was performed in 7.4–11.0% of VHBC vs. 5.1% of high grade UBC patients. In patients with neuroendocrine and SqCC, RC was associated with higher CSS rates than any other surgical treatment modality (both p ≤ 0.01). Sixty-month CSS was 100% vs. 67% in neuroendocrine and 86% vs. 66% in SqCC in unadjusted analyses and remained statistically significantly higher in multivariate, IPTW adjusted analyses and in multivariate CRR. No difference was recorded for adenocarcinoma or other VHBC types.ConclusionsRC for stage T1N0M0 VHBC appears to provide a protective effect with respect to CSS in patients with SqCC and neuroendocrine carcinoma, but not in adenocarcinoma or other VHBC.     

Evaluation of Cause of Death After Radical Cystectomy for Patients With Bladder Cancer: The Impact of Age at the Time of Surgery

IntroductionPatients with bladder cancer treated with radical cystectomy (RC) have heterogeneous results in term of cancer-specific (CSM) and other cause mortality (OCM). Our aim is to assess the impact of age on cause of death after RC.Patients and MethodsWe retrospectively analyzed the data of 1222 patients treated with RC and bilateral pelvic lymph node dissection owing to nonmetastatic bladder cancer between 1990 and 2013. Patients were stratified according to age (< 59 vs. 60-69 vs. 70-79 vs. ≥ 80 years), tumor T stage at RC (pT0-T2 vs. pT3-T4), and tumor N stage at RC (pN+ vs. pN0). Competing-risks survival analyses were used to estimate CSM and OCM rates.ResultsWith a median follow up of 6 years, 92 (7.5%) and 385 (31.5%) OCM and CSM were recorded. The 5-year CSM and OCM rates were 40% and 8.8%, respectively. After stratification according to disease stage and patient age, CSM emerged as the main cause of mortality in all patient subgroups. The 5-year OCM was 4.6%, 4.8%, 11%, and 32% for patients aged < 60 years versus 60 to 69 years versus 70 to 79 years versus ≥ 80 years, respectively. The 5-years CSM was 34%, 45%, 35%, and 56% for patients aged < 60 years versus 60 to 69 years versus 70 to 79 years versus ≥ 80 years, respectively. Similar findings were observed stratifying the population according to pathologic T and N stage.ConclusionCSM is the preponderant cause of death for all the patients, regardless of age or stage. In this regard, RC also seems to be a reasonable approach for octogenarians.     

Adjuvant radiotherapy improves long-term survival after resection for gallbladder cancer A population-based cohort study

BackgroundData supporting routine use of adjuvant radiotherapy (RT) compared to without RT (noRT) for gallbladder cancer (GBC) is unclear. This study aimed to determine whether RT improves long-term survival following resection for GBC.MethodsPatients receiving resection for GBC followed by RT from 2004 to 2016 were identified from the National Cancer Database (NCDB). Patients with survival <6 months were excluded to account for immortal time bias. Propensity score matching (PSM) and Cox regression was performed to account for selection bias and analyze impact of RT on overall survival.ResultsOf 7514 (77%) noRT and 2261 (23%) RT, 2067 noRT and 2067 RT patients remained after PSM. After matching, RT was associated with improved survival (median: 26.2 vs 21.5 months, p < 0.001), which remained after multivariable adjustment (HR: 0.82, CI_95%: 0.76–0.89, p < 0.001). On multivariable interaction analyses, this benefit persisted irrespective of nodal status: N0 (HR: 0.84, CI_95%: 0.77–0.93), N1 (HR: 0.77, CI_95%: 0.68–0.88), N2/N3 (HR: 0.56, CI_95%: 0.35–0.91), margin status: R0 (HR: 0.85, CI_95%: 0.78–0.93), R1 (HR: 0.78, CI_95%: 0.68–0.88) and use of adjuvant chemotherapy (AC) (HR: 0.67, CI_95%: 0.57–0.79). Benefit with RT were also seen in patients with T2 - T4 disease and in patients undergoing simple and extended cholecystectomy.ConclusionRT following resection was associated with improved survival in this study, even in margin-negative and node-negative disease. These findings may suggest addition of RT into multimodality therapy for GBC.     

Survival Outcomes for Metastatic Prostate Cancer Patients Treated With Radical Prostatectomy or Radiation Therapy: A SEER-based Study

BackgroundPatients with metastatic prostate cancer (mPCa) have a very low 5-year survival rate. How to choose proper treatment of mPCa remains controversial.MethodWithin the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015), we performed analyses of cancer-specific mortality (CSM) and overall mortality (OM) in the comparisons of local treatment (LT) versus no local treatment (NLT) and radical prostatectomy (RP) versus radiation therapy (RT). To balance the characteristics between 2 treatment groups, propensity score matching was performed. Considering the selection bias, we additionally used an instrument variate (IVA) to calculate the unmeasured confounders.ResultMultivariate regression showed that patients receiving LT had the lower risks of OM and CSM after adjustment of covariates (hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.35-0.44 and HR 0.39, 95% CI 0.34-0.45). In the IVA-adjusted model, LT showed more survival benefits compared with NLT, with HR of 0.57 (95% CI 0.50-0.65) and cancer-specific HR of 0.59 (95% CI 0.51-0.68), respectively. For those receiving LT, adjusted multivariate regression indicated that RP is superior to RT (HR 0.60; 95% CI 0.43-0.83 for OM and HR 0.61; 95% CI 0.42-0.91 for CSM). The IVA-adjusted model also showed that RP presented with potentially better survival outcome compared with RT, although the effect was not statistically significant (HR 0.63; 95% CI 0.26-1.54 for OM and HR 0.47; 95% CI 0.16-1.35 for CSM).ConclusionAmong patients with metastatic prostate cancer, LT might bring better survival benefits in decreasing CSM and all-cause mortality compared with NLT. For those receiving LT, RP showed better survival outcomes than RT.