Bladder cancer stage and mortality: urban vs. rural residency.

OBJECTIVE: Relative to urban populations, rural patients may have more limited access to care, which may undermine timely bladder cancer (BCa) diagnosis and even survival. METHODS: We tested the effect of residency status (rural areas [RA < 2500 inhabitants] vs. urban clusters [UC ≥ 2500 inhabitants] vs. urbanized areas [UA, ≥50,000 inhabitants]) on BCa stage at presentation, as well as on cancer-specific mortality (CSM) and other cause mortality (OCM), according to the US Census Bureau definition. Multivariate competing risks regression (CRR) models were fitted after matching of RA or UC with UA in stage-stratified analyses. RESULTS: Of 222,330 patients, 3496 (1.6%) resided in RA, 25,462 (11.5%) in UC and 193,372 (87%) in UA. Age, tumor stage, radical cystectomy rates or chemotherapy use were comparable between RA, UC and UA (all p > 0.05). At 10 years, RA was associated with highest OCM followed by UC and UA (30.9% vs. 27.7% vs. 25.6%, p < 0.01). Similarly, CSM was also marginally higher in RA or UC vs. UA (20.0% vs. 20.1% vs. 18.8%, p = 0.01). In stage-stratified, fully matched CRR analyses, increased OCM and CSM only applied to stage T1 BCa patients. CONCLUSION: We did not observe meaningful differences in access to treatment or stage distribution, according to residency status. However, RA and to a lesser extent UC residency status, were associated with higher OCM and marginally higher CSM in T1N0M0 patients. This observation should be further validated or refuted in additional epidemiological investigations.

PSA, stage, grade and prostate cancer specific mortality in Asian American patients relative to Caucasians according to the United States Census Bureau race definitions.

BACKGROUND: The United States Census Bureau recommends distinguishing between "Asians" vs. "Native Hawaiians or Other Pacific Islanders" (NHOPI). We tested for prognostic differences according to this stratification in patients with prostate cancer (PCa) of all stages. METHODS: Descriptive statistics, time-trend analyses, Kaplan-Meier plots and multivariate Cox regression models were used to test for differences at diagnosis, as well as for cancer specific mortality (CSM) according to the Census Bureau's definition in either non-metastatic or metastatic patients vs. 1:4 propensity score (PS)-matched Caucasian controls, identified within the Surveillance, Epidemiology and End Results database (2004-2016). RESULTS: Of all 380,705 PCa patients, NHOPI accounted for 1877 (0.5%) vs. 23,343 (6.1%) remaining Asians vs. 93.4% Caucasians. NHOPI invariably harbored worse PCa characteristics at diagnosis. The rates of PSA ≥ 20 ng/ml, Gleason ≥ 8, T3/T4, N1- and M1 stages were highest for NHOPI, followed by Asians, followed by Caucasians (PSA ≥ 20: 18.4 vs. 14.8 vs. 10.2%, Gleason ≥ 8: 24.9 vs. 22.1, vs. 15.9%, T3/T4: 5.5 vs. 4.2 vs. 3.5%, N1: 4.4 vs. 2.8, vs. 2.7%, M1: 8.3 vs. 4.9 vs. 3.9%). Despite the worst PCa characteristics at diagnosis, NHOPI did not exhibit worse CSM than Caucasians. Moreover, despite worse PCa characteristics, Asians exhibited more favorable CSM than Caucasians in comparisons that focussed on non-metastatic and on metastatic patients. CONCLUSIONS: Our observations corroborate the validity of the distinction between NHOPI and Asian patients according to the Census Bureau's recommendation, since these two groups show differences in PSA, grade and stage characteristics at diagnosis in addition to exhibiting differences in CSM even after PS matching and multivariate adjustment.

Tumor Size Predicts Muscle-invasive and Non-organ-confined Disease in Upper Tract Urothelial Carcinoma at Radical Nephroureterectomy.

BACKGROUND: Pathological stage and grade of renal pelvis urothelial carcinoma (RPUC) are difficult to estimate before radical nephroureterectomy (RNU). OBJECTIVE: To examine tumor size as an independent predictor of muscle-invasive and/or non-organ-confined rates of RPUC at RNU. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results (SEER) database (2004-2016), we identified nonmetastatic RPUC at RNU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: First, we examined stage and grade distributions. Second, two separate univariable and subsequent multivariable logistic regression models (LRMs) were fitted to test the association between tumor size and the rate of (1) muscle-invasive or higher (pT2-4N0-2) and (2) non-organ-confined (pT3-4N0-2) RPUC at RNU. RESULTS AND LIMITATIONS: Of 4657 patients, 3052 (65.5%) had pT2-4N0-2 and 2382 (51.2%) pT3-4N0-2 RPUC at RNU. The median tumor size was 3.7 cm (interquartile range 2.5-5.0). The high-grade RPUC rate ranged from 71.1% to 87.2% (p < 0.001) among SEER registries. Conversely, no differences were recorded for stage (p > 0.05) or tumor size (p = 0.1) across all registries. Rates of pT2-4N0-2 and pT3-4N0-2 RPUC increased with tumor size. Specifically, for tumor size intervals from 0.1-1.0 cm to 9.1-10.0 cm, the pT2-4N0-2 rate ranged from 45% to 83% and the pT3-4N0-2 rate ranged from 23% to 75%, respectively (both p < 0.001). In multivariable LRMs, tumor size (in 1-cm units) was an independent predictor of pT2-4N0-2 (odds ratio [OR] 1.25; p < 0.001) and pT3-4N0-2 (OR 1.30; p < 0.001) disease at RNU. CONCLUSIONS: Tumor size is a key predictor of muscle-invasive or non-organ-confined RPUC. Greater tumor size directly and virtually linearly predicts a higher rate of invasive or non-organ-confined RPUC at RNU. PATIENT SUMMARY: For patients with cancer in urinary tract cells lining the kidney, larger tumor size predicts worse stage of the disease at surgery.

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

OBJECTIVE: To 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. METHODS: Within the Surveillance, Epidemiology and End Results Registry (SEER, 2004-2016), we identified non-metastatic stage T1-2 or T3-4 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. RESULTS: Of 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 T1-2 or T3-4 VHBC patients. Conversely, PLND extent was associated with lower CSM in T1-2, as well as in T3-4 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 T3-4 VHBC (Odds ratio [OR] 1.01, P = .001), stage T1-2 UCUB (OR 1.01, P < .001) and T3-4 UCUB (OR 1.01, P < .001), but not in stage T1-2 VHBC (OR 1.01, P = .3). CONCLUSION: PLND 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.

Upper Urinary Tract Tumors: Variant Histology Versus Urothelial Carcinoma.

PURPOSE: To evaluate stage at presentation and cancer-specific mortality (CSM) in upper urinary tract tumors according to histologic subtype. METHODS: Within the Surveillance, Epidemiology, and End Results registry (SEER, 2004-2016), we identified patients with upper urinary tract tumors with pure variant histology (UTVH) and pure upper urinary tract urothelial carcinoma (UTUC). Cumulative incidence plots, after propensity score matching for tumor and patient characteristics, addressed CSM. Subgroup analyses addressed efficacy of radical nephroureterectomy (RNU) in stage T1-2 and of chemotherapy in metastatic UTVH patients. RESULTS: Of all 11,809 upper urinary tract tumor patients, 154 (1.3%) harbored squamous cell carcinoma (SCC), 86 (0.7%) adenocarcinoma, 39 (0.3%) neuroendocrine carcinoma, 38 (0.3%) other UTVH, and 11,492 (97.3%) UTUC. UTVH patients were more likely to exhibit metastatic stage disease at diagnosis than UTUC (odds ratio, 1.9; 95% confidence interval, 1.3-2.8; P < .01). After detailed matching for performance status, only SCC showed significantly higher CSM than UTUC (multivariate HR = 1.71; P < .01). Subgroup analyses in stage T1-2 RNU patients showed, relative to UTUC patients, no CSM differences for SCC or adenocarcinoma patients. No significant survival benefit for chemotherapy administration was identified in patients with metastatic SCC or metastatic adenocarcinoma. This study is limited by its sample size and the missing centralized pathologic review. CONCLUSIONS: Disease stage at diagnosis is more advanced in UTVH patients than UTUC. Across all stages, CSM is higher for SCC than for UTUC. However, in T1-2 stage disease, RNU results in similar survival in SCC or adenocarcinoma versus UTUC.

Incidence and Survival Rates of Contemporary Patients with Invasive Upper Tract Urothelial Carcinoma.

BACKGROUND: Contemporary incidence and mortality rates of upper tract urothelial carcinoma (UTUC) are unavailable. OBJECTIVE: To describe contemporary UTUC incidence and mortality rates in the USA. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results (SEER) database (2004-2016), we identified 13 075 UTUC patients. Of all, 9208 (70.4%) harbored nonmetastatic UTUC and were treated with radical nephroureterectomy versus 1174 (9.0%) who harbored metastatic UTUC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Age-standardized incidence rates per 100 000 person years were calculated. Kaplan-Meier curves and multivariable Cox regression models addressed cancer-specific and overall mortality. RESULTS AND LIMITATIONS: Overall UTUC age-standardized incidence rates decreased from 1.3 to 1.1 cases per 100 000 person years (average annual percentage change: -1.32%, p = 0.002). Moreover, age-standardized incidence rates decreased for T1-2N0M0 (average annual percentage change: -2.77%, p < 0.001) but increased for T1-4N0-2M1 stage (average annual percentage change: +2.87%, p < 0.01). In nonmetastatic UTUC treated with radical nephroureterectomy, stage, grade, age, and sex (p < 0.001) were independent predictors in multivariable Cox regression models focusing on cancer-specific mortality. In metastatic UTUC, chemotherapy administration, radical nephroureterectomy treatment, and ureteral primary were independent predictors of lower overall mortality in multivariable Cox regression models. CONCLUSIONS: Although overall incidence of UTUC decreased, the incidence of metastatic UTUC increased over the study period. The majority of nonmetastatic UTUC harbored T1N0M0 stage. However, T3N0M0, T4N0M0, and T1-4N1-2M0 stages, respectively, affected 28.9%, 4.6%, and 10.0% of all incident cases. In metastatic UTUC, both chemotherapy and radical nephroureterectomy use exerted an important protective effect on overall mortality, and ureteral primaries exhibited more favorable survival. PATIENT SUMMARY: From 2004 to 2016, the incidence of upper tract urothelial carcinoma decreased in the USA. However, more advanced stages are on the rise.

Micropapillary Versus Urothelial Carcinoma of the Urinary Bladder: Stage at Presentation and Efficacy of Chemotherapy Across All Stages-A SEER-based Study.

BACKGROUND: Stage-specific guideline recommendations are lacking for chemotherapy in micropapillary carcinoma of the urinary bladder (MCUB). OBJECTIVE: To test the efficacy of stage-specific chemotherapy for MCUB. DESIGN, SETTING, AND PARTICIPANTS: Within the Surveillance, Epidemiology and End Results (SEER) registry (2001-2016), we identified patients with MCUB and pure urothelial carcinoma of the urinary bladder (UCUB) of all stages. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier survival analyses and multivariate Cox regression models were used to determine cancer-specific mortality (CSM) in addition to power analyses. RESULTS AND LIMITATIONS: Of 210 491 patients of all stages, 518 (0.2%) harboured MCUB versus 209 973 (99.8%) UCUB. Stage at presentation was invariably higher in MCUB than in UCUB patients. Of the MCUB patients, 223 (43.1%) received chemotherapy versus 42 921 (20.4%) of the UCUB patients. In MCUB patients, chemotherapy improved CSM-free survival significantly in metastatic stage (hazard ratio [HR] 0.36, p = 0.04). Longer median CSM-free survival was also associated with chemotherapy use in addition to radical cystectomy (RC) versus RC alone in non-organ-confined MCUB (HR 0.69, p = 0.2). Additional power analyses revealed an underpowered comparison. Finally, no CSM difference was recorded in organ-confined MCUB according to the use of chemotherapy in addition to RC versus RC alone (HR 0.98, p = 1). CONCLUSIONS: Stage at presentation was invariably higher in MCUB than in UCUB patients. Very important CSM reduction was associated with chemotherapy use in metastatic MCUB. A promising protective effect of perioperative chemotherapy might also be applicable to non-organ-confined MCUB, but without sufficient statistical power. Conversely, no association was recorded in organ-confined MCUB. PATIENT SUMMARY: Patients with micropapillary carcinoma of the urinary bladder (MCUB) present in higher tumour stages than those with urothelial carcinoma of the urinary bladder. Chemotherapy for MCUB is effective in metastatic stages, but of no beneficial effect in organ-confined stage. In not-yet-metastatic but already non-organ-confined stages, we did not have enough observations to show a statistically significant protective effect of chemotherapy.

Radical Cystectomy vs. Multimodality Treatment in T2N0M0 Bladder Cancer: A Population-based, Age-matched Analysis.

BACKGROUND: Controversy still exists regarding efficacy of multimodality treatment (MMT) vs. radical cystectomy (RC) for urothelial carcinoma of the urinary bladder (UCUB). METHODS: Within the SEER database (2004-2016), we retrospectively identified patients with stage T2N0M0 UCUB. Competing risks regression (CRR) tested cancer-specific mortality (CSM) and adjusted for other-cause mortality after MMT vs. RC. Exact matching for age was applied. Subgroup analyses focused on differences in chemotherapy or lymph node dissection rates. In sensitivity analyses, we accounted for 40% understaging rate in patients who underwent MMT. RESULTS: Of 9862 patients with T2N0M0 UCUB, 2675 (27.1%) underwent MMT vs. 5751 (58.3%) RC vs. 1436 (14.6%) radiotherapy (RT) without chemotherapy. MMT rate increased (annually +3.0%, P < .01) and MMT patient age was significantly higher (median 77 years) than RC patient age (68 years). In exact age-matched analyses, 10-year CSM rates were 44.3% vs. 25.9% for MMT vs. RC (multivariate hazard ratio [HR] 0.48); 44.1% vs. 22.8% for MMT vs. RC with chemotherapy (HR 0.43); 40.5% vs. 31.1% for MMT vs. RC without lymph node dissection (HR 0.66), and 55.6% vs. 27.3% for RT without chemotherapy vs. RC (HR 0.37, all P < .001). Sensitivity analyses that addressed understaging of patients who underwent MMT resulted in virtually the same CSM rates. CONCLUSION: In patents with T2N0M0, MMT or even more so RT alone may be associated with higher CSM than RC, even in exact age-matched multivariate CRR analyses, which adjust for other-cause mortality. In consequence, patients with T2 UCUB should be informed of this possible CSM disadvantage outside of highly specialized centers.

Obesity is associated with adverse short-term perioperative outcomes in patients treated with open and robot-assisted radical cystectomy for bladder cancer.

BACKGROUND: Obese patients may be predisposed to adverse perioperative outcomes and it is uncertain whether robot-assisted radical cystectomy (RARC) benefits obese patients in comparison to open radical cystectomy (ORC). Thus, we tested the effect of obesity and surgical approach on perioperative outcomes and total hospital charges. METHODS: Within the National Inpatient Sample database (2008-2015), we identified obese (body mass index ≥30 kg/m2) vs. non-obese patients with non-metastatic bladder cancer treated with RARC or ORC. Estimated annual percent changes and weighted multivariable logistic and linear regression models adjusted for clustering as well as age, comorbidities, hospital volume, and respectively surgical approach, lengths of stay, and/or complications were used. RESULTS: Of all 11,594 patients (unweighted patient count), 1,119 (9.7%) were obese vs. 10,475 (90.3%) were not-obese. Obesity rate increased significantly over time (5.5%-13.3%, annual change: 11%, P = 0.001). RARC, as well as treatment in high volume hospitals was more prevalent in obese vs. non-obese patients (18.3 vs. 14.5% and 40.9 vs. 37.0%, both P < 0.01). In multivariable regression models, obesity independently predicted overall complications (odds ratio [OR] 1.23, confidence interval [CI]: 1.09-1.42), major complications (OR 1.63, CI: 1.41-1.87), longer hospital stay (OR 1.17, CI: 1.02-1.34) and higher total hospital charges ($+8,260, CI: 3951-12,570), all P < 0.01). In subgroup analyses in obese patients, RARC was not associated with overall (OR 1.15, P = 0.4) and major complications (OR 1.10, P = 0.6) or length of stay (OR 0.78, P = 0.1) compared with ORC but with higher hospital charges (+$16,794, P = 0.005). CONCLUSION: Obesity predisposes to higher rates of adverse perioperative outcomes at radical cystectomy. The benefit of RARC could not be validated in obese patients.