Contemporary survival in metastatic bladder cancer patients: A population-based study.

The overall survival (OS) improvement after the advent of several novel systemic therapies, designed for treatment of metastatic urothelial carcinoma of the urinary bladder (mUCUB), is not conclusively studied in either contemporary UCUB patients and/or non-UCUB patients. Within the Surveillance, Epidemiology, and End Results database, contemporary (2017-2020) and historical (2000-2016) systemic therapy-exposed metastatic UCUB and, subsequently, non-UCUB patients were identified. Separate Kaplan-Meier and multivariable Cox regression (CRM) analyses first addressed OS in mUCUB and, subsequently, in metastatic non-UCUB (mn-UCUB). Of 3443 systemic therapy-exposed patients, 2725 (79%) harbored mUCUB versus 709 (21%) harbored mn-UCUB. Of 2725 mUCUB patients, 582 (21%) were contemporary (2017-2020) versus 2143 (79%) were historical (2000-2016). In mUCUB, median OS was 11 months in contemporary versus 8 months in historical patients (Δ = 3 months; p < .0001). After multivariable CRM, contemporary membership status (2017-2020) independently predicted lower overall mortality (OM; hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.60-0.76; p < .001). Of 709 mn-UCUB patients, 167 (24%) were contemporary (2017-2020) and 542 (76%) were historical (2000-2016). In mn-UCUB, median OS was 8 months in contemporary versus 7 months in historical patients (Δ = 1 month; p = .034). After multivariable CRM, contemporary membership status (2017-2020) was associated with HR of 0.81 (95% CI = 0.66-1.01; p = .06). In conclusion, contemporary systemic therapy-exposed metastatic patients exhibited better OS in UCUB. However, the magnitude of survival benefit was threefold higher in mUCUB and approximated the survival benefits recorded in prospective randomized trials of novel systemic therapies.

Other-cause mortality in incidental prostate cancer.

BACKGROUND: In incidental prostate cancer (IPCa), elevated other-cause mortality (OCM) may obviate the need for active treatment. We tested OCM rates in IPCa according to treatment type and cancer grade and we hypothesized that OCM is significantly higher in not-actively-treated patients. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2015), IPCa patients were identified. Smoothed cumulative incidence plots as well as multivariable competing risks regression models were fitted to address OCM after adjustment for cancer-specific mortality (CSM). RESULTS: Of 5121 IPCa patients, 3655 (71%) were not-actively-treated while 1466 (29%) were actively-treated. Incidental PCa not-actively-treated patients were older and exhibited higher proportion of Gleason sum (GS) 6 and clinical T1a stage. In smoothed cumulative incidence plots, 5-year OCM was 20% for not-actively-treated versus 8% for actively-treated patients. Conversely, 5-year CSM was 5% for not-actively-treated versus 4% for actively-treated patients. No active treatment was associated with 1.4-fold higher OCM, even after adjustment for age, cancer characteristics, and CSM. According to GS, OCM reached 16%, 27%, and 35% in GS 6, 7, and 8-10 not-actively-treated IPCa patients, respectively and exceeded CSM recorded for the same three groups (2%, 6%, and 28%, respectively). CONCLUSION: Our results quantified OCM rates, confirming that in not-actively-treated IPCa patients OCM is indeed significantly higher than in their actively-treated counterparts (HR: 1.4). These observations validate the use of no active treatment in IPCa patients, in whom OCM greatly surpasses CSM (20% vs. 5%).

Adjuvant Systemic Therapy Improved Survival After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

BACKGROUND: The purpose of this study was to test for survival differences according to adjuvant chemotherapy (AC) status in radical nephroureterectomy (RNU) patients with pT2-T4 and/or N1-2 upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (SEER, 2007-2020), patients with UTUC treated with AC versus RNU alone were identified. Kaplan-Meier plots and multivariable Cox regression models addressed cancer-specific mortality (CSM). RESULTS: Of 1995 patients with UTUC, 804 (40%) underwent AC versus 1191 (60%) RNU alone. AC rates increased from 36.1 to 57.0% over time in the overall cohort [estimated annual percentage changes (EAPC) ± 4.5%, p < 0.001]. The increase was from 28.8 to 50.0% in TanyN0 patients (EAPC ± 7.8%, p < 0.001) versus 50.0-70.9% in TanyN1-2 patients (EAPC ± 2.3%, p = 0.002). Within 698 patients harboring TanyN1-2 stage, median CSM was 31 months after AC versus 16 months in RNU alone (Δ = 15 months, p < 0.0001) and AC independently predicted lower CSM [hazard ratio (HR) 0.64; p < 0.001]. Similarly, within subgroup analyses according to stage, relative to RNU alone, AC independently predicted lower CSM in T2N1-2 (HR 0.49; p = 0.04), in T3N1-2 (HR 0.72; p = 0.015), and in T4N1-2 (HR 0.49, p < 0.001) patients. Conversely, in all TanyN0 as well as in all stage-specific subgroup analyses addressing N0 patients, AC did not affect CSM rates (all p > 0.05). CONCLUSIONS: In RNU patients, AC use is associated with significantly lower CSM in lymph-node-positive (N1-2) patients but not in lymph-node-negative patients (N0). The distinction between N1-2 and N0 regarding the effect of AC on CSM applied across all T stages from T2 to T4, inclusively.

Perioperative Complications and In-Hospital Mortality in Partial and Radical Nephrectomy Patients with Heart-Valve Replacement.

BACKGROUND: In-hospital mortality and complication rates after partial and radical nephrectomy in patients with history of heart-valve replacement are unknown. PATIENTS AND METHODS: Relying on the National Inpatient Sample (2000-2019), kidney cancer patients undergoing partial or radical nephrectomy were stratified according to presence or absence of heart-valve replacement. Multivariable logistic and Poisson regression models addressed adverse hospital outcomes. RESULTS: Overall, 39,673 patients underwent partial nephrectomy versus 94,890 radical nephrectomy. Of those, 248 (0.6%) and 676 (0.7%) had a history of heart-valve replacement. Heart-valve replacement patients were older (median partial nephrectomy 69 versus 60 years; radical nephrectomy 71 versus 63 years), and more frequently exhibited Charlson comorbidity index ≥ 3 (partial nephrectomy 22 versus 12%; radical nephrectomy 32 versus 23%). In partial nephrectomy patients, history of heart-valve replacement increased the risk of cardiac complications [odds ratio (OR) 4.33; p < 0.001), blood transfusions (OR 2.00; p < 0.001), intraoperative complications (OR 1.53; p = 0.03), and longer hospital stay [rate ratio (RR) 1.25; p < 0.001], but not in-hospital mortality (p = 0.5). In radical nephrectomy patients, history of heart-valve replacement increased risk of postoperative bleeding (OR 4.13; p < 0.001), cardiac complications (OR 2.72; p < 0.001), intraoperative complications (OR 1.53; p < 0.001), blood transfusions (OR 1.27; p = 0.02), and longer hospital stay (RR 1.12; p < 0.001), but not in-hospital mortality (p = 0.5). CONCLUSIONS: History of heart-valve replacement independently predicted four of twelve adverse outcomes in partial nephrectomy and five of twelve adverse outcomes in radical nephrectomy patients including intraoperative and cardiac complications, blood transfusions, and longer hospital stay. Conversely, no statistically significant differences were observed in in-hospital mortality.

Radiotherapy Versus Partial Penectomy for T1 Squamous Cell Carcinoma of the Penis.

BACKGROUND: Radiotherapy (RT) represents an alternative treatment option for patients with T1 squamous cell carcinoma of the penis (SCCP), with proven feasibility and tolerability. However, it has never been directly compared with partial penectomy (PP) using cancer-specific mortality (CSM) as an end point. METHODS: In the Surveillance, Epidemiology, and End Results database (2000-2020), T1N0M0 SCCP patients treated with RT or PP were identified. This study relied on 1:4 propensity score-matching (PSM) for age at diagnosis, tumor stage, and tumor grade. Subsequently, cumulative incidence plots as well as multivariable competing risks regression (CRR) models addressed CSM. Additionally, the study accounted for the confounding effect of other-cause mortality (OCM). RESULTS: Of 895 patients with T1N0M0 SCCP, 55 (6.1%) underwent RT and 840 (93.9%) underwent PP. The RT and PP patients had a similar age distribution (median age, 70 vs 70 years) and more frequently harbored grade I or II tumors (67.3% vs 75.8%) as well as T1a-stage disease (67.3% vs 74.3%). After 1:4 PSM, 55 (100%) of the 55 RT patients versus 220 (26.2%) of the 840 PP patients were included in the study. The 10-year CSM derived from the cumulative incidence plots was 25.4% for RT and 14.4% for PP. In the multivariable CRR models, RT independently predicted a higher CSM than PP (hazard ratio, 1.99; 95% confidence interval, 1.05-3.80; p = 0.04). CONCLUSION: For the T1N0M0 SCCP patients treated in the community, RT was associated with nearly a twofold higher CSM than PP. Ideally, a validation study based on tertiary care institution data should be conducted to test whether this CSM disadvantage is operational only in the community or not.

Trimodal therapy effect on survival in urothelial vs non-urothelial bladder cancer.

OBJECTIVE: To address cancer-specific mortality free-survival (CSM-FS) differences in patients with urothelial carcinoma of the urinary bladder (UCUB) vs non-UCUB who underwent trimodal therapy (TMT), according to organ confined (OC: T2N0M0) vs non-organ confined (NOC: T3-4NanyM0 or TanyN1-3M0) clinical stages. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4N0-N3M0 bladder cancer treated with TMT, defined as the combination of transurethral resection of bladder tumour, chemotherapy, and radiotherapy. Temporal trends described TMT use over time. Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM in UCUB vs non-UCUB according to OC vs NOC stages. RESULTS: Of 5130 assessable TMT-treated patients, 425 (8%) harboured non-UCUB vs 4705 (92%) who had UCUB. The TMT rates increased for patients with OC UCUB from 92.4% to 96.8% (estimated annual percentage change of 0.4%, P < 0.001), but not in the NOC stages (P = 0.3). In the OC stage, the median CSM-FS was 36 months in patients with non-UCUB vs 60 months in those with UCUB, respectively (P = 0.01). Conversely, in the NOC stage, the median CSM-FS was 23 months both in UCUB and non-UCUB (P = 0.9). In the MCR models addressing OC stage, non-UCUB histology independently predicted higher CSM (hazard ratio 1.45, P = 0.004), but not in the NOC stage (P = 0.9). CONCLUSION: In OC UCUB, TMT rates have increased over time in a guideline-consistent fashion. Patients with OC non-UCUB treated with TMT showed a CSM disadvantage relative to OC UCUB. In the NOC stage, use of TMT resulted in dismal CSM, regardless of UCUB vs non-UCUB histology.

Cancer-specific mortality in non-metastatic T1a renal cell carcinoma treated with radiotherapy versus partial nephrectomy.

PURPOSE: Radiotherapy (RT) represents a treatment option for small renal masses with proven feasibility and tolerability. However, it has never been directly compared to partial nephrectomy (PN) with cancer-specific mortality (CSM) as an endpoint. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified T1aN0M0 renal cell carcinoma (RCC) patients treated with RT or PN. We relied on 1:1 propensity score matching (PSM) for age, tumor size and histology. Subsequently, cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. The same methodology was then re-applied to a subset of patients with tumor size 21-40 mm. RESULTS: Of 40,355 patients with T1aN0M0 RCC, 40,262 underwent PN (99.8%) vs 93 underwent RT (0.2%). RT patients were older (median age 72 vs 60 years, p < 0.001) and harbored larger tumor size (median size 28 vs 25 mm, p < 0.001) and a higher proportion of non-clear cell RCC (49% vs 22%, p < 0.001). After 1:1 PSM (92 RT versus 92 PN patients), cumulative incidence plots' derived CSM was 21.3 vs 4%, respectively. In multivariable CRR models, RT independently predicted higher CSM (hazard ratio (HR) 4.3, p < 0.001). In the subgroup with tumor size 21-40 mm, after 1:1 PSM (72 RT versus 72 PN patients), cumulative incidence plots derived CSM was 21.3% vs 4%, respectively. In multivariable CRR models, RT also independently predicted higher CSM (HR 4.7, p = 0.001). CONCLUSIONS: In T1aN0M0 RCC patients, relative to PN, RT is associated with significantly higher absolute and relative CSM, even in patients with tumor size 21-40 mm.

Contemporary conditional cancer-specific survival rates in surgically treated nonmetastatic primary urethral carcinoma.

BACKGROUND: We examined the effect of disease-free interval (DFI) duration on cancer-specific mortality (CSM)-free survival, otherwise known as the effect of conditional survival, in radical urethrectomy nonmetastatic primary urethral carcinoma (PUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, patient (age, sex, race/ethnicity, and marital status) and tumor (stage and histology) characteristics, as well as systemic therapy exposure status of nonmetastatic PUC patients were tabulated. Conditional survival estimates at 5-year were assessed based on DFI duration and according to stage at presentation (T1 -2N0 vs. T3-4N0-2). RESULTS: Of all 512 radical urethrectomy PUC patients, 278 (54%) harbored T1-2N0 stage versus 234 (46%) harbored T3-4N0-2 stage. In 512 PUC patients, 5-year CSM-free survival at initial diagnosis was 61.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 85.6%. In 278 T1-2N0 PUC patients, 5-year CSM-free survival at initial diagnosis was 68.4%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 86.9%. In 234 T3-4N0-2 PUC patients, 5-year CSM-free survival at initial diagnosis was 53.8%. Provided a DFI duration of 36 months, 5-year CSM-free survival was 83.6%. CONCLUSIONS: Although intuitively, clinicians and patients are well aware of the concept that increasing DFI duration improves survival probability, only a few clinicians can accurately estimate the magnitude of survival improvement, as was done within the current study. Such information is crucial to survivors, especially in those diagnosed with rare malignancies, where the survival estimation according to DFI duration is even more challenging.

The effect of married status on cancer-specific mortality in nonmetastatic pelvic liposarcoma patients according to sex.

BACKGROUND: In nonmetastatic pelvic liposarcoma patients, it is unknown whether married status is associated with better cancer-control outcome defined as cancer-specific mortality (CSM). We addressed this knowledge gap and hypothesized that married status is associated with lower CSM rates in both male and female patients. METHODS: Within the Surveillance, Epidemiology, and End Results database (2000-2020), nonmetastatic pelvic liposarcoma patients were identified. Kaplan-Meier plots and univariable and multivariable Cox regression models (CRMs) predicting CSM according to marital status were used in the overall cohort and in male and female subgroups. RESULTS: Of 1078 liposarcoma patients, 764 (71%) were male and 314 (29%) female. Of 764 male patients, 542 (71%) were married. Conversely, of 314 female patients, 192 (61%) were married. In the overall cohort, 5-year cancer-specific mortality-free survival (CSM-FS) rates were 89% for married versus 83% for unmarried patients (Δ = 6%). In multivariable CRMs, married status did not independently predict lower CSM (hazard ratio [HR]: 0.74, p = 0.06). In males, 5-year CSM-FS rates were 89% for married versus 86% for unmarried patients (Δ = 3%). In multivariable CRMs, married status did not independently predict lower CSM (HR: 0.85, p = 0.4). In females, 5-year CSM-FS rates were 88% for married versus 79% for unmarried patients (Δ = 9%). In multivariable CRMs, married status independently predicted lower CSM (HR: 0.58, p = 0.03). CONCLUSIONS: In nonmetastatic pelvic liposarcoma patients, married status independently predicted lower CSM only in female patients. In consequence, unmarried female patients should ideally require more assistance and more frequent follow-up than their married counterparts.

Contemporary seminal vesicle invasion rates in NCCN high-risk prostate cancer patients.

BACKGROUND: Contemporary seminal vesicle invasion (SVI) rates in National Cancer Comprehensive Network (NCCN) high-risk prostate cancer (PCa) patients are not well known but essential for treatment planning. We examined SVI rates according to individual patient characteristics for purpose of treatment planning. MATERIALS AND METHODS: Within Surveillance, Epidemiology, and End Results (SEER) database (2010-2015), 4975 NCCN high-risk patients were identified. In the development cohort (SEER geographic region of residence: South, North-East, Mid-West, n = 2456), we fitted a multivariable logistic regression model predicting SVI. Its accuracy, calibration, and decision curve analyses (DCAs) were then tested versus previous models within the external validation cohort (SEER geographic region of residence: West, n = 2519). RESULTS: Out of 4975 patients, 28% had SVI. SVI rate ranged from 8% to 89% according to clinical T stage, prostate-specific antigen (PSA), biopsy Gleason Grade Group and percentage of positive biopsy cores. In the development cohort, these variables were independent predictors of SVI. In the external validation cohort, the current model achieved 77.6% accuracy vs 73.7% for Memorial Sloan Kettering Cancer Centre (MSKCC) vs 68.6% for Gallina et al. Calibration was better than for the two alternatives: departures from ideal predictions were 6.0% for the current model vs 9.8% for MSKCC vs 38.5% for Gallina et al. In DCAs, the current model outperformed both alternatives. Finally, different nomogram cutoffs allowed to discriminate between low versus high SVI risk patients. CONCLUSIONS: More than a quarter of NCCN high-risk PCa patients harbored SVI. Since SVI positivity rate varies from 8% to 89%, the currently developed model offers a valuable approach to distinguish between low and high SVI risk patients.

Use of inpatient palliative care in metastatic urethral cancer.

BACKGROUND: In metastatic urethral cancer, temporal trends, and patterns of inpatient palliative care (IPC) use are unknown. METHODS: Relying on the National Inpatient Sample (2006-2019), metastatic urethral cancer patients were stratified according to IPC use. Estimated annual percentage changes (EAPC) analyses and multivariable logistic regression models (LRM) for the prediction of IPC use were fitted. RESULTS: Of 1,106 metastatic urethral cancer patients, 199 (18%) received IPC. IPC use increased from 5.8 to 28.0% over time in the overall cohort (EAPC +9.8%; P < 0.001), from <12.5 to 35.1% (EAPC +11.2%; P < 0.001), and from <12.5 to 24.7% (EAPC +9.4%; P = 0.01) in respectively females and males. Lowest IPC rates were recorded in the Midwest (13.5%) vs. highest in the South (22.5%). IPC patients were more frequently female (44 vs. 37%), and more frequently exhibited bone metastases (45 vs. 34%). In multivariable LRM, female sex (multivariable odds ratio [OR] 1.46, 95% confidence interval [CI] 1.05-2.02; P = 0.02), and bone metastases (OR 1.46, 95%CI 1.02-2.10; P = 0.04) independently predicted higher IPC rates. Conversely, hospitalization in the Midwest (OR 0.53, 95%CI 0.31-0.91; P = 0.02), and in the Northeast (OR 0.48, 95%CI 0.28-0.82; P = 0.01) were both associated with lower IPC use than hospitalization in the West. CONCLUSION: IPC use in metastatic urethral cancer increased from a marginal rate of 5.8% to as high as 28%. Ideally, differences according to sex, metastatic site, and region should be addressed to improve IPC use rates.

Married Status Affects Rates of Treatment and Mortality in Male and Female Renal Cell Carcinoma Patients Across all Stages.

INTRODUCTION: The association between treatment rates and cancer specific mortality (CSM) according to married status in male and female clear cell renal cell carcinoma (ccRCC) patients across all stages is unknown. PATIENT AND METHODS: Using the Surveillance, Epidemiology, and End Results database (2004-2020), ccRCC patients were stratified according to married status (married vs. unmarried). Logistic regression models addressed treatment rates; Cox regression models addressed CSM rates. RESULTS: Of 98,142 patients, 43,999 (72%) males and 20,287 (55%) females were married. In stage-specific analyses, married status independently predicted higher nephrectomy rates in males and females (all P ≤ .03). In stage IV, married status predicted higher systemic therapy rate in males (P < .001), but not in females. In survival analyses, married males exhibited lower CSM rates relative to unmarried males (all P ≤ .02). Conversely, married females exhibited lower CSM rates only in stages I and III (all P ≤ .02), but not in stages II and IV. In subgroup analyses of T1aN0M0 patients, married status was associated with higher partial nephrectomy rates in both males and females (all P ≤ .005). CONCLUSION: In ccRCC, married status invariably predicts higher rates of guideline recommended surgical management (nephrectomy and partial nephrectomy). Moreover, even after adjustment for treatment type, married status independently predicted lower CSM rates in males across all stages. However, the effect of married status in females is only operational in stages I and III. Lack of association between married status in stages II and IV may potentially be explained by stronger association with treatment assignment which reduces the residual effect on survival.

The effect of race/ethnicity on cancer-specific mortality after trimodal therapy.

INTRODUCTION: Trimodal therapy (TMT) is the most validated bladder-sparing treatment for organ-confined urothelial carcinoma of the urinary bladder (OC UCUB, namely cT2N0M0). However, it is unknown if barriers to the use of TMT or cancer-specific mortality (CSM) differences exist according to race/ethnicity. We addressed this knowledge gap. MATERIAL AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified OC UCUB patients aged from 18 to 85 treated with radical cystectomy (RC) or TMT. Temporal trends described TMT versus RC use over time. Subsequently, in the subgroup of TMT-treated patients, survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM according to race/ethnicity. RESULTS: Among 19,501 assessable patients, 15,336 (79%) underwent RC versus 4165 TMT (21%). Overall, of all races/ethnicities, 16,245 (83.3%) were White Americans, 1215 (6.3%) Hispanics, 1160 (5.9%) African Americans, and 881 (4.5%) Asian/Pacific Islanders. Among TMT-treated patients, 3460 (83.1%) were White Americans, 298 (7.1%) African Americans, 218 (5.3%) Hispanics, and 189 (4.5%) Asian/Pacific Islanders. The lowest rate of TMT use relative to RC and TMT patients was recorded in Hispanics (17.9%). Over time, TMT use increased in White Americans (EAPC: + 4.5%, p = 0.001) and Asians/Pacific Islanders (EAPC: + 5.2%, p = 0.003), but not in others. Kaplan-Meier analyses showed median CSM of 49 months, 41 months, and 34 months and not reached in White Americans, Hispanics, African Americans, and Asian/Pacific Islanders, respectively (p = 0.02). In MCR models, two race/ethnicity subgroups independently predicted either worse (African Americans, HR: 1.20, p = 0.02) or better CSM (Asian/Pacific Islanders, HR: 0.75, p = 0.02). CONCLUSION: Race/ethnicity affects both access to TMT (lower access in Hispanics) as well as survival after TMT (better in Asians/Pacific Islanders and worse in African Americans).

Non-Surgical Bladder-Sparing Multimodal Management in Organ-Confined Urothelial Carcinoma of the Urinary Bladder: A Population-Based Analysis.

BACKGROUND: Trimodal therapy is considered the most validated bladder-sparing treatment in patients with organ-confined urothelial carcinoma of the urinary bladder (T2N0M0). However, scarce evidence exists regarding cancer-specific mortality (CSM) differences between trimodal therapy and other non-extirpative multimodal treatment options such as radiotherapy alone after transurethral resection (TURBT + RT) or chemotherapy alone after transurethral resection (TURBT + CT). METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified T2N0M0 patients treated with either trimodal therapy, TURBT + CT, or TURBT + RT. Temporal trends described trimodal therapy vs. TUBRT + CT vs. TURBT + RT use over time. Survival analyses consisting of Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM according to each treatment modality. RESULTS: 3729 (40%) patients underwent TMT vs. 4030 (43%) TURBT + CT vs. 1599 (17%) TURBT + RT. Over time, trimodal therapy use (Estimating annual percent change, EAPC: +1.2%, p = 0.01) and TURBT + CT use increased (EAPC: +1.5%, p = 0.01). In MCR models, relative to trimodal therapy, TURBT + CT exhibited 1-14-fold higher CSM and TURBT + RT 1.68-fold higher CSM. In a subgroup analysis, TURBT + RT was associated with 1.42-fold higher CSM than TURBT + CT (p < 0.001). CONCLUSIONS: Strict trimodal therapy that includes both CT and RT after TURBT offers the best cancer control. When strict trimodal therapy cannot be delivered, cancer-specific survival outcomes appear to be superior with TURBT + chemotherapy compared to TURBT + RT.

Neoadjuvant Versus Adjuvant Chemotherapy in Non-Metastatic Locally-Advanced Stage Radical Cystectomy Candidates.

INTRODUCTION: Administration of chemotherapy before radical cystectomy (RC) in neoadjuvant setting (NAC) or after RC in adjuvant setting (ADJ) are both associated with a survival benefit relative to RC alone. However, no study directly compared the magnitude of such benefit associated with NAC versus ADJ in locally-advanced UCUB patients (T3-T4N0M0). We addressed this knowledge gap. METHODS: Within the Surveillance, Epidemiology, and End Results database (2007-2020), we identified T3-T4N0M0 UCUB patients who underwent NAC+RC or RC+ADJ. Cumulative incidence plots and multivariable competing risks regression (CRR) models were fitted. The same methodology was then re-applied in T3 and then T4 patient subgroups. RESULTS: Of 875 assessable patients, 603 harbored T3 stage (69.0%) and 272 harbored T4 stage (31.0%). Of all 875, 563 (64.0%) underwent RC+ADJ versus 312 (36.0%) NAC+RC. NAC+RC rates increased over time (EAPC=+6.1%, P = .001). Cumulative incidence plots derived five-year CSM rates were 40.3% in NAC+RC versus 36.1% in RC+ADJ patients (P = .2). In multivariable CRR models that also adjusted for OCM, no statistically significant difference in CSM was recorded when NAC+RC was compared to RC+ADJ (HR:0.85, P = .1). Virtually the same observations were made in subgroup analyses where CSM associated with NAC+RC was not different from that recorded in RC+ADJ (HR: 0.89 and P = .4 in T3 stage and HR:0.8 and P = .2 in T4 stage). CONCLUSION: In locally-advanced UCUB, NAC rates have sharply increased over time. However, the approach based on neoadjuvant chemotherapy prior to RC have not resulted in a statistically significant CSM benefit relative to RC+ADJ.

Incidence, Characteristics and Survival Rates of Bladder Cancer after Rectosigmoid Cancer Radiation.

BACKGROUND: Historical external beam radiation therapy (EBRT) for rectosigmoid cancer (RCa) predisposed patients to an increased risk of secondary bladder cancer (BCa). However, no contemporary radiotherapy studies are available. We addressed this knowledge gap. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2000-2020), we identified non-metastatic RCa patients who either underwent radiotherapy (EBRT+) or did not (EBRT-). Cumulative incidence plots and multivariable competing risk regression models (CRR) were fitted to address rates of BCa after RCa. In the subgroup of BCa patients, the same methodology addressed BCa-specific mortality (BCSM) according to EBRT exposure status. RESULTS: Of the 188,658 non-metastatic RCa patients, 54,562 (29%) were EBRT+ vs. 134,096 (73%) who were EBRT-. In the cumulative incidence plots, the ten-year BCa rates were 0.7% in EBRT+ vs. 0.7% in EBRT- patients (p = 0.8). In the CRR, EBRT+ status was unrelated to BCa rates (multivariable HR: 1.1, p = 0.8). In the subgroup of 1416 patients with BCa after RCa, 443 (31%) were EBRT+ vs. 973 (69%) who were EBRT-. In the cumulative incidence plots, the ten-year BCSM rates were 10.6% in EBRT+ vs. 12.1% in EBRT- patients (p = 0.7). In the CRR, EBRT+ status was unrelated to subsequent BCSM rates (multivariable HR: 0.9, p = 0.9). CONCLUSION: Although historical EBRT for RCa predisposed patients to higher BCa rates, contemporary EBRT for RCa is not associated with increased subsequent BCa risk. Moreover, in patients with BCa after RCa, exposure to EBRT does not affect BCSM.

Survival of Metastatic Urothelial Carcinoma of Urinary Bladder According to Number and Location of Visceral Metastases.

OBJECTIVE: To test the association between number as well as locations of organ-specific metastatic sites and overall survival (OS) in systhemic-therapy exposed metastatic urothelial carcinoma of urinary bladder (mUCUB) patients. METHODS: Within Surveillance, Epidemiology and End Results database (2010-2020), all systhemic therapy-exposed mUCUB patients were identified. Kaplan-Meier and multivariable Cox regression (CRM) models first addressed OS in patients according to number of metastatic organ-locations: solitary versus 2 versus 3 or more. Subsequently, separate analyses stratified according to location type were completed in patients with solitary metastatic organ-location as well as in patients with 2 metastatic organ-locations. RESULTS: Of 1,310 mUCUB, 1,069 (82%) harbored solitary metastatic organ-location versus 193 (15%) harbored 2 separate metastatic organ-locations versus 48 (3%) harbored 3 or more metastatic organ-locations. Median OS decreased with increasing number of metastatic organ-locations (solitary vs. 2 vs. 3 or more, P < .0001). In multivariable CRM, relative to solitary metastatic organ-location, 2 (HR: 1.57, 95 Confidence interval [CI], 1.33-1.85) as well as 3 or more (HR: 1.69, 95% CI, 1.23-2.31) metastatic organ-locations independently predicted higher overall mortality (OM) (P = .001). In patients with solitary metastatic organ-location, brain metastases independently predicted higher OM (HR 1.67; 95% CI, 1.05-2.67; P = .03) than other locations. In patients with 2 metastatic organ-locations, no differences in OM were recorded according to organ type location. CONCLUSION: In systemic therapy exposed mUCUB, number of metastatic organ-locations (solitary vs. 2 vs. 3 or more), independently predicted increasingly worse prognosis. In patients with solitary metastatic organ-location, brain purported worse prognosis than others.

Perioperative complications and in-hospital mortality in radical cystectomy patients with heart-valve replacement.

PURPOSE: To assess in-hospital mortality and complication rates after radical cystectomy (RC) in patients with history of heart-valve replacement. MATERIALS AND METHODS: Using the National Inpatient Sample (2000-2019), non-metastatic bladder cancer patients undergoing RC were stratified according to history of heart-valve replacement. Regression models (RM) predicted hospital outcomes. RESULTS: Of 25,535 RC patients, 250 (1.0%) harbored history of heart-valve replacement. Heart-valve replacement patients were older (median 74 vs. 70 years), more frequently male (87.2 vs. 80.6%), and more frequently had Charlson comorbidity index ≥3 (26.8 vs. 18.9%). In RC patients with history of heart-valve replacement vs. others, 62 vs. 2634 (24.8 vs. 10.4%) experienced cardiac complications, 28 vs. 3092 (11.2 vs. 12.2%) intraoperative complications, 11 vs. 1046 (4.4 vs. 4.1%) infections, <11 vs. 594 (<4.4 vs. 2.3%) perioperative bleeding, <11 vs. 699 (<4.4 vs. 2.8%) vascular complications, 74 vs. 6225 (29.6 vs. 24.7%) received blood transfusions, 37 vs. 3054 (14.8 vs. 12.1%) critical care therapy (CCT), and in-hospital mortality was recorded in <11 vs. 463 (<4.4 vs. 1.8%) patients. In multivariable RM, history of heart-valve replacement independently predicted cardiac complications (odds ratio 2.20, 95% confidence interval 1.62-2.99; p < 0.001). Conversely, no statically significant association was recorded between history of heart-valve replacement and length of stay, estimated hospital cost, intraoperative complications, perioperative bleeding, vascular complications, infections, blood transfusions, CCT use, and in-hospital mortality. CONCLUSIONS: Radical cystectomy patients with history of heart-valve replacement exhibited a 2.2-fold higher risk of cardiac complications, but no other complications, including no significantly higher in-hospital mortality.

Rare histological prostate cancer subtypes: Cancer-specific and other-cause mortality.

BACKGROUND: To assess cancer-specific mortality (CSM) and other-cause mortality (OCM) rates in patients with rare histological prostate cancer subtypes. METHODS: Using the Surveillance, Epidemiology, and End Results database (2004-2020), we applied smoothed cumulative incidence plots and competing risks regression (CRR) models. RESULTS: Of 827,549 patients, 1510 (0.18%) harbored ductal, 952 (0.12%) neuroendocrine, 462 (0.06%) mucinous, and 95 (0.01%) signet ring cell carcinoma. In the localized stage, five-year CSM vs. OCM rates ranged from 2 vs. 10% in acinar and 3 vs. 8% in mucinous, to 55 vs. 19% in neuroendocrine carcinoma patients. In the locally advanced stage, five-year CSM vs. OCM rates ranged from 5 vs. 6% in acinar, to 14 vs. 16% in ductal, and to 71 vs. 15% in neuroendocrine carcinoma patients. In the metastatic stage, five-year CSM vs. OCM rates ranged from 49 vs. 15% in signet ring cell and 56 vs. 16% in mucinous, to 63 vs. 9% in ductal and 85 vs. 12% in neuroendocrine carcinoma. In multivariable CRR, localized neuroendocrine (HR 3.09), locally advanced neuroendocrine (HR 9.66), locally advanced ductal (HR 2.26), and finally metastatic neuroendocrine carcinoma patients (HR 3.57; all p < 0.001) exhibited higher CSM rates relative to acinar adenocarcinoma patients. CONCLUSIONS: Compared to acinar adenocarcinoma, patients with neuroendocrine carcinoma of all stages and locally advanced ductal carcinoma exhibit higher CSM rates. Conversely, CSM rates of mucinous and signet ring cell adenocarcinoma do not differ from those of acinar adenocarcinoma.