Sarcomatoid Dedifferentiation as a Predictor of Cancer-Specific Mortality in Surgically Treated Localized Renal Cell Carcinoma.

BACKGROUND: In contemporary surgically treated patients with localized high-grade (G3 or G4) clear-cell renal cell carcinoma (ccRCC), it is not known whether presence of sarcomatoid dedifferentiation is an independent predictor and/or an effect modifier, when cancer-specific mortality (CSM) represents an endpoint. METHODS: Within the Surveillance, Epidemiology, and End Results database, all surgically treated localized high-grade ccRCC patients treated between 2010 and 2020 were identified. Univariable and multivariable Cox-regression models were used. RESULTS: In 18,853 surgically treated localized high-grade (G3 or G4) ccRCC patients, 5-year CSM-free survival was 87% (62% vs. 88% with vs. without sarcomatoid dedifferentiation, p < 0.001). Presence of sarcomatoid dedifferentiation was an independent predictor of higher CSM (hazard ratio [HR] 1.8, p < 0.001). In univariable survival analyses predicting CSM, presence versus absence of sarcomatoid dedifferentiation in G3 versus G4 yielded the following hazard ratios: HR 1.0 in absent sarcomatoid dedifferentiation in G3; HR 2.7 (p < 0.001) in absent sarcomatoid dedifferentiation in G4; HR 3.9 (p < 0.001) in present sarcomatoid dedifferentiation in G3; HR 5.1 (p < 0.001) in present sarcomatoid dedifferentiation in G4. Finally, in multivariable Cox-regression analyses, the interaction terms defining present versus absent sarcomatoid dedifferentiation in G3 versus G4 represented independent predictors of higher CSM. CONCLUSIONS: In contemporary surgically treated patients with localized high-grade ccRCC, sarcomatoid dedifferentiation is not only an independent multivariable predictor of higher CSM, but also interacts with tumor grade and results in even better ability to predict CSM.

Survival benefit of nephroureterectomy in systemic therapy exposed metastatic upper tract urinary urothelial carcinoma patients.

BACKGROUND: It is unknown whether the stage of the primary may influence the survival (OS) of metastatic upper tract urothelial carcinoma (mUTUC) patients treated with nephroureterectomy (NU) and systemic therapy (ST). We tested this hypothesis within a large-scale North American cohort. METHODS: Within Surveillance Epidemiology and End Results database 2000-2020, all mUTUC patients treated with ST+NU or with ST alone were identified. Kaplan-Maier plots depicted OS. Multivariable Cox regression (MCR) models tested for differences between ST+NU and ST alone predicting overall mortality (OM). All analyses were performed in localized (T1-T2) and then repeated in locally advanced (T3-T4) patients. RESULTS: Of all 728 mUTUC patients, 187 (26%) harbored T1-T2 vs 541 (74%) harbored T3-T4. In T1-T2 patients, the median OS was 20 months in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU independently predicted lower OM (HR 0.37, p < 0.001). Conversely, in T3-T4 patients, the median OS was 12 in ST+NU vs 10 months in ST alone. Moreover, in MCR analyses that also relied on 3 months' landmark analyses, the combination of ST+NU was not independently associated with lower OM (HR 0.85, p = 0.1). CONCLUSIONS: In mUTUC patients, treated with ST, NU drastically improved survival in T1-T2 patients, even after strict methodological adjustments (multivariable and landmark analyses). However, this survival benefit did not apply to patients with locally more advanced disease (T3-T4).

Unmarried Status Effect on Stage at Presentation and Treatment Patterns in Non-Metastatic Upper Tract Urothelial Carcinoma Patients.

BACKGROUND: Unmarried status has been associated with higher proportions of locally advanced stage and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused on the association between unmarried status and advanced stage (T3-4N0-2) at presentation and lower nephroureterectomy (RNU) and systemic therapy (ST) rates in non-metastatic upper tract urothelial carcinoma (UTUC) patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020, all non-metastatic UTUC patients were identified. Multivariable logistic regression models (LRMs) tested for differences in stage at presentation and treatment (RNU and ST) according to marital status (married vs unmarried), in a sex-specific fashion. RESULTS: Of all 8544 non-metastatic UTUC patients, 4748 (56%) were male vs 3190 (44%) were female. Of all 4748 male UTUC patients, 1191 (25%) were unmarried. Of all 3190 female UTUC patients, 1608 (50%) were unmarried. In multivariable LRMs predicting RNU, unmarried status was an independent predictor of lower RNU rates in male (Odds Ratio [OR]: 0.56; P < .001), but not in female (OR: 0.81; P = .1) non-metastatic UTUC patients. In multivariable LRMs predicting ST exposure, unmarried status was an independent predictor of lower ST rates in both male (OR:0.73; P = .03) and female (OR:0.64; P < .001) UTUC patients. In multivariable LRMs predicting locally advanced stage (T3-4N0-2), unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male (OR: 0.95; P = .5) or female (OR: 0.99; P = .9) UTUC patients. CONCLUSIONS: Unmarried male UTUC patients appear at risk of less being able to access RNU, relative to their married counterparts. Moreover, unmarried UTUC patients appear to less benefit from ST, regardless of sex. Conversely, unmarried status was not associated with an increased risk of locally advanced stage at presentation in either male or female UTUC patients.

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.

Prognostic significance of lymph node count in surgically treated patients with T2-4 stage nonmetastatic adrenocortical carcinoma.

PURPOSE: The role of lymphadenectomy and the optimal lymph node count (LNC) cut-off in nonmetastatic adrenocortical carcinoma (nmACC) are unclear. METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database, surgically treated nmACC patients with T2-4 stages were identified between 2004 and 2020. We tested for cancer-specific mortality (CSM) differences according to pathological N-stage (pN0 vs. pN1) and two previously recommended LNC cut-offs (≥4 vs. ≥5) were tested in pN0 and subsequently in pN1 subgroups in Kaplan-Meier plots and multivariable Cox regression models. RESULTS: Of 710 surgically treated nmACC patients, 185 (26%) underwent lymphadenectomy and were assessable for further analyses based on available LNC data. Of 185 assessable patients, 152 (82%) were pN0 and 33 (18%) were pN1. In Kaplan-Meier analyses, CSM-free survival was 74 vs. 14 months (Δ 60 months, P ≤ 0.001) in pN0 vs. pN1 patients, respectively. In multivariable analyses, pN1 was an independent predictor of higher CSM (HR:3.13, P < 0.001). In sensitivity analyses addressing pN0, LNC cut-off of ≥4 was associated with lower CSM (multivariable hazard ratio [HR]: 0.52; P = 0.002). In sensitivity analyses addressing pN0, no difference was recorded when a LNC cut-off of ≥5 was used (HR:0.60, P = 0.09). In pN1 patients, neither of the cut-offs (≥4 and ≥5) resulted in a statistically significant stratification of CSM rate, and neither reached independent predictor status (all P > 0.05). CONCLUSIONS: Lymphadenectomy provides a prognostic benefit in nmACC patients and identifies pN1 patients with dismal prognosis. Conversely, in pN0 patients, a LNC cut-off ≥4 identifies those with particularly favorable prognosis.

Surgically treated pelvic liposarcoma and leiomyosarcoma: The effect of tumor size on cancer-specific survival.

INTRODUCTION: In soft tissue pelvic liposarcoma and leiomyosarcoma, it is unknown whether a specific tumor size cut-off may help to better predict prognosis, defined as cancer-specific survival (CSS). We tested whether different tumor size cut-offs, could improve CSS prediction. MATERIALS AND METHODS: Surgically treated non-metastatic soft tissue pelvic sarcoma patients were identified (Surveillance, Epidemiology, and End Results 2004-2019). Kaplan-Meier plots, univariable and multivariable Cox-regression models and receiver operating characteristic-derived area under the curve (AUC) estimates were used. RESULTS: Overall, 672 (65 %) liposarcoma (median tumor size 11 cm, interquartile range [IQR] 7-16) and 367 (35 %) leiomyosarcoma (median tumor size 8 cm, IQR 5-12) patients were identified. The p-value derived ideal tumor size cut-off was 17.1 cm, in liposarcoma and 7.0 cm, in leiomyosarcoma. In liposarcoma, according to p-value derived cut-off, five-year CSS rates were 92 vs 83 % (≤17.1 vs > 17.1 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 83.8 to 86.8 % (Δ = 3 %). Similarly, among previously established cut-offs (5 vs 10 vs 15 cm), also 15 cm represented an independent predictor of CSS and improved prognostic ability from 83.8 to 87.0 % (Δ = 3.2 %). In leiomyosarcoma, according to p-value derived cut-off, five-year CSS rates were 86 vs 55 % (≤7.0 vs > 7.0 cm). This cut-off represented an independent predictor of CSS and improved prognostic ability from 68.6 to 76.5 % (Δ = 7.9 %). CONCLUSIONS: In liposarcoma, the p-value derived tumor size cut-off was 17.1 cm vs 7.0 cm, in leiomyosarcoma. In both histologic subtypes, these cut-offs exhibited the optimal statistical characteristics (univariable, multivariable and AUC analyses). In liposarcoma, the 15 cm cut-off represented a valuable alternative.

Contemporary validation of cT1a vs. cT1b substaging of incidental prostate cancer.

OBJECTIVE: The cT1a vs. cT1b substratification was introduced in 1992 but never formally tested since. We tested the discriminative ability of cT1a vs. cT1b substaging on cancer-specific survival (CSS) in contemporary incidental prostate cancer (PCa) patients. DESIGN, SETTING AND PARTICIPANTS: Incidental (cT1a/cT1b) PCa patients were identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier estimates, as well as uni- and multivariable Cox regression models predicted CSS at five years. Subgroup analyses addressed CSS at five years according to active vs. no local treatment (NLT) as well as Gleason score sum (GS; 6 vs. 7 vs. ≥ 8). RESULTS AND LIMITATION: We identified a total of 5,155 incidental prostate cancer patients of which 3,035 (59%) were stage cT1a vs. 2,120 (41%) were stage cT1b. In all incidental PCa patients, CSS at five years was 95% (95% CI 0.94-0.96). In cT1a patients, CSS at five years was 98 vs. 90% in cT1b patients (p < 0.001). In multivariable Cox regression analyses, cT1b independently predicted 2.8-fold higher CSM than cT1a (HR 2.5, 95% CI 1.8-3.6, p < 0.001) for incidental PCa patients who underwent NLT. In subgroup analyses, cT1b represented an independent predictor of higher CSM in GS ≥ 8 (HR 3.0, 95% CI 1.4-6.2, p = 0.003), and GS 7 (HR 3.9, 95% CI 1.6-9.7 p = 0.002) patients who underwent NLT. For actively treated patients, cT1b was not independently associated with worse CSM. CONCLUSION: The historical subclassification of cT1a vs. cT1b in incidental PCa patients displayed a strong ability to discriminate CSS in contemporary GS 7 and GS ≥ 8 patients who underwent NLT. However, no statistically significant difference was recorded in actively treated patients. In consequence, the importance of the current substage stratification predominantly applies to GS ≥ 8 patients who undergo a non-active treatment approach.

Surveillance of non-muscle-invasive bladder cancer with blue-light cystoscopy: a meta-analysis.

OBJECTIVE: To compare the value of flexible blue-light cystoscopy (BLC) vs flexible white-light cystoscopy (WLC) in the surveillance setting of non-muscle-invasive bladder cancer (NMIBC). METHODS: All major databases were searched for articles published before May 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The primary outcome was the accuracy of flexible BLC vs WLC in detecting bladder cancer recurrence among suspicious bladder lesions. RESULTS: A total of 10 articles, comprising 1634 patients, were deemed eligible for the quantitative synthesis. In the meta-analysis focusing on the detection of disease recurrence, there was no difference between flexible BLC and WLC (odds ratio [OR] 1.08, 95% confidence interval [CI] 0.82-1.41)]; the risk difference (RD) showed 1% of flexible BLC, corresponding to a number needed to treat (NNT) of 100. In the subgroup meta-analysis of detection of carcinoma in situ (CIS) only, there was again no significant difference between flexible BLC and WLC (OR 1.19, 95% CI 0.82-1.69), BLC was associated with a RD of 2% (NNT = 50). The positive predictive values for flexible BLC and WLC in detecting all types of recurrence were 72% and 66%, respectively, and for CIS they were 39% and 29%, respectively. CONCLUSION: Surveillance of NMIBC with flexible BLC could detect more suspicious lesions and consequently more tumour recurrences compared to flexible WLC, with a increase in the rate of false positives leading to overtreatment. A total of 100 and 50 flexible BLC procedures would need to be performed to find on additional tumor and CIS recurences, respectively. A risk-stratified strategy for patient selection could be considered when using flexible BLC for the surveillance of NMIBC patients.

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.

Identifying low cancer-specific mortality risk lymph node-positive radical prostatectomy patients.

OBJECTIVES: To identify low cancer-specific mortality (CSM) risk lymph node-positive (pN1) radical prostatectomy (RP) patients. METHODS: Within Surveillance, Epidemiology and End Results database (2010-2015) pN1 RP patients were identified. Kaplan-Meier plots and multivariable Cox-regression (MCR) models were used. Pathological characteristics were used to identify patients at lowest CSM risk. RESULTS: Overall, 2197 pN1 RP patients were identified. Overall, 5-year cancer-specific survival (CSS) rate was 93.3%. In MCR models ISUP GG1-2 (hazard ratio [HR]: 0.12, p < 0.001), GG3 (HR: 0.14, p < 0.001), GG4 (HR: 0.35, p = 0.002), pT2 (HR: 0.27, p = 0.012), pT3a (HR: 0.28, p = 0.003), pT3b (HR: 0.39, p = 0.009), and 1-2 positive lymph nodes (HR: 0.64, p = 0.04) independently predicted lower CSM. Pathological characteristics subgroups with the most protective hazard ratios were used to identify low-risk (ISUP GG1-3 and pT2-3a and 1-2 positive lymph nodes) patients versus others (ISUP GG4-5 or pT3b-4 or ≥3 positive lymph nodes). In Kaplan-Meier analyses, 5-year CSS rates were 99.3% for low-risk (n = 480, 21.8%) versus 91.8% (p < 0.001) for others (n = 1717, 78.2%). CONCLUSIONS: Lymph node-positive RP patients exhibit variable CSS rates. Within this heterogeneous group, those at very low risk of CSM may be identified based on pathological characteristics, namely ISUP GG1-3, pT2-3a, and 1-2 positive lymph nodes. Such stratification scheme might be of value for individual patients counseling, as well as in design of clinical trials.

Unmarried status effect on stage at presentation and treatment patterns in primary urethral carcinoma patients.

BACKGROUND: Unmarried status has been associated with advanced stage at presentation and lower treatment dose intensification rates in several urological and non-urological malignancies. However, no previous investigators focused of the association of unmarried status with locally advanced stage (T3-4N0-2) at presentation and lower bi-/trimodal therapy rates in primary urethral carcinoma (PUC) patients. To address these knowledge gaps, we relied on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Within the SEER database 2000 to 2020, all non-metastatic PUC patients were identified. Logistic regression models (LRMs) tested for differences in stage at presentation and treatment modality in the overall cohort and then in a sex-specific fashion, according to marital status (married vs unmarried). RESULTS: Of all 1,430 non-metastatic PUC patients, 1,004 (70%) were male vs 426 (30%) were female. Of 1,004 male PUC patients, 272 (27%) were unmarried. Of all 426 female PUC patients, 239 (56%) were unmarried. In multivariable LRMs predicting T3-4N0-2, unmarried status was independently associated with an increased risk of locally advanced stage at presentation in the overall cohort (odds ratio [OR]:1.31; P = 0.03) and in female patients (OR:1.62; P = 0.02), but not in male PUC patients (P = 0.6). In multivariable LRMs predicting bi-/trimodal therapy, unmarried status was an independent predictor of lower bi-/trimodal therapy rates in the overall cohort (OR:0.73; P = 0.02) and in male patients (OR:0.60; P = 0.007), but not in female PUC patients (P = 0.6). CONCLUSIONS: Unmarried female PUC patients more likely harbored locally advanced stage at presentation. Conversely, unmarried male PUC patients are less likely to benefit from bi-/trimodal therapy.

Regional differences in upper tract urothelial carcinoma patients across the United States.

BACKGROUND: It is unknown whether regional differences in patient, tumor, and treatment characteristics of upper tract urothelial carcinoma (UTUC) patients exist and may potentially result in regional overall mortality (OM) differences. We tested for inter-regional differences, according to Surveillance, Epidemiology, and End Results (SEER) registries. METHODS: Using SEER database 2000 to 2016, patient (age, sex, race/ethnicity), tumor (location, grade) and treatment (nephroureterectomy, systemic therapy [ST]) characteristics of UTUC patients of all-stages were tabulated and graphically depicted in a stage-specific fashion (T1-2N0M0 vs. T3-4N0M0 vs. TanyN1-2M0/TanyNanyM1). Multivariable Cox regression (MCR) models tested for inter-regional differences in OM. RESULTS: Regarding T1-2N0M0 patients, statistically significant differences existed for race/ethnicity (Caucasian 71 vs. 98%), location (renal pelvis: 55 vs. 67%), grade (high 60 vs. 83%) and ST (5.5 vs. 13.9%). In MCR models, registries 3 (Hazard ratio [HR]:1.39; P < 0.001) and 4 (HR:1.31; P = 0.01) independently predicted higher OM and Registry 8 (HR:0.64; P = 0.001) lower OM. Regarding T3-4N0M0 patients, statistically significant differences existed for race/ethnicity (Caucasian 70 vs. 98%), location (renal pelvis: 67 vs. 76%), grade (high 84 vs. 94%) and ST (18.7 vs. 29.5%). In MCR models, registries 3 (HR:1.42; P < 0.001) and 4 (HR:1.31; P = 0.009) independently predicted higher OM. Regarding TanyN1-2M0/TanyNanyM1 patients, statistically significant differences existed for location (renal pelvis: 63 vs. 82%), grade (high 92 vs. 98%) and ST (53.4 vs. 58.8%). In MCR models, Registry 3 (HR:1.37; P = 0.004) independently predicted higher OM and Registry 2, (HR:0.78; P = 0.02) lower OM. CONCLUSIONS: Inter-regional differences were recorded in patients, tumor, and treatment characteristics. Even after adjustment for these characteristics, OM differences persisted which may be indicative of regional differences in quality of care or expertise in UTUC management.

Multivariable model versus AJCC staging system: cancer-specific survival predictions in adrenocortical carcinoma.

We developed a novel contemporary population-based model for predicting cancer-specific survival (CSS) in adrenocortical carcinoma (ACC) patients and compared it with the established 8th edition of the American Joint Committee on Cancer staging system (AJCC). Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified 1056 ACC patients. Univariable Cox regression model addressed CSS. Harrell's concordance index (C-index) quantified accuracy after 2000 bootstrap resamples for internal validation. The multivariable Cox regression model included the most informative, statistically significant predictors. Calibration and decision curve analyses (DCAs) tested the multivariable model as well as AJCC in head-to-head comparisons. Age at diagnosis (>60 vs ≤60 years), surgery, T, N, and M stages were included in the multivariable model. Multivariable model C-index for 3-year CSS prediction was 0.795 vs 0.757 for AJCC. Multivariable model outperformed AJCC in DCAs for the majority of possible CSS-predicted values. Both models exhibited similar calibration properties. Finally, the range of the multivariable model CSS predicted probabilities raged 0.02-75.3% versus only four single AJCC values, specifically 73.2% for stage I, 69.7% for stage II, 46.6% for stage III, and 15.5% for stage IV. The greatest benefit of the multivariable model-generated CSS probabilities applied to AJCC stage I and II patients. The multivariable model was more accurate than AJCC staging when CSS predictions represented the endpoint. Additionally, the multivariable model outperformed AJCC in DCAs. Finally, the AJCC appeared to lag behind the multivariable model when discrimination addressed AJCC stage I and II patients.

Survival differences in non-seminoma testis cancer patients according to race/ethnicity.

BACKGROUND: Historic evidence suggests that non-Caucasian race/ethnicity predisposes to higher testis cancer-specific mortality (CSM) in non-seminoma. However, it is unknown, whether higher CSM in non-Caucasians applies to Hispanics or Asians or African-Americans, or all of the above groups. In contemporary patients, we tested whether CSM is higher in these select non-Caucasian groups than in Caucasians, in overall and in stage-specific comparisons: stage I vs. stage II vs. stage III. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (2004 -2019) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of race/ethnicity on CSM after stratification for stage (I vs. II vs. III) and adjustment for prognosis groups in stage III. RESULTS: In all 13,515 non-seminoma patients, CSM in non-Caucasians was invariably higher than in Caucasians. In stage-specific analyses, race/ethnicity represented an independent predictor of CSM in Hispanics in stage I (HR 1.8, p = 0.004), stage II (HR 2.2, p = 0.007) and stage III (HR 1.4, p < 0.001); in African-Americans in stage I (HR 3.2; p = 0.007) and stage III (HR 1.5; p = 0.042); and in Asians in only stage III (HR 1.6, p = 0.01). CONCLUSIONS: In general, CSM is higher in non-Caucasian non-seminoma patients. However, the CSM increase differs according to non-Caucasian race/ethnicity groups. Specifically, higher CSM applies to all stages of non-seminoma in Hispanics, to stages I and III in African-Americans and only to stage III in Asians. These differences are important for individual patient management, as well as for design of prospective trials.

The Effect of Treatment Intensification on Other-Cause Mortality in Clear-Cell Metastatic Renal Cell Carcinoma Patients.

BACKGROUND: The effect of treatment intensification (systemic therapy [ST] + cytoreductive nephrectomy (CN) vs. ST alone) is unknown regarding rates of other-cause mortality (OCM) in clear-cell metastatic renal cell carcinoma (ccmRCC). We hypothesized that intensified treatment (ST + CN) may result in higher OCM, than when ST is used alone. METHODS: Within the Surveillance, Epidemiology, and End Results database, all ccmRCC patients treated 2010-2018 either with ST + CN or ST alone were identified. Propensity score matching (PSM), cumulative incidence plots, multivariable competing risks regression analyses and 6 months' landmark analyses addressed OCM and cancer-specific mortality (CSM) according to treatment status. RESULTS: Of 2271 ccmRCC patients, 1233 (54%) were treated with ST + CN vs 1038 (46%) with ST alone. After 1:1 PSM, OCM was 5.3 vs. 4.6 % (P = .5) and CSM was 73.4 vs. 88.4% (P < .001) in ST + CN vs. ST alone patients. In multivariable competing risks regression, the combination of ST and CN was not associated with higher OCM (HR 1.3; 95% CI 0.8-2.1; P = .4), vs. ST alone. However, the combination of ST and CN was independently associated with lower CSM (HR 0.5; 95% CI 0.5-0.6; P < .001), vs. ST alone. After 6 months' landmark analyses, these multivariable associations remained unchanged. CONCLUSIONS: The current study indicates no OCM-disadvantage in ST + CN ccmRCC patients, relative to their ST alone counterparts. Conversely, a strong association with lower CSM was recorded in ST + CN patients, relative to their ST alone counterparts. These associations are robust and remained unchanged after strictest statistical adjustment including control for immortal time bias.

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.

Differences in other-cause mortality in metastatic renal cell carcinoma according to partial vs. radical nephrectomy and age: A propensity score matched study.

INTRODUCTION: It is unknown whether the benefit from partial nephrectomy regarding lower other-cause mortality is applicable to older patients with metastatic renal cell carcinoma. MATERIALS AND METHODS: Using Surveillance Epidemiology and End Results database, patients with metastatic renal cell carcinoma, undergoing partial or radical nephrectomy, were stratified according to age (<60, 60-69, and ≥70 years). After propensity score matching, Kaplan-Meier survival analyses and multivariable Cox regression models were used. RESULTS: Of 2,390 patients with metastatic renal cell carcinoma, 885 (37%) were aged <60 years, and 90 (10%) underwent partial nephrectomy; 824 (34%) were aged 60-69 years, and 61 (7%) underwent partial nephrectomy; and 681 (29%) were aged ≥70 years, and 64 (9%) underwent partial nephrectomy. After propensity score matching, in patients aged <60 years, partial nephrectomy was associated with lower other-cause mortality (hazard ratio 0.22; p = 0.02); in patients aged 60-69 years, partial nephrectomy was associated with lower other-cause mortality (hazard ratio 0.38; p = 0.03); but not in patients aged ≥70 years. DISCUSSION: In metastatic renal cell carcinoma, partial nephrectomy is associated with lower other-cause mortality in patients aged <60 years and in patients aged 60-69 years, but not in patients aged ≥70 years. In consequence, consideration of partial nephrectomy might be of great value in younger metastatic renal cell carcinoma patients.

A population-based validation of the IGCCCG Update Consortium for survival in metastatic non-seminoma testis cancer.

BACKGROUND: In 2021, the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium reported improved overall survival (OS) rates in a modern cohort of metastatic non-seminoma testis cancer patients within each of the IGCCCG prognosis groups (96% in good vs. 89% in intermediate vs. 67% in poor), compared to the previous IGCCCG publication (92% in good vs. 80% in intermediate vs. 48% in poor). We hypothesized that a similar survival improvement may apply to a contemporary North-American population-based cohort of non-seminoma testis cancer patients. PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (2010-2018) was used. Kaplan-Meier plots and multivariable Cox regression models tested the effect of IGCCCG prognosis groups on overall mortality (OM). RESULTS: Of 1672 surgically treated metastatic non-seminoma patients, 778 (47%) exhibited good vs. 251 (15%) intermediate vs. 643 (38%) poor prognosis. In the overall cohort, five-year OS rate was 94% for good prognosis vs. 87% for intermediate prognosis vs. 65% for poor prognosis. In multivariable Cox regression models predicting OM, intermediate (Hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.4-3.9, P < 0.001) and poor prognosis group (HR 6.6, 95% CI 1.0-1.0, P < 0.001) were independent predictors of higher OM, relative to good prognosis group. CONCLUSIONS: The survival improvement reported by the IGCCCG Update Consortium is also operational in non-seminoma testis cancer patients within the most contemporary SEER database. This observation indicates that the survival improvement is not only applicable to centres of excellence, but also applies to other institutions at large.

Patient reported outcomes of intermittent self-dilatation after direct vision internal urethrotomy.

PURPOSE: Long-term results on quality of life (QoL) as well as clinical outcomes of intermittent self-dilatation (ISD) of the urethra after direct visual internal urethrotomy (DVIU) are scarce. The aim of this study was to prospectively evaluate patient reported outcomes (PROs) on voiding symptoms and QoL in a large cohort of urethral stricture patients performing ISD. METHODS: We identified a total of 121 patients who performed ISD following DVIU between 2008 and 2013. Baseline assessment was conducted for each patient before ISD was started. Follow-up visits were scheduled in 6-month intervals. Each assessment included the following questionnaires: International prostate symptom score (IPSS), IPSS quality of life index (IPSS-QoL), patient global impression of severity (PGI-S), and patient global impression of improvement (PGI-I). Additional parameters were maximum urinary flow rate (Qmax ), postvoid residual urine, rate of complications, and stricture recurrence. Linear mixed models were used to examine the change over the course of the follow-up visits to the baseline. RESULTS: The median age of the patients was 58 years (interquartile range [IQR]: 43-70). The median follow-up was 17 months (IQR: 7-30). Mean change from baseline IPSS was -6.1, -5.9, -4.2, and -4.8 points at 6, 24, 36, and 48 months. Mean change from baseline IPSS-QoL was -1.3, -1.4, -1.6, and -1.8 points, respectively. Mean PGI-I was 1.7 points at 6, 1.9 points at 24, 1.9 points at 36, and 2.2 points at 48 months after ISD initiation. Mean change of Qmax ranged from 1.7 at 6 to 2.2 mL/s at 48 months. The median complication rate was 3.3% per 6-month ISD interval. Overall, 11 patients developed stricture recurrence (9%). CONCLUSION: ISD after DVIU had no negative impact on patients' QoL (IPSS-QoL, PGI-I, PGI-S). Urodynamic parameters remained stable for up to 48 months with low complications and an acceptable stricture recurrence rate.