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Background: Data regarding North-American incidental (cT1a/b) prostate cancer (PCa) patients is scarce. To address this, incidental PCa characteristics (age, PSA values at diagnosis, Gleason score [GS]), subsequent treatment and cancer-specific survival (CSS) rates were explored., Methods: Incidental PCa patients were identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). Descriptive statistics, annual percentage changes (EAPC), Kaplan-Meier estimates, as well as Cox regression models were used. Bootstrapping technique was used to generate 95% confidence intervals for CSS at 6 years., Results: Of all 344,031 newly diagnosed non metastatic PCa patients, 5155 harbored incidental PCa. Annual rates of incidental PCa increased from 1.9% (2004) to 2.5 % (2015; p = 0.02). PSA values at diagnosis were 0-4 ng/ml in 48% vs. 4-10 ng/ml in 31% vs. > 10 ng/ml in 21%. Of all incidental PCa patients, 64% harbored GS 6 vs. 25% GS 7 vs. 11% GS ≥ 8. Of all incidental PCa patients, 47% were aged < 70, 35% were between 70 and 79 and 18% were ≥ 80 years. Subsequently, 71% underwent no local treatment (NLT) vs. 16% radical prostatectomy (RP) vs. 14% radiotherapy (RT). Proportions of patients with NLT increased from 65 to 81% (p = 0.0001) over the study period (2004-2015). CSS at six years ranged from 58% in GS ≥ 8 patients with NLT to 100% in patients who harbored GS 6 and underwent either RP or RT., Conclusion: Incidental PCa in the United States is rare. Most incidental PCa patients are diagnosed in men aged less than 80 years of age. The majority of incidental PCa patients undergo NLT and enjoy excellent CSS., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objective: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes., Material and Methods: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP., Results: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01)., Conclusion: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA., (© 2023. The Author(s).)

Background: The role of primary tumor ablation (pTA) in metastatic renal cell carcinoma (mRCC) is unknown. We compared pTA-treated mRCC patients to patients who underwent no local treatment (NLT), as well as patients who underwent cytoreductive nephrectomy (CN)., Methods: Within the Surveillance, Epidemiology, and End Results database (SEER, 2004-2020), we identified mRCC patients who underwent either pTA, NLT or CN. Endpoints consisted of overall survival (OM) and other-cause mortality (OCM). Propensity score 1:1 matching (PSM), multivariable cox regression models (OM), as well as, multivariable competing risk regressions (CRR) models (OCM) were used., Results: We identified 27,087 mRCC patients, of whom 82 (0.3%) underwent pTA, 17,266 (64%) NLT and 9,739 (36%) CN. In comparisons of pTA vs. NLT mRCC patients addressing OM, after 1:1 PSM, median survival was 19 months for pTA vs. 4 months for NLT patients (multivariable HR 0.3, 95% CI 0.22-0.47, P < 0.001). No statistically significant OCM differences were recorded in multivariable CRR (HR 1.13 95%, CI 0.52-2.44, P = 0.8). In comparisons of pTA vs. CN, after 1:1 PSM, no statistically significant differences in OM (HR 1.22, 95% CI 0.81-1.83, P = 0.32), as well as OCM (HR 1.4, 95% CI 0.56-3.48, P = 0.5) were recorded., Conclusion: In mRCC patients, pTA is associated with significantly lower mortality compared to NLT. Interestingly, OM rates between pTA and CN mRCC patients do not exhibit statistically significant differences. This preliminary report may suggest that pTA may provide a comparable survival benefit to CN in highly selected mRCC patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To test the ability of the 2015 modified version of the European Network for the Study of Adrenal Tumors staging system (mENSAT) in predicting cancer-specific mortality (CSM), as well as overall mortality (OM) in adrenocortical carcinoma (ACC) patients of all stages, in a large-scale, and contemporary United States cohort., Methods: We relied on the Surveillance, Epidemiology, and End Results (SEER) database (2004-2020) to test the accuracy and calibration of the mENSAT and subsequently compared it to the 8th edition of the American Joint Committee on Cancer staging system (AJCC)., Results: In 858 ACC patients, mENSAT accuracy was 74.7% for 3-year CSM predictions and 73.8% for 3-year OM predictions. The maximum departures from ideal predictions in mENSAT were +17.2% for CSM and +11.8% for OM. Conversely, AJCC accuracy was 74.5% for 3-year CSM predictions and 73.5% for 3-year OM predictions. The maximum departures from ideal predictions in AJCC were -6.7% for CSM and -7.1% for OM., Conclusion: The accuracy of mENSAT is virtually the same as that of AJCC in predicting CSM (74.7% vs 74.5%) and OM (73.7% vs 73.5%). However, calibration is lower for mENSAT than for AJCC. In consequence, no obvious benefit appears to be associated with the use of mENSAT relative to AJCC in US ACC patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: It is unknown whether 5-year overall survival (OS) differs and to what extent between the American Joint Committee on Cancer stage III non-seminoma testicular germ cell tumor (NS-TGCT) patients and simulated age-matched male population-based controls, according to race/ethnicity groups., Methods: We identified newly diagnosed (2004-2014) stage III NS-TGCT patients within the Surveillance Epidemiology and End Results database 2004-2019. For each case, we simulated an age-matched male control (Monte Carlo simulation), relying on Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS rates between stage III NS-TGCT patients and simulated age-matched male population-based controls, according to race/ethnicity groups (Caucasian, Hispanic, Asian/Pacific Islander and African American). Both, cancer-specific mortality (CSM) and other-cause mortality (OCM) were computed., Results: Of 2054 stage III NS-TGCT patients, 60% were Caucasians versus 33% Hispanics versus 4% Asians/Pacific Islanders versus 3% African Americans. The 5-year OS difference between stage III NS-TGCT patients versus simulated age-matched male population-based controls was highest in Asians/Pacific Islanders (64 vs. 99%, Δ = 35%), followed by African Americans (66 vs. 97%, Δ = 31%), Hispanics (72 vs. 99%, Δ = 27%), and Caucasians (76 vs. 98%, Δ = 22%). The 5-year CSM rate was highest in Asians/Pacific Islanders (32%), followed by African Americans (26%), Hispanics (25%), and Caucasians (20%). The 5-year OCM rate was highest in African Americans (8%), followed by Caucasians (4%), Asians/Pacific Islanders (4%), and Hispanics (2%)., Conclusion: Relative to SSA Life Tables, the highest 5-year OS disadvantage applied to stage III NS-TGCT Asian/Pacific Islander race/ethnicity group, followed by African American, Hispanic and Caucasian, in that order., (© 2024 The Japanese Urological Association.)

Purpose: We investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States., Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group [IGCCCG] prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection [RPLND] status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used., Results: In 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004)., Conclusion: We identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management., Competing Interests: Disclosures The authors declare that they have no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background/objectives: Solitary fibrous tumors (SFTs) represent a rare mesenchymal malignancy that can occur anywhere in the body. Due to the low prevalence of the disease, there is a lack of contemporary data regarding patient demographics and cancer-control outcomes., Methods: Within the SEER database (2000-2019), we identified 1134 patients diagnosed with malignant SFTs. The distributions of patient demographics and tumor characteristics were tabulated. Cumulative incidence plots and competing risks analyses were used to estimate cancer-specific mortality (CSM) after adjustment for other-cause mortality., Results: Of 1134 SFT patients, 87% underwent surgical resection. Most of the tumors were in the chest (28%), central nervous system (22%), head and neck (11%), pelvis (11%), extremities (10%), abdomen (10%) and retroperitoneum (6%), in that order. Stage was distributed as follows: localized (42%) vs. locally advanced (35%) vs. metastatic (13%). In multivariable competing risks models, independent predictors of higher CSM were stage (locally advanced HR: 1.6; metastatic HR: 2.9), non-surgical management (HR: 3.6) and tumor size (9-15.9 cm HR: 1.6; ≥16 cm HR: 1.9)., Conclusions: We validated the importance of stage and surgical resection as independent predictors of CSM in malignant SFTs. Moreover, we provide novel observations regarding the independent importance of tumor size, regardless of the site of origin, stage and/or surgical resection status.

Background/Objectives : The impact of surgical resection versus non-resection on cancer-specific mortality (CSM) in soft tissue pelvic sarcoma remains largely unclear, particularly when considering histologic subtypes such as liposarcoma, leiomyosarcoma, and sarcoma NOS. The objective of the present study was to first report data regarding the association between surgical resection status and CSM in soft tissue pelvic sarcoma. Methods : Using data from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019, we identified 2491 patients diagnosed with pelvic soft tissue sarcoma. Cumulative incidence plots were used to illustrate CSM and other-cause mortality rates based on the histologic subtype and surgical resection status. Competing risk regression models were employed to assess whether surgical resection was an independent predictor of CSM in both non-metastatic and metastatic patients. Results : Among the 2491 patients with soft tissue pelvic sarcoma, liposarcoma was the most common subtype (41%), followed by leiomyosarcoma (39%) and sarcoma NOS (20%). Surgical resection rates were 92% for liposarcoma, 91% for leiomyosarcoma, and 58% for sarcoma NOS in non-metastatic patients, while for metastatic patients, the rates were 55%, 49%, and 23%, respectively. In non-metastatic patients who underwent surgical resection, five-year CSM rates by histologic subtype were 10% for liposarcoma, 32% for leiomyosarcoma, and 27% for sarcoma NOS. The multivariable competing risk regression analysis showed that surgical resection provided a protective effect across all histologic subtypes in non-metastatic patients (liposarcoma HR: 0.2, leiomyosarcoma HR: 0.5, sarcoma NOS HR: 0.4). In metastatic patients, surgical resection had a protective effect for those with leiomyosarcoma (HR: 0.6) but not for those with sarcoma NOS. An analysis for metastatic liposarcoma was not possible due to insufficient data. Conclusions: In non-metastatic soft tissue pelvic sarcoma, surgical resection may be linked to a reduction in CSM. However, in metastatic patients, this protective effect appears to be limited primarily to those with leiomyosarcoma.

Purpose: It is unknown to what extent 10-year overall survival of radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients differs from age- and sex-matched population-based controls, especially when race/ethnicity is considered (Caucasian vs. African American vs. Hispanic vs. Asian/Pacific Islander)., Methods: We relied on the SEER database (2004-2018) to identify newly diagnosed radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients. For each case, we simulated an age- and sex-matched control relying on Social Security Administration Life Tables with 10 years of follow-up. We compared overall survival between renal carcinoma cases and population-based controls. Multivariable competing risks regression models tested for predictors of cancer-specific mortality versus other-cause mortality., Results: Of 6877 radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients, 5050 (73%) were Caucasian versus 433 (6%) African American versus 1002 (15%) Hispanic versus 392 (6%) Asian/Pacific Islanders. At 10 years, overall survival difference between radical nephrectomy treated intermediate/high risk non-metastatic clear cell renal carcinoma patients versus population-based controls was greatest in African Americans (51% vs. 81%, Δ = 30%), followed by Hispanics (54% vs. 80%, Δ = 26%), Asian/Pacific Islanders (56% vs. 80%, Δ = 24%) and Caucasians (52% vs. 74%, Δ = 22%). In competing risks regression, only African Americans exhibited significantly higher other cause mortality (hazard ratio = 1.3; 95% confidence interval = 1.1 - 1.6; p = 0.01) than others., Conclusion: Relative to Life Tables' derived sex- and age-matched controls, radical nephrectomy treated intermediate/high-risk non-metastatic clear cell renal carcinoma patients exhibit worse overall survival, with worst overall survival recorded in African Americans of all race/ethnicity groups., (© 2024 Wiley Periodicals LLC.)

Context: Although complete surgical resection provides the only means of cure in adrenocortical carcinoma (ACC), the magnitude of the survival benefit of adrenalectomy in metastatic ACC (mACC) is unknown., Objective: To assess the effect of adrenalectomy on survival outcomes in patients with mACC in a real-world setting., Design and Setting: Patients with mACC were identified within the Surveillance, Epidemiology, and End Results database (SEER 2004-2020) and we tested for differences according to adrenalectomy status., Patients: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between 2004-2020., Intervention: Primary tumor resection status (Adrenalectomy vs no-adrenalectomy)., Main Outcome and Measures: Kaplan-Meier plots, multivariable Cox regression models and landmark analyses were used. Sensitivity analyses focused on use of systemic therapy, contemporary (2012-2020) vs. historical (2004-2011), single vs. multiple metastatic sites and assessable specific solitary metastatic sites (lung only and liver only)., Results: Of 543 patients with mACC, 194 (36%) underwent adrenalectomy. In multivariable analyses, adrenalectomy was associated with lower overall mortality without (hazard ratio [HR]: 0.39; p<0.001), as well as with three months' landmark analyses (HR: 0.57, p=0.002). The same association effect with three months' landmark analyses was recorded in patients exposed to systemic therapy (HR: 0.49, p<0.001), contemporary patients (HR: 0.57, p=0.004), historical patients (HR: 0.42 , p<0.001), and in those with lung only solitary metastasis (HR: 0.50, p=0.02). In contrast, no significant association was recorded in patients naïve to systemic therapy (HR: 0.68, p=0.3), those with multiple metastatic sites (HR: 0.55, p=0.07) and those with liver only solitary metastasis (HR: 0.98, p=0.9)., Conclusions: The current results indicate a potential protective effect of adrenalectomy in mACC, particularly in patients exposed to systemic therapy and those with lung-only metastases., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

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 T 2-4 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

Background: We hypothesized that the evolving treatment paradigms recommended based on phase III trials may have translated into improved overall survival (OS) in contemporary community-based patients with clear-cell metastatic renal cell carcinoma (ccmRCC) undergoing active treatment., Patients and Methods: Within the SEER database, contemporary (2017-2020) and historical (2010-2016) patients with ccmRCC treated with either systemic therapy (ST), cytoreductive nephrectomy (CN), or both (ST+CN) were identified. Univariable and multivariable Cox-regression models were used., Results: Overall, 993 (32%) contemporary versus 2,106 (68%) historical patients with ccmRCC were identified. Median OS was 41 months in contemporary versus 25 months in historical patients (Δ=16 months; P<.001). In multivariable Cox-regression analyses, contemporary membership was independently associated with lower overall mortality (hazard ratio [HR], 0.7; 95% CI, 0.6-0.8; P<.001). In patients treated with ST alone, median OS was 17 months in contemporary versus 10 months in historical patients (Δ=7 months; P<.001; multivariable HR, 0.7; P=.005). In patients treated with CN alone, median OS was not reached in contemporary versus 33 months in historical patients (Δ=not available; P<.001; multivariable HR, 0.7; P<.001). In patients treated with ST+CN, median OS was 38 months in contemporary versus 26 months in historical patients (Δ=12 months; P<.001; multivariable HR, 0.7; P=.003)., Conclusions: Contemporary community-based patients with ccmRCC receiving active treatment clearly exhibited better survival than their historical counterparts, when examined as one group, as well as when examined as separate subgroups according to treatment type. Treatment advancements of phase III trials seem to be applied appropriately outside of centers of excellence.

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., (© 2024 Wiley Periodicals LLC.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors of this paper have read and approved the final version submitted., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Disclosure None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: We tested the association between other-cause mortality and partial vs. radical nephrectomy in patients with T1a, T1b, and T2 renal cell carcinoma, across all patient ages., Material and Methods: Within the Surveillance, Epidemiology, and End Results database (2010-2020), patients with localized renal cell carcinoma stages (T1a-T1b-T2, N0, M0), who underwent partial or radical nephrectomy were identified. Only patients with tumor size 2 to 10 cm were included. Cumulative incidence plots and multivariable competing risks regression models were used., Results: Of 68,195 patients, 28,845 (42%) underwent partial nephrectomy vs. 39,350 (58%) radical nephrectomy. In T1a patients, 5-year other-cause mortality rates were 6% for partial nephrectomy vs. 11% for radical nephrectomy (Δ=5%). In T1a patients, partial nephrectomy independently predicted lower other-cause mortality, across all ages (HR: 0.73, P < .001). In age category subgroup analyses addressing T1a patients, in all age categories, partial nephrectomy invariably predicted lower other-cause mortality than radical nephrectomy: ≤59 years (HR: 0.67, P < .001); 60 to 69 years (HR: 0.70, P < .001); and ≥70 years (HR: 0.79, P < .001). Finally, in T1b patients, as well as in T2 patients, no other-cause mortality advantage was recorded for partial vs. radical nephrectomy: T1b (8 vs. 10%, Δ=2%); T2 (8 vs. 9%, Δ=1%)., Conclusions: Relative to radical nephrectomy, partial nephrectomy is associated with lower other-cause mortality in stage T1a renal cell carcinoma patients across all age categories, including the oldest patients. Conversely, no clinically meaningful other-cause mortality benefit was associated with partial nephrectomy in stages T1b or T2, regardless of age, including youngest patients., Competing Interests: Disclosure The authors declare that there are no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: It is unknown whether specific locations of visceral metastatic sites affect overall survival (OS) of metastatic prostate cancer (mPCa) patients. We tested the association between specific locations of visceral metastatic sites and OS in mPCa patients., Materials and Methods: Within Surveillance, Epidemiology and End Results database (2010-2016), survival analyses relied on specific locations of visceral metastases: lung only vs. liver only vs. brain only vs. ≥2 visceral sites. Kaplan-Meier plots and Cox regression models were fitted., Results: Of 1827 patients, 1044 (57%) harbored lung only visceral metastases vs. 457 (25%) liver only vs. 131 (7%) brain only vs. 195 (11%) ≥2 visceral sites. Median OS was 22 months in all patients vs. 33 months in lung only vs. 15 months in liver only vs. 16 months in brain only vs. 15 months in patients with ≥2 visceral sites. Highest OS was recorded in lung only visceral metastases patients, especially when concomitant nonvisceral metastases were located in lymph nodes only (median OS 57 months) vs. bone only (26 months) vs. lymph nodes and bone (28 months). Liver only, brain only or ≥2 visceral sites exhibited poor OS, regardless of concomitant nonvisceral metastases type (median OS from 13 to 19 months)., Conclusion: In mPCa patients, lung only visceral metastases, especially when associated with lymph node only nonvisceral metastases, portend the best prognosis. Conversely, visceral metastatic sites other than lung portend poor prognosis, regardless of concomitant nonvisceral metastases type., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To test the prognostic significance of radiographic cN-stage in metastatic renal cell carcinoma (mRCC) patients with low metastatic burden (1 site of metastasis), relying on the Surveillance, Epidemiology, and End Results database (SEER 2010-2020)., Methods: Included were mRCC patients with 1 site of metastasis, treated with systemic therapy without cytoreductive nephrectomy (CN). Kaplan-Meier plots and multivariable Cox-regression models addressed cancer-specific mortality (CSM) according to radiographic cN-stage (ccN1 vs. ccN0). Separate subgroup analyses were performed, addressing radiographic N-stage in patients with distinct histology (clear-cell vs. RCC not otherwise specified [RCC NOS])., Results: Of 1756 mRCC patients, 545 (31%) were radiographic cN1. Overall, the median CSM-free survival of the cohort was 11 months. Median CSM-free survival was 8 vs. 14 months in radiographic cN1 vs. cN0 mRCC patients (HR 1.49, P < .0001). In multivariable Cox regression analyses, radiographic cN1 status was an independent predictor of higher CSM (HR 1.39; P = .01). In subgroup analyses, addressing patients with clear-cell histology and patients with RCC NOS separately, radiographic cN1 status remained independently associated with a higher CSM in both groups (clear-cell: HR 1.36; P = .03; RCC NOS: HR 2.06; P = .009)., Conclusion: In mRCC patients with low metastatic burden, presence or absence of radiographic lymph node invasion results in a clinically meaningful discrimination between those with poor prognosis and others. In consequence, consideration of radiographic lymph node invasion might be of great value in this specific population of mRCC patients., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To assess whether 5-year overall survival (OS) of squamous cell carcinoma of the penis (SCCP) patients differs from age-matched male population-based controls., Methods: We relied on the Surveillance Epidemiology and End Results database (2004-2018) to identify newly diagnosed (2004-2013) SCCP patients. For each case, we simulated an age-matched control (Monte Carlo simulation), relying on the Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS between SCCP patients and population-based controls in a stage-specific fashion. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) versus other-cause mortality (OCM)., Results: Of 2282 SCCP patients, the stage distribution was as follows: stage I 976 (43%) versus stage II 826 (36%) versus stage III 302 (13%) versus stage IV 178 (8%). At 5 years, OS of SCCP patients versus age-matched population-based controls was as follows: stage I 63% versus 80% (Δ = 17%), stage II 50% versus 80% (Δ = 30%), stage III 39% versus 84% (Δ = 45%), stage IV 26% versus 87% (Δ = 61%). At 5 years, CSM versus OCM in SCCP patients according to stage was as follows: stage I 12% versus 24%, stage II 22% versus 28%, stage III 47% versus 14%, and stage IV 60% versus 14%., Conclusion: SCCP patients exhibit worse OS across all stages. The difference in OS at 5 years between SCCP and age-matched male population-based controls ranged from 17% to 61%. At 5 years, CSM accounted for 12% to 60% of all deaths, across all stages., (© 2023 The Japanese Urological Association.)

Background: It is unknown whether previously reported other-cause mortality (OCM) advantage of partial cytoreductive nephrectomy (PCN) vs. radical cytoreductive nephrectomy (RCN) still applies to contemporary clear cell metastatic renal cell carcinoma (ccmRCC) patients., Materials and Methods: We relied on the Surveillance, Epidemiology and End Results (SEER) database (2004-2019) to identify ccmRCC patients treated with PCN and RCN. Temporal trends of PCN rates within the SEER database were tabulated. After propensity score matching (PSM), cumulative incidence plots depicted 5-year OCM and cancer-specific mortality (CSM) of PCN and RCN patients. Multivariable Cox regression models tested for differences between PCN vs. RCN., Results: Of 5149 study patients, 237 (5%) underwent PCN vs. 4912 (95%) RCN. In the SEER database 2004 to 2019, rates of PCN in ccmRCC patients increased from 3.0% to 8.0% (estimated annual percent change [EAPC]: 3.0%; P = .04). After PSM, 5-year OCM rates were 2.4 vs. 7.5% for respectively PCN vs. RCN patients (P = .036). 5-year CSM rates were 50.8 vs. 53.6% for respectively PCN and RCN patients (P = .57). In multivariable Cox regression models, PCN was associated with lower OCM (Hazard Ratio (HR): 0.39; 95% confidence interval (CI): 0.18-0.84; P = .02) but did not affect CSM rates (HR: 0.99; 95% CI: 0.76-1.29; P = .96)., Conclusions: We confirm the existence of OCM advantage after PCN vs. RCN in contemporary ccmRCC patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The prognostic significance of number and location of organ-specific metastatic sites in treated metastatic clear cell renal carcinoma (ccmRCC) patients is object of debate. The current study aimed to test the association between number and location of organ-specific metastatic sites and overall survival (OS) in ccmRCC., Materials and Methods: Within Surveillance, Epidemiology and End Results database (2010-2018), all ccmRCC patients treated with cytoreductive nephrectomy and/or systemic therapy were identified. Kaplan-Meier plots and Cox regression models focused on: A). number of organ-specific metastatic sites: solitary vs. 2 vs. 3 or more; B). solitary organ-specific metastatic sites (lung vs. bone vs. liver vs. brain); C). combinations of 2 and 3 or more different organ-specific metastatic sites., Results: Of 4,527 patients (median OS: 19 months), 3,054 (67%) harbored solitary organ-specific metastatic sites (27 months) vs. 1,153 (25%) combinations of 2 different organ-specific metastatic sites (12 months) vs. 320 (8%) combinations of 3 or more different organ-specific metastatic sites (7 months). In patients with solitary organ-specific metastatic sites, bone metastases portended the longest median OS (median OS: 31 months) vs. liver metastases portended the shortest median OS (16 months). Both were independent predictors of OS (multivariable hazard ratio, bone: 0.87; liver: 1.21). Median OS was similarly poor in patients with combinations of 2 different organ-specific metastatic sites (9-13 months), regardless of their location. The same pattern applied to patients with combinations of 3 or more different organ-specific metastatic sites (6-7 months)., Conclusions: Solitary organ-specific metastatic sites portend the most favorable OS (16-31 months). Solitary bone metastases yield the longest vs. liver metastases the shortest OS. Invariably poor OS applies to combinations of 2 (9-13 months), as well as 3 or more different organ-specific metastatic sites (6-7 months), regardless of their location., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study aimed to test the prognostic significance of pathologically confirmed lymph node invasion in metastatic renal cell carcinoma (mRCC) patients in this immunotherapy era., Methods: Surgically treated mRCC patients were identified in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2018. Kaplan-Meier plots and multivariable Cox-regression models were fitted to test for differences in cancer-specific mortality (CSM) and overall mortality (OM) according to N stage (pN0 vs pN1 vs. pNx). Subgroup analyses addressing pN1 patients tested for CSM and OM differences according to postoperative systemic therapy status., Results: Overall, 3149 surgically treated mRCC patients were identified. Of these patients, 443 (14%) were labeled as pN1, 812 (26%) as pN0, and 1894 (60%) as pNx. In Kaplan-Meier analyses, the median CSM-free survival was 15 months for pN1 versus 40 months for pN0 versus 35 months for pNx (P < 0.001). In multivariable Cox regression analyses, pN1 independently predicted higher CSM (hazard ratio [HR], 1.88; P < 0.01) and OM (HR, 1.95; P < 0.01) relative to pN0. In sensitivity analyses addressing pN1 patients, postoperative systemic therapy use independently predicted lower CSM (HR, 0.73; P < 0.01) and OM (HR, 0.71; P < 0.01)., Conclusion: Pathologically confirmed lymph node invasion independently predicted higher CSM and OM for surgically treated mRCC patients. For pN1 mRCC patients, use of postoperative systemic therapy was associated with lower CSM and OM. Consequently, N stage should be considered for individual patient counseling and clinical decision-making. Consort diagram of the study population., (© 2023. The Author(s).)

Background: It is unknown whether five-year overall survival (OS) differs and to what extent between testicular germ-cell tumor (TGCT) patients and age-matched male population-based controls., Materials: We identified newly diagnosed (2004-2014) TGCT patients within Surveillance Epidemiology and End Results database 2004-2019. We compared OS between non-seminoma (NS-TGCT) and seminoma (S-TGCT) patients relative to age-matched male population-based controls based on Social Security Administration Life-Tables. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) vs. other-cause mortality (OCM)., Results: Of all 20,935 TGCT patients, 43% had NS-TGCT and 57% had S-TGCT. Of NS-TGCT patients, 63% were stage I vs. 16% stage II vs. 21% stage III. Of S-TGCT patients, 86% were stage I vs. 8% were stage II vs. 6% stage III. Five-year OS differences between NS-TGCT patients vs age-matched male population-based controls were 97 vs. 99% (Δ = 2%) for stage I, 96 vs. 99% (Δ = 3%) for stage II, 76 vs 98% (Δ = 22%) for stage III. Five-year OS differences between S-TGCT patients vs age-matched male population-based controls were 97 vs. 98% (Δ = 1%) for stage I, 95 vs. 97% (Δ = 2%) for stage II, 87 vs. 98% (Δ = 11%) for stage III. OCM rates ranged from 1 to 3% in NS-TGCT patients and from 2 to 4% in S-TGCT patients., Conclusion: The OS difference between NS-TGCT patients vs. age-matched male population-based controls was invariably higher across all stages (2-22%) than for S-TGCT patients (1-11%). Reassuringly, OCM rates were marginal in stage I and stage II patients. Conversely, higher OCM rates were recorded in stage III patients., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: To test cancer-specific mortality (CSM) differences in specimen-confined (pT2) prostate cancer (PCa) at radical prostatectomy (RP) with lymph node dissection (LND) according to lymph node invasion (LNI)., Methods: RP + LND pT2 PCa patients were identified (surveillance, epidemiology, and end results 2010-2015). CSM-FS rates were tested in Kaplan-Meier plots and multivariable Cox-regression (MCR) models. Sensitivity analyses respectively addressing patients with 6 or more lymph nodes analyzed and pT2 pN1 patients were performed., Results: Overall, 32,258 patients with pT2 PCa at RP + LND were identified. Of these, 448 (1.4%) patients harbored LNI. Five-year CSM-free estimates were 99.6% for pN0 vs. 96.4% for pN1 (P < .001). In MCR models, pN1 (HR: 3.4, P < .001) independently predicted higher CSM. In sensitivity analyses addressing patients with 6 or more lymph nodes analyzed (n = 15,437), 328 (2.1%) pN1 patients were identified. In this subgroup, 5-year CSM-free estimates were 99.6% for pN0 vs. 96.3% for pN1 (P < .001) and, in MCR models, pN1 independently predicted higher CSM (HR: 4.4, P < .001). In sensitivity analyses addressing pT2 pN1 patients, 5-year CSM-free estimates were 99.3, 100 and 84.8% for ISUP GG 1-3 vs. 4 vs. 5, respectively (P < .001)., Conclusions: In patients with pT2 PCa a small proportion harbor LNI (1.4%-2.1%). In such patients, CSM rate is higher (HR 3.4-4.4, P < .001). This higher CSM risk seems to virtually exclusively apply to ISUP GG5 patients (84.8% 5-year CSM-free rate)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study aimed to test for temporal trends of in-hospital venous thromboembolism (VTE) and pulmonary embolism (PE) after major urologic cancer surgery (MUCS)., Methods: In the Nationwide Inpatient Sample (NIS) database (2010-2019), this study identified non-metastatic radical cystectomy (RC), radical prostatectomy (RP), radical nephrectomy (RN), and partial nephrectomy (PN) patients. Temporal trends of VTE and PE and multivariable logistic regression analyses (MLR) addressing VTE or PE, and mortality with VTE or PE were performed., Results: Of 196,915 patients, 1180 (1.0%) exhibited VTE and 583 (0.3%) exhibited PE. The VTE rates increased from 0.6 to 0.7% (estimated annual percentage change [EAPC] + 4.0%; p = 0.01). Conversely, the PE rates decreased from 0.4 to 0.2% (EAPC - 4.5%; p = 0.01). No difference was observed in mortality with VTE (EAPC - 2.1%; p = 0.7) or with PE (EAPC - 1.2%; p = 0.8). In MLR relative to RP, RC (odds ratio [OR] 5.1), RN (OR 4.5), and PN (OR 3.6) were associated with higher VTE risk (all p < 0.001). Similarly in MLR relative to RP, RC (OR 4.6), RN (OR 3.3), and PN (OR 3.9) were associated with higher PE risk (all p < 0.001). In MLR, the risk of mortality was higher when VTE or PE was present in RC (VTE: OR 3.7, PE: OR  4.8; both p < 0.001) and RN (VTE: OR 5.2, PE: OR  8.3; both p < 0.001)., Conclusions: RC, RN, and PN predisposes to a higher VTE and PE rates than RP. Moreover, among RC and RN patients with either VTE or PE, mortality is substantially higher than among their VTE or PE-free counterparts., (© 2023. The Author(s).)

Purpose: To test for regional differences in clear cell metastatic renal cell carcinoma (ccmRCC) patients across the USA., Methods: The Surveillance, Epidemiology, and End Results (SEER) database (2000-2018) was used to tabulate patient (age at diagnosis, sex, race/ethnicity), tumor (N stage, sites of metastasis) and treatment characteristics (proportions of nephrectomy and systemic therapy), according to 12 SEER registries. Multinomial regression models, as well as multivariable Cox regression models, tested the overall mortality (OM) adjusting for those patient, tumor and treatment characteristics., Results: In 9882 ccmRCC patients, registry-specific patient counts ranged from 4025 (41%) to 189 (2%). Differences across registries existed for sex (24-36% female), race/ethnicity (1-75% non-Caucasian), N stage (N1 25-35%, NX 3-13%), proportions of nephrectomy (44-63%) and systemic therapy (41-56%). Significant inter-registry differences remained after adjustment for proportions of nephrectomy (46-63%) and systemic therapy (35-56%). Unadjusted 5-year OM ranged from 73 to 85%. In multivariable analyses, three registries exhibited significantly higher OM (SEER registry 5: hazard ratio (HR) 1.20, p = 0.0001; SEER registry 7:HR 1.15, p = 0.008M SEER registry 10: HR 1.15, p = 0.04), relative to the largest reference registry (n = 4025)., Conclusion: Important regional differences including patient, tumor and treatment characteristics exist, when ccmRCC patients included in the SEER database are studied. Even after adjustment for these characteristics, important OM differences persisted, which may require more detailed analyses to further investigate these unexpected differences., (© 2023. The Author(s).)

Introduction: We tested for regional-specific differences in patient, tumor and treatment characteristics as well as cancer-specific mortality (CSM) of squamous cell carcinoma of the penis (SCCP) patients, across the Surveillance, Epidemiology, and End Results (SEER) registries., Methods: The SEER database (2000-2018) was used to tabulate patient (age at diagnosis, race/ethnicity), tumor (stage, grade, N-stage) and treatment characteristics (proportions of primary tumor surgery, local lymph node surgery, systemic therapy), according to 12 SEER registries. Multinomial regression models, as well as multivariable Cox regression models tested for CSM differences, adjusting for patient, tumor and treatment characteristics., Results: In 5395 SCCP patients, registry-specific patient counts ranged from 2060 (38 %) to 64 (1 %). Differences across registries existed for race/ethnicity, stage, grade and N-stage. Additionally, in stage I-II SCCP patients, proportions of local tumor destruction (LTD) ranged from 19 % to 39 % and from 33 % to 61 % for partial penectomy. In stage III-IV SCCP patients, proportions of partial penectomy ranged from 40 % to 59 % and from 17 % to 50 % for radical penectomy. Local lymph node surgery ranged from 8 % to 24 % and proportions of systemic therapy ranged from 3 % to 14 %. Significant inter-registry differences remained, after adjustment for treatment proportions. Unadjusted five-year CSM ranged from 19 % to 32 %. In multivariable analyses, one registry exhibited significantly higher CSM (SEER registry 10, Hazard Ratio [HR] 1.48), relative to the largest reference registry (SEER registry 1, n = 2060)., Conclusion: Important regional differences including patient, tumor and treatment characteristics exist for SCCP patients across SEER registries. After multivariable adjustment, no differences in CSM were recorded, with the exception of one registry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: In many primaries other than non-seminoma testis cancer, the risk of death due to cancer decreases with increasing disease-free interval duration after initial diagnosis and treatment. This effect is known as conditional survival and is relatively unexplored in stage III non-seminoma patients, where it may matter most in clinical decision-making. We examined the effect of disease-free interval duration on overall survival in stage III non-seminoma patients., Materials and Methods: Within the Surveillance, Epidemiology, and End Results Database (2004-2018), stage III non-seminoma patients were identified. Multivariable Cox regression analyses and conditional survival models were applied., Results: Of 2,092 surgically treated stage III non-seminoma patients, 385 (18%) exhibited good vs. 558 (27%) intermediate vs. 1,149 (55%) poor prognosis. In multivariable Cox regression models, poor prognosis group independently predicted overall mortality (HR 3.3, P < 0.001). In conditional survival analyses based on 36 months' disease-free interval duration, 5-year overall survival estimates were as follows: good prognosis patients 96 vs. 89% at initial diagnosis without accounting for disease-free interval duration (Δ=+7); intermediate prognosis patients 94 vs. 85% at initial diagnosis without accounting for disease-free interval duration (Δ=+9); poor prognosis patients 94 vs. 65% at initial diagnosis without accounting for disease-free interval duration (Δ=+29)., Conclusions: Conditional survival estimates based on 36 months' disease-free interval duration provide a more accurate and more optimistic outlook for stage III non-seminoma patients than predictions defined at initial diagnosis, without accounting for disease-free interval duration., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

All primary urinary tract malignant melanoma (ureter vs. bladder vs. urethra) patients were identified from within the Surveillance, Epidemiology, and End Results (SEER) database 2000-2020. Kaplan-Maier plots depicted the overall survival (OS) rates. Univariable and multivariable Cox regression (MCR) models were fitted to test the differences in overall mortality (OM). In the overall cohort (n = 74), the median OS was 22 months. No statistically significant or clinically meaningful differences were recorded according to sex (female vs. male; p = 0.9) and treatment of the primary (endoscopic vs. surgical; p = 0.6). Conversely, clinically meaningful but not statistically significant ( p ≥ 0.05) differences were recorded according to the patient's age at diagnosis (≤80 vs. ≥80 years old; p = 0.2), marital status (married 26 vs. unmarried 16 months; p = 0.2), and SEER stage (localized 31 vs. regional 14 months; p = 0.4), and the type of systemic therapy (exposed 31 vs. not exposed 20 months; p = 0.06). Finally, in univariable and MCR analyses, after adjustment for the SEER stage and type of systemic therapy, tumor origin within the bladder was associated with a three-fold higher OM (Hazard ratio: 3.00; p = 0.004), compared to tumor origin within the urethra. In conclusion, primary urinary tract malignant melanoma patients have poor survival. Specifically, tumor origin within the bladder independently predicted a higher OM, even after adjustment for the SEER stage and systemic therapy status.

Background: Accurate prediction of cancer control outcomes in renal cell carcinoma (RCC) patients is important for counselling, follow-up planning, and selection of appropriate adjuvant trial designs., Objective: To develop and externally validate a novel contemporary population-based model for predicting cancer-specific mortality-free survival (CSM-FS) in surgically treated papillary RCC (papRCC) patients and to compare it with established risk categories (Leibovich 2018)., Design, Setting, and Participants: Within the Surveillance, Epidemiology, and End Results database (2004-2019), we identified surgically treated papRCC patients (n = 3978). The population was randomly divided into development (50%, n = 1989) and external validation (50%, n = 1989) cohorts. Of the external validation cohort, 97% (n = 1930) of patients were included in a head-to-head comparison of the Leibovich 2018 risk categories addressing nonmetastatic patients., Outcome Measurements and Statistical Analysis: Univariable Cox regression models tested the statistical significance in the prediction of CSM-FS. The most parsimonious model with the best validation metrics was selected as the multivariable nomogram. Accuracy, calibration, and decision curve analyses (DCAs) tested the Cox regression-based nomogram, as well as the Leibovich 2018 risk categories in the external validation cohort., Results and Limitations: Age at diagnosis, grade, T stage, N stage, and M stage qualified for inclusion in the novel nomogram. In external validation, the accuracy of the novel nomogram was 0.83 at 5 yr and 0.80 at 10 yr. In nonmetastatic patients, 5- and 10-yr accuracy of the novel nomogram was 0.77 and 0.76, respectively. Conversely, 5- and 10-yr accuracy of the Leibovich 2018 risk categories was 0.70 and 0.66, respectively. The novel nomogram exhibited smaller departures from ideal predictions in calibration plots and higher net benefit in DCAs, when it was compared with the Leibovich 2018 risk categories. Limitations include the retrospective nature of the study, absence of a central pathological review, and inclusion of only North American patients., Conclusions: The novel nomogram may represent a valuable clinical aid, when papRCC CSM-FS predictions are required., Patient Summary: We developed an accurate tool to predict death due to papillary kidney cancer in a North American population., (Copyright © 2023 European Association of Urology. All rights reserved.)

Background: It is unknown whether the survival benefit of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) applies to patients with primary tumor size ≤4 cm., Objective: To test the association between CN on overall survival (OS) of mRCC patients with primary tumor size ≤4 cm., Design, Setting, and Participants: Within the Surveillance, Epidemiology, and End Results (SEER) database (2006-2018), all mRCC patients with primary tumor size ≤4 cm were identified., Outcome Measurements and Statistical Analysis: Propensity score matching (PSM), Kaplan-Meier plots, multivariable Cox regression analyses, and 6-mo landmark analyses addressed OS according to CN status. Sensitivity analyses examined specific populations of special interest: systemic therapy exposed versus naïve, clear-cell (ccmRCC) versus non-clear-cell (non-ccmRCC) mRCC histology, historical (2006-2012) versus contemporary (2013-2018), and young (≤65 yr) versus old (>65 yr) patients., Results and Limitations: Of 814 patients, 387 (48%) underwent CN. After PSM, the median OS was 44 versus 7 mo (Δ = 37 mo; p < 0.001) in CN versus no-CN patients. CN was associated with higher OS in overall population (multivariable hazard ratio [HR]: 0.30; p < 0.001) as well as in landmark analyses (HR: 0.39; p < 0.001). In all sensitivity analyses, CN was independently associated with higher OS: systemic therapy exposed, HR: 0.38; systemic therapy naïve, HR: 0.31; ccmRCC, HR: 0.29; non-ccmRCC, HR: 0.37; historical, HR: 0.31; contemporary, HR: 0.30; young, HR: 0.23; and old, HR: 0.39 (all p < 0.001)., Conclusions: The current study validates the association between CN and higher OS in patients with primary tumor size ≤4 cm. This association is robust, controlled for immortal time bias, and valid across systemic treatment exposure, histologic subtypes, years of surgery, and patient age., Patient Summary: In the current study, we tested the association between cytoreductive nephrectomy (CN) and overall survival in patients with metastatic renal cell carcinoma and small primary tumor size. We found a strong association between CN and survival, which persists even after several significant variations in patient and tumor characteristics., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Despite advances in treatment, metastatic urothelial carcinoma of the urinary bladder (mUCUB) is associated with high mortality and treatment risk. We tested for regional differences in mUCUB within a large-scale, population-based database., Methods: Using the Surveillance, Epidemiology and End Results (SEER) database (2010-2018), patient (age, sex, race/ethnicity), tumor (T-stage, N-stage, number of metastatic sites), and treatment (systemic therapy, radical cystectomy) characteristics were tabulated for mUCUB patients according to 11 SEER registries. Multinomial regression models and multivariable Cox regression models tested overall mortality (OM), adjusting for patient, tumor and treatment characteristics., Results: In 4817 mUCUB patients, registry-specific patient counts ranged from 1855 (38.5%) to 105 (2.2%). Important inter-regional differences existed for race/ethnicity (3-36% for others than non-Hispanic Whites), N-stage (28-39% for N1-3, 44-58% in N0, 8-22% for unknown N-stage), systemic therapy (38-54%) and radical cystectomy (3-11%). In multivariable analyses adjusting for these patient, tumor, and treatment characteristics, one registry exhibited significantly lower OM (SEER registry 10: hazard ratio [HR] 0.83) and two other registries exhibited significantly higher OM (SEER registries 9: HR 1.13; SEER registry 8: HR 1.24) relative to the largest reference registry (n=1855)., Conclusions: We identified important regional differences that included patient, tumor, and treatment characteristics. Even after adjustment for these characteristics, important OM differences persisted, which may warrant more detailed investigation.

Background: We tested for regional differences across United States (US) in rates of adrenalectomy, systemic therapy, and adrenalectomy and systemic therapy combination for adrenocortical carcinoma (ACC) patients. We hypothesized that no differences exist, especially after accounting for baseline patient and tumor characteristics., Methods: Within Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), 1275 ACC patients were identified. Distribution of patient age, tumor size, ENSAT (European Network for the Study of Adrenal Tumors) stages, and treatments were tabulated and graphically displayed, according to nine geographical registries, corresponding to the population of specific states, cities or macro areas of the US on which the data are based on. Multinomial models predicted treatment probability for each patient according to registries., Results: Patients count according to registries ranged from 62 to 509. Differences across registries existed for age (range 54-59 years; P=0.4), tumor size (8.5-11.0 cm; P=0.2), ENSAT stage (1-11% vs. 17-35% vs. 18-32% vs. 24-44%, in respectively ENSAT stage I, II, III, and IV), and treatment distribution (35-53% vs. 5-21% vs. 23-42%, in respectively adrenalectomy, systemic therapy, and adrenalectomy and systemic therapy combination; P=0.039). After adjustment for age, stage and year of diagnosis, clinically meaningful residual differences across registries remained for adrenalectomy (33-54%), systemic therapy (4-19%), and adrenalectomy and systemic therapy combination (20-38%). However, most variability originated from registries with smallest sample sizes., Conclusions: We identified important variability in ACC treatment according to SEER geographical registries, even after considering baseline patient and tumor characteristics. These findings may be indicative of differences in quality of care or expertise in ACC management.

Purpose: To evaluate the association between radical cystectomy (RC) and cancer-specific mortality (CSM) in patients diagnosed with adenocarcinoma of the bladder (ACB). Moreover, to directly compare the survival advantage of RC between ACB vs. urothelial bladder cancer (UBC)., Materials and Methods: Non-metastatic muscle-invasive ACB and UBC patients were identified within Surveillance, Epidemiology, and End Results database (SEER 2000-2018). All analyses were stratified between RC vs. no-RC, in either organ-confined (OC: T 2 N 0 M 0 ) or non-organ-confined (NOC: T 3-4 N 0 M 0 or T any N 1-3 M 0 ) stages. Propensity score matching (PSM), cumulative incidence plots, competing risks regression (CRR) analyses, and 3 months' landmark analyses were performed., Results: Overall, 1,005 ACB and 47,741 UBC patients were identified, of whom 475 (47%) and 19,499 (41%) were treated with RC, respectively. After PSM, comparison between RC vs. no-RC applied to 127 vs. 127 OC-ACB, 7,611 vs. 7,611 OC-UBC, 143 vs. 143 NOC-ACB, and 4,664 vs. 4,664 NOC-UBC patients. 36-month CSM rates in RC vs. no-RC patients were 14 vs. 44% in OC-ACB, 18 vs. 39% in OC-UBC, 49 vs. 66% in NOC-ACB, and 44 vs. 56% in NOC-UBC patients. In CRR analyses, the effect of RC on CSM yielded a hazard ratio of 0.37 in OC-ACB, of 0.45 in OC-UBC, of 0.65 in NOC-ACB and of 0.68 in NOC-UBC patients (all P values<0.001). Landmark analyses virtually perfectly replicated the results., Conclusions: In ACB, regardless of stage, RC is associated with lower CSM. The magnitude of this survival advantage was greater in ACB than in UBC, even after control for immortal time bias., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim and Objectives : We aimed to test the impact of age on long-term urinary continence (≥12 months) in patients undergoing robotic-assisted radical prostatectomy. Methods and Materials : We relied on an institutional tertiary-care database to identify the patients who underwent robotic-assisted radical prostatectomy between January 2014 and January 2021. Patients were divided into three age groups: age group one (≤60 years), age group two (61-69 years) and age group three (≥70 years). Multivariable logistic regression models tested the differences between the age groups in the analyses addressing long-term urinary continence after robotic-assisted radical prostatectomy. Results : Of the 201 prostate cancer patients treated with robotic-assisted radical prostatectomy, 49 (24%) were assigned to age group one (≤60 years), 93 (46%) to age group two (61-69 years) and 59 (29%) to age group three (≥70 years). The three age groups differed according to long-term urinary continence: 90% vs. 84% vs. 69% for, respectively, age group one vs. two vs. three ( p = 0.018). In the multivariable logistic regression, age group one (Odds Ratio (OR) 4.73, 95% CI 1.44-18.65, p = 0.015) and 2 (OR 2.94; 95% CI 1.23-7.29; p = 0.017) were independent predictors for urinary continence, compared to age group three. Conclusion : Younger age, especially ≤60 years, was associated with better urinary continence after robotic-assisted radical prostatectomy. This observation is important at the point of patient education and should be discussed in informed consent.

Background: Guidelines recommend VENUSS and GRANT models for the prediction of cancer control outcomes after nephrectomy for nonmetastatic papillary renal cell carcinoma (pRCC)., Objective: To test the ability of VENUSS and GRANT models to predict 5-yr cancer-specific survival in a North American population., Design Setting and Participants: For this retrospective study, we identified 4184 patients with unilateral surgically treated nonmetastatic pRCC in the Surveillance, Epidemiology, and End Results database (2004-2019)., Outcome Measurements and Statistical Analysis: The original VENUSS and GRANT risk categories were applied to predict 5-yr cancer-specific survival. A cross-validation method was used to test the accuracy and calibration of the models and to conduct decision curve analyses for the study cohort., Results and Limitations: The VENUSS and GRANT categories represented independent predictors of cancer-specific mortality. On cross-validation, the accuracy of the VENUSS and GRANT risk categories was 0.73 and 0.65, respectively. Both models showed good calibration and performed better than random predictions in decision curve analysis. Limitations include the retrospective nature of the study and the absence of a central pathological review., Conclusion: VENUSS risk categories fulfilled prognostic model criteria for predicting cancer-specific survival 5 yr after surgery in North American patients with nonmetastatic pRCC as recommended by guidelines. Conversely, GRANT risk categories did not. Thus, VENUSS risk categories represent an important tool for counseling, follow-up planning, and patient selection for appropriate adjuvant trials in pRCC., Patient Summary: We tested the ability of two validated methods (VENUSS and GRANT) to predict death due to papillary kidney cancer in a North American population. The VENUSS risk categories showed good performance in predicting 5-year cancer-specific survival., (© 2023 The Authors.)

Background: Lymph node invasion (LNI) represents a poor prognostic factor after primary radical prostatectomy (RP) for prostate cancer (PCa). However, the impact of LNI on oncologic outcomes in salvage radical prostatectomy (SRP) patients is unknown., Objective: To investigate the impact of lymph node dissection (LND) and pathological lymph node status (pNX vs. pN0 vs. pN1) on long-term oncologic outcomes of SRP patients., Patients and Methods: Patients who underwent SRP for recurrent PCa between 2000 and 2021 were identified from 12 high-volume centers. Kaplan-Meier analyses and multivariable Cox regression models were used. Endpoints were biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS)., Results: Of 853 SRP patients, 87% ( n = 727) underwent LND, and 21% ( n = 151) harbored LNI. The median follow-up was 27 months. The mean number of removed lymph nodes was 13 in the LND cohort. At 72 months after SRP, BCR-free survival was 54% vs. 47% vs. 7.2% for patients with pNX vs. pN0 vs. pN1 ( p < 0.001), respectively. At 120 months after SRP, OS rates were 89% vs. 81% vs. 41% ( p < 0.001), and CSS rates were 94% vs. 96% vs. 82% ( p = 0.02) for patients with pNX vs. pN0 vs. pN1, respectively. In multivariable Cox regression analyses, pN1 status was independently associated with BCR (HR: 1.77, p < 0.001) and death (HR: 2.89, p < 0.001)., Conclusions: In SRP patients, LNI represents an independent poor prognostic factor. However, the oncologic benefit of LND in SRP remains debatable. These findings underline the need for a cautious LND indication in SRP patients as well as strict postoperative monitoring of SRP patients with LNI.

Background: To date, five trials testing the effect of adjuvant systemic therapy in surgically treated non-metastatic renal cell carcinoma included patients with non-clear cell histology. We tested the effect of papillary vs. chromophobe histological subtype, stage, and grade on 10-year cancer-specific survival, in patients eligible for ≥1 such trial., Methods: We identified patients meeting ASSURE, SORCE, EVEREST, PROSPER, or RAMPART trial inclusion criteria in the SEER (2000-2018) database. Kaplan-Meier analyses estimated 10-year survival rates and multivariable Cox regression models tested for the independent predictor status of histological subtype, stage, and grade., Results: We identified 5465 (68%) papillary and 2562 (32%) chromophobe renal cell carcinoma patients. Cancer-specific survival rates at 10 years were 77% in papillary vs. 90% in chromophobe. In multivariable Cox regression models applied to papillary patients, cancer-specific mortality independent predictor status was reached for T3G3-4 (HR 2.9), T4Gany (HR 3.4), TanyN1G1-2 (HR 3.1), and TanyN1G3-4 (HR 8.0, P<0.001), relative to T1/2Gany. In multivariable Cox regression models applied to chromophobe patients, mortality independent predictor status was reached for T3G3-4 (HR 3.6), T4Gany (HR 14.0), TanyN1G1-2 (HR 5.7), and TanyN1G3-4 (HR 15.0, P<0.001), relative to T1/2Gany., Conclusions: In surgically treated non-metastatic intermediate/high-risk renal cell carcinoma patients, papillary histologic subtype exhibited worse cancer-specific survival than chromophobe histologic subtype. Although stage and grade represented independent predictors in both histological subtype groups, the magnitude of their effect was invariably worse in chromophobe than in papillary patients. In consequence, papillary and chromophobe patients should be considered separate entities instead of being combined under the non-clear cell designation.

Purpose: To 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 Methods: Within 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, T 2 N 0 M 0 ) vs non-organ-confined stage (NOC, T 3-4 N 0 M 0 or T any N 1-3 M 0 ) 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., Results: Of 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%., Conclusions: Conditional 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., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We aimed to externally validate the SEER-based nomogram used to predict downgrading in biopsied high-risk prostate cancer patients treated with radical prostatectomy (RP) in a contemporary European tertiary-care-hospital cohort. We relied on an institutional tertiary-care database to identify biopsied high-risk prostate cancer patients in the National Comprehensive Cancer Network (NCCN) who underwent RP between January 2014 and December 2022. The model's downgrading performance was evaluated using accuracy and calibration. The net benefit of the nomogram was tested with decision-curve analyses. Overall, 241 biopsied high-risk prostate cancer patients were identified. In total, 51% were downgraded at RP. Moreover, of the 99 patients with a biopsy Gleason pattern of 5, 43% were significantly downgraded to RP Gleason pattern ≤ 4 + 4. The nomogram predicted the downgrading with 72% accuracy. A high level of agreement between the predicted and observed downgrading rates was observed. In the prediction of significant downgrading from a biopsy Gleason pattern of 5 to a RP Gleason pattern ≤ 4 + 4, the accuracy was 71%. Deviations from the ideal predictions were noted for predicted probabilities between 30% and 50%, where the nomogram overestimated the observed rate of significant downgrading. This external validation of the SEER-based nomogram confirmed its ability to predict the downgrading of biopsy high-risk prostate cancer patients and its accurate use for patient counseling in high-volume RP centers.

Purpose: It is unknown to what extent overall survival (OS) of organ-confined (T2N0M0) urothelial carcinoma of the urinary bladder (UCUB) patients differs from age- and sex-matched population-based controls, especially when treatment modalities such as radical cystectomy (RC), trimodal therapy (TMT), or radiotherapy (RT) are considered., Methods: Relying on the Surveillance Epidemiology and End Results database (2004-2018), we identified newly diagnosed (2004-2013) T2N0M0 UCUB patients treated with either RC, TMT or RT. For each case, we simulated an age- and sex-matched control (Monte Carlo simulation), relying on Social Security Administration Life Tables with 5 years of follow-up, and compared OS with that of RC-, TMT-, and RT-treated cases. Additionally, we relied on smoothed cumulative incidence plots to display cancer-specific mortality (CSM) and other-cause mortality (OCM) rates for each treatment modality., Results: Of 7153 T2N0M0 UCUB patients, 4336 (61%) underwent RC, 1810 (25%) TMT, and 1007 (14%) RT. At 5 years, OS rate in RC cases was 65% vs. 86% in population-based controls (Δ = 21%); in TMT cases, 32% vs. 74% in population-based controls (Δ = 42%); and in RT, 13% vs. 60% in population-based control (Δ = 47%). Five-year CSM rates were highest in RT (57%), followed by TMT (46%) and RC (24%). Five-year OCM rates were the highest in RT (30%), followed by TMT (22%) and RC (12%)., Conclusion: OS of T2N0M0 UCUB patients is substantially less than that of age- and sex-matched population-based controls. The biggest difference affects RT, followed by TMT. A modest difference was recorded in RC and population-based controls., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Within the Surveillance, Epidemiology, and End Results database (2000-2019), we identified 5522 unilateral surgically treated non-metastatic chromophobe kidney cancer (chRCC) patients. This population was randomly divided into development vs. external validation cohorts. In the development cohort, the original Leibovich 2018 and GRANT categories were applied to predict 5- and 10-year cancer-specific survival (CSS). Subsequently, a novel multivariable nomogram was developed. Accuracy, calibration and decision curve analyses (DCA) tested the Cox regression-based nomogram as well as the Leibovich 2018 and GRANT risk categories in the external validation cohort. The accuracy of the Leibovich 2018 and GRANT models was 0.65 and 0.64 at ten years, respectively. The novel prognostic nomogram had an accuracy of 0.78 at ten years. All models exhibited good calibration. In DCA, Leibovich 2018 outperformed the novel nomogram within selected ranges of threshold probabilities at ten years. Conversely, the novel nomogram outperformed Leibovich 2018 for other values of threshold probabilities. In summary, Leibovich 2018 and GRANT risk categories exhibited borderline low accuracy in predicting CSS in North American non-metastatic chRCC patients. Conversely, the novel nomogram exhibited higher accuracy. However, in DCA, all examined models exhibited limitations within specific threshold probability intervals. In consequence, all three examined models provide individual predictions that might be suboptimal and be affected by limitations determined by the natural history of chRCC, where few deaths occur within ten years from surgery. Further investigations regarding established and novel predictors of CSS and relying on large sample sizes with longer follow-up are needed to better stratify CSS in chRCC.

Background and Objectives: 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 surgically treated adrenocortical carcinoma (ACC) patients., Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2018), 867 ACC patients treated with adrenalectomy were identified. Conditional survival estimates at 5-years were assessed based on DFI duration and according to stage at presentation. Separate Cox regression models were fitted at baseline and according to DFI., Results: Overall, 406 (47%), 285 (33%), and 176 (20%) patients were stage I-II, III and IV, respectively. In conditional survival analysis, providing a DFI of 24 months, 5-year CSM-free survival at initial diagnosis increased from 66% to 80% in stage I-II, from 35% to 66% in stage III, and from 14% to 36% in stage IV. In multivariable Cox regression models, stage III (hazard ratio [HR]: 2.38; p < 0.001) and IV (HR: 4.67; p < 0.001) independently predicted higher CSM, relative to stage I-II. The magnitude of this effect decreased over time, providing increasing DFI duration., Conclusions: In surgically treated ACC, survival probabilities increase with longer DFI duration. This improvement is more pronounced in stage III, followed by stages IV and I-II patients, in that order. Survival estimates accounting for DFI may prove valuable in patients counseling., (© 2022 Wiley Periodicals LLC.)