Transition from Transrectal to Transperineal MRI-Fusion Prostate Biopsy Does Not Comprise Detection Rates of Clinically Significant Prostate Cancer at a Tertiary Care Center.

BACKGROUND: A remarkable paradigm shift has emerged regarding the preferred prostate biopsy approach, favoring the transperineal (TP) over the transrectal (TR) approach due to the reduced risk of severe urinary tract infections. However, its impact on the detection of clinically significant prostate cancer (csPCa) remains unclear. MATERIALS AND METHODS: We relied on a prospectively maintained tertiary care database to identify patients who underwent either TP or TR prostate biopsy between 01/2014 and 12/2023. Of those, only patients with suspicious magnetic resonance imaging (MRI) PIRADS lesions (Likert-scale: 3,4,5) received MRI-targeted and systematic biopsies. Detection rates of csPCa (International Society of Urological Pathology [ISUP] ≥ 2) were compared between biopsy approach (TP vs. TR) according to index lesion. Subsequently, uni- and multivariable logistic regression models were applied to investigate the predictive status of the biopsy approach within each subcohort. RESULTS: Of 2063 patients, 1118 (54%) underwent combined MRI-guided and systematic prostate biopsy and were included in the final cohort. Of those, 127 (11%) and 991 (89%) underwent TP vs. TR. CsPCa rates, regardless of differences in patients' demographics and distribution of index PIRDAS lesions, did not differ statistically significantly and were 51 vs. 52%, respectively (p = 0.8). CsPCa detection rates for PIRDAS-3, PIRADS-4 and PIRADS-5 did not differ and were 24 vs. 23%, 48 vs. 51% and 72 vs. 76% for PIRADS-3, PIRADS-4 and PIRADS-5 subgroups for TP vs. TR, respectively (all p ≥ 0.9) Conclusions: The current results support the available data indicating that TP biopsy approach is comparable to transrectal biopsy approach regarding csPCa detection rates.

First-Line Immune Combination Therapies for Nonclear Cell Versus Clear Cell Metastatic Renal Cell Carcinoma: Real-World Multicenter Data From Germany.

INTRODUCTION: The aim was to compare treatment outcomes of clear cell metastatic renal cell carcinoma (ccmRCC) versus non-ccmRCC (nccmRCC) patients who received first-line immune combination therapies. MATERIALS AND METHODS: Within our retrospective multi-institutional consecutive database of eight tertiary-care centers, we identified mRCC patients treated with first-line immune combination therapies between 11/2017 and 12/2022. Using log-rank analysis and multivariable Cox regression, we tested for differences in overall survival (OS) and progression-free survival (PFS) of nccmRCC versus ccmRCC patients. Covariables consisted of age at diagnosis, sex, International Metastatic Renal Cell Carcinoma Database Consortium risk groups, Eastern Cooperative Oncology Group status, and sarcomatoid feature. RESULTS: Of 289 study patients, 39 (13%) patients harbored nccmRCC. Median OS was 37 months versus not reached for ccmRCC versus nccmRCC patients (P = .6). Median PFS was 13 versus 15 months (P = .9). Multivariable Cox regression models did not identify nccmRCC as an independent predictor of higher overall mortality in mRCC patients (hazard ratio [HR]: 1.23; P = .6) or a higher progression rate (HR: 1.0; P = 1.0). CONCLUSION: In our real-world multi-institutional study, no differences in OS and PFS between ccmRCC and nccmRCC patients receiving first-line immune combination treatment were observed, even after adjustment for important patient and tumor characteristics. More prospective trials in nccmRCC patients are needed.

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.

Impact of PSA nadir, PSA response and time to PSA nadir on overall survival in real-world setting of metastatic hormone-sensitive prostate cancer patients.

BACKGROUND: To evaluate the impact of prostate-specific antigen (PSA) nadir, PSA response and time to PSA nadir (TTN) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies. METHODS: Different PSA nadir cut-offs (including ultra-low PSA) were tested for OS analyses. Additionally, PSA response ≥99% was evaluated, as well as TTN categorized as <3 versus 3-6 versus 6-12 versus >12 months. Multivariable Cox regression models predicted the value of PSA nadir cut-offs, PSA response and TTN on OS. Sensitivity analyses were performed in de novo and high volume mHSPC patients. RESULTS: Of 238 eligible patients, PSA cut-offs of <0.2 versus 0.2-4.0 versus >4.0 ng/mL differed significantly regarding median OS (96 vs. 56 vs. 44 months, p < 0.01), as well as in subgroup analyses of de novo mHSPC patients and multivariable Cox regression models. A more stringent PSA cut-off of <0.02 versus 0.02-0.2 versus >0.2 ng/mL also yielded significant median OS differences (not reached vs. 96 vs. 50 months, p < 0.01), even after additional multivariable adjustment. A PSA response ≥99% was also significantly associated with better OS than counterparty with <99% response, even after multivariable adjustment (both p < 0.02). When TTN groups were compared, patients with longer TTN harbored more extended OS than those with short TTN (<3 vs. 3-6 vs. 6-12 vs. >12 months: 34 vs. 50 vs. 67 vs. 96 months, p < 0.01). Virtually similar results were observed in sensitivity analyses for high volume mHSPC patients. CONCLUSIONS: In times of combination therapies for mHSPC, a PSA nadir of respectively, <0.2 and <0.02 ng/mL are associated with best OS rates. Moreover, a relative PSA response ≥99% and a longer TTN are clinical important proxies for favorable OS estimates.

Real-world evidence of tumor and patient characteristics and survival with avelumab maintenance after chemotherapy for advanced and metastatic urothelial carcinoma.

PURPOSE: Despite the prospective randomized controlled JAVELIN Bladder 100 trial, no real-world evidence exists regarding tumor characteristics, adverse events (AE) and survival of avelumab maintenance (AVM) treated patients with partial/complete response or stable disease after previous platinum-based chemotherapy for advanced/metastatic urothelial carcinoma (mUC). METHODS: We relied on our institutional database to identify mUC patients who received AVM between 01/2021-12/2023. The main outcomes consisted of overall (OS) and progression-free survival (PFS) and were computed by Kaplan-Meier estimates. Stratification was performed according to PD-L1 status. RESULTS: Overall, 24 AVM patients were identified at a median age of 71 (interquartile range [IQR]: 67-76) years of which 67% were males. Of these, 63%, 21% and 17% received AVM therapy for bladder cancer and upper tract urothelial carcinoma or both, respectively. PD-L1 status was positive in 45% of patients. During AVM treatment, AEs were observed in 33% of patients, however, were limited to ≤2 grade AEs. At a median follow-up of eight (IQR 4-20) months, 71% of patients had progressed under AVM with median PFS of 6.2 months (CI: 3.2-18.2). Median OS was 13.4 (CI: 6.9-not reached [NR]) months. One-year OS after AVM was 52%. In PD-L1 positive patients, median PFS and OS were 6.4 (CI: 2.7 - NR) months and 13.4 (CI: 7.7 months - NR), respectively. CONCLUSION: AVM is associated with moderate AE rates. Despite similarities in baseline characteristics compared to trial-selected JAVELIN Bladder 100 mUC patients, AVM resulted in longer/similar PFS but significantly shorter OS in in real-world setting.

Feasibility of Next-generation Sequencing of Liquid Biopsy (Circulating Tumor DNA) Samples and Tumor Tissue from Patients with Metastatic Prostate Cancer in a Real-world Clinical Setting in Germany.

BACKGROUND AND OBJECTIVE: With European Medicines Agency approval of PARP inhibitors in metastatic castration-resistant prostate cancer and ongoing trials in metastatic hormone-sensitive prostate cancer, detection of genetic alterations in BRCA1/2 and other homologous recombination repair genes has gained an important role. Our aim was to investigate the feasibility and comparability of comprehensive next-generation sequencing (NGS) of liquid biopsy (LB; circulating tumor DNA) and tumor tissue (TT) samples in a real-world clinical setting. METHODS: The study cohort consisted of 50 patients with metastatic prostate cancer (mPC) who had TT NGS performed for BRCA1/2 alterations and consent for additional LB NGS. The Oncomine Comprehensive Assay v3 (Thermo Fisher Scientific, Waltham, MA, USA) was used for TT NGS. The Guardant360 83-gene assay (Guardant Health, Palo Alto, CA, USA) was used for LB NGS, including all types of somatic alterations, microsatellite instability, and blood tumor mutational burden. We calculated BRCA1/2 alteration rates and the negative percentage agreement (NPA) and positive percentage agreement (PPA) between TT and LB results. KEY FINDINGS AND LIMITATIONS: TT NGS was successful in 44/50 patients (88%), with pathogenic BRCA1/2 alterations detected in four (9%). LB NGS was successful in all 50 patients (100%), with BRCA1/2 alterations detected in ten (20%). In a subgroup analysis for the 44 patients with successful TT NGS, NPA was 85% and PPA was 50%. The median time between TT sample collection and blood sampling for NGS was 132 wk (IQR 94-186). The limited sample size and differences in the time of NGS assessment are limitations. CONCLUSIONS AND CLINICAL IMPLICATIONS: LB NGS resulted in a higher detection rate for BRCA1/2 alterations in comparison to conventional TT NGS (20% vs 9%). Ideally, BRCA1/2 testing should be based on both approaches to identify all patients with mPC eligible for PARP inhibitor therapy. PATIENT SUMMARY: Our study shows that genetic tests for both tumor tissue and blood samples results in higher rates of detection of BRCA1/2 gene alterations in patients with metastatic prostate cancer.

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.

Differences in Survival of Clear Cell Metastatic Renal Cell Carcinoma According to Partial vs. Radical Cytoreductive Nephrectomy.

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.

Survival of patients with clear cell renal carcinoma according to number and location of organ-specific metastatic sites.

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.

Overall Survival of Metastatic Prostate Cancer Patients According to Location of Visceral Metastatic Sites.

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.

Metastatic Squamous Cell Carcinoma of the Urinary Bladder: Urgent Call for New Therapies.

BACKGROUND: Squamous cell carcinoma (SCC) of the urinary bladder is the most common non-urothelial variant histology. Currently, upfront radical cystectomy is the gold standard for non-metastatic SCC of the bladder. However, several studies have shown that SCC of the bladder is associated with higher aggressiveness and worse survival outcomes, such as progression-free and cancer-specific survival, relative to the urothelial histological subtype. Moreover, metastatic SCC seems to poorly respond to systemic treatments and/or radiotherapy. SUMMARY: This review summarizes the current knowledge and medical evidence regarding local and systematic treatment of mSCC of the bladder, including a case series of four initially locally advanced and later metastatic SCC patients of our tertiary care hospital. KEY MESSAGES: Despite being the second most common variant histology of bladder cancer, current therapies for SCC do not provide satisfactory therapeutic responses.

Impact of consensus molecular subtypes on survival with and without adjuvant chemotherapy in muscle-invasive urothelial bladder cancer.

AIMS: Adjuvant chemotherapy after radical cystectomy can reduce the risk of recurrence and death in advanced muscle-invasive urothelial bladder cancer (MIBC). Molecular subtypes have been shown to be associated with survival. However, their predictive value to guide treatment decisions is controversial and data to use subtypes as guidance for adjuvant chemotherapy is sparse. We aimed to assess survival rates based on MIBC consensus molecular subtypes with and without adjuvant chemotherapy. METHODS: Gene expression profiles of 143 patients with MIBC undergoing radical cystectomy were determined from formalin-fixed, paraffin-embedded specimen to assign consensus molecular subtypes. Expression of programmed cell death ligand-1 (PD-L1) and immune cell infiltration were determined using multiplex immunofluorescence. Matched-pair analysis was performed to evaluate the effect of adjuvant chemotherapy on overall survival (OS) for molecular subtypes applying Kaplan-Meier and Cox regression survival analyses. RESULTS: Samples were luminal papillary: 9.1% (n=13), luminal non-specified: 6.3% (n=9), luminal unstable: 4.9% (n=7), stroma-rich: 27.9% (n=40), basal/squamous (Ba/Sq): 48.9% (n=70) and neuroendocrine-like (NE-like): 2.8% (n=4). Ba/Sq tumours had the highest concentration of PD-L1+ tumour and immune cells. Patients with luminal subtypes had better OS than those with NE-like (HR 0.2, 95% CI 0.1 to 0.7, p<0.05) and Ba/Sq (HR 0.5, 95% CI 0.2 to 0.9, p<0.05). No survival benefit with adjuvant chemotherapy was observed for luminal tumours, whereas Ba/Sq had significantly improved survival rates with adjuvant chemotherapy. Retrospective design and sample size are the main limitations. CONCLUSION: Consensus molecular subtypes can be used to stratify patients with MIBC. Luminal tumours have the best prognosis and less benefit when receiving adjuvant chemotherapy compared with Ba/Sq tumours.

Differences in long-term continence rates between prostate cancer patients with extraprostatic vs. organ-confined disease undergoing robotic-assisted radical prostatectomy: An observational studys.

OBJECTIVES: Within the tertiary-case database, the authors tested for differences in long-term continence rates (≥ 12 months) between prostate cancer patients with extraprostatic vs. organ-confined disease who underwent Robotic-Assisted Radical Prostatectomy (RARP). METHOD: In the institutional tertiary-care database the authors identified prostate cancer patients who underwent RARP between 01/2014 and 01/2021. The cohort was divided into two groups based on tumor extension in the final RARP specimen: patients with extraprostatic (pT3/4) vs. organ-confined (pT2) disease. Additionally, the authors conducted subgroup analyses within both the extraprostatic and organ-confined disease groups to compare continence rates before and after the implementation of the new surgical technique, which included Full Functional-Length Urethra preservation (FFLU) and Neurovascular Structure-Adjacent Frozen-Section Examination (NeuroSAFE). Multivariable logistic regression models addressing long-term continence were used. RESULTS: Overall, the authors identified 201 study patients of whom 75 (37 %) exhibited extraprostatic and 126 (63 %) organ-confined disease. There was no significant difference in long-term continence rates between patients with extraprostatic and organ-confined disease (77 vs. 83 %; p = 0.3). Following the implementation of FFLU+ NeuroSAFE, there was an overall improvement in continence from 67 % to 89 % (Δ = 22 %; p < 0.001). No difference in the magnitude of improved continence rates between extraprostatic vs. organ-confined disease was observed (Δ = 22 % vs. Δ = 20 %). In multivariable logistic regression models, no difference between extraprostatic vs. organ-confined disease in long-term continence was observed (Odds Ratio: 0.91; p = 0.85). CONCLUSION: In this tertiary-based institutional study, patients with extraprostatic and organ-confined prostate cancer exhibited comparable long-term continence rates.

Prognostic Significance of Pathologic Lymph Node Invasion in Metastatic Renal Cell Carcinoma in the Immunotherapy Era.

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.

Patient and tumor characteristics of histological subtypes of renal cell carcinoma and its risk of upstaging to ≥pT3.

OBJECTIVE: To explore how histological subtypes impact upstaging to nonorgan confined renal cell carcinoma (≥pT3 RCC) in patients treated with partial/radical nephrectomy for cT1-2 RCC. MATERIALS AND METHODS: We relied on an institutional tertiary-care database to identify RCC patients treated with partial/radical nephrectomy between January 2002 and December 2021. Patients were stratified according to histological subtype of RCC. Upstaging was defined as any cT1-2 tumor classified as ≥pT3 at final pathology. Uni- and multivariable logistic regression models were fitted to predict upstaging. RESULTS: Of overall 1,020 surgically treated RCC patients, 743 harbored clear-cell (72.8%) vs. 193 (18.9%) papillary vs. 49 (4.8%) chromophobe vs. each 4 (0.4%) collecting duct and sarcomatoid vs. 27 (2.6%) other/mixed pathology of RCC. Median tumor size ranged from 3.0 cm (mixed RCC) to 7.7 cm (sarcomatoid RCC). In total, upstaging rate to ≥pT3 was 22% and ranged from 6.1% (chromophobe RCC) to 75% (collecting duct RCC). In univariable logistic regression models, chromophobe and papillary histological subtypes were significantly associated with lower upstaging of all cT1-2 RCC tumors. After controlling for patient and tumor characteristics in multivariable logistic regression models, papillary RCC independently lowers the risk of upstaging, even in sensitivity analyses for cT1 RCC only. CONCLUSION: Important differences between histological subtypes of RCC exist regarding characteristics such as stage and tumor size at presentation, as well as upstaging to ≥pT3 at final pathology. Specifically, papillary RCC is significantly associated with lower chance of upstaging even after controlling for confounding parameters. The study is limited by missing central pathological/radiographic review and lack of survival analyses.

In-Hospital Venous Thromboembolism and Pulmonary Embolism After Major Urologic Cancer Surgery.

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.

Differences in future life expectancy of testicular germ-cell tumor patients vs. age-matched male population-based controls.

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.

Regional differences in stage distribution and rates of treatment for adrenocortical carcinoma across United States SEER registries.

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.

Regional differences in penile cancer patient characteristics and treatment rates across the United States.

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.