Defining the optimal target-to-background ratio to identify positive lymph nodes in prostate cancer patients undergoing robot-assisted [99mTc]Tc-PSMA radioguided surgery: updated results and ad interim analyses of a prospective phase II study.

INTRODUCTION: Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown. MATERIALS & METHODS: Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([99mTc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed. RESULTS: Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients. CONCLUSIONS: PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios.

The immune-related adverse events paradox in locally advanced or metastatic urothelial cancer after atezolizumab immunotherapy: analysis of individual patient data from IMvigor210 and IMvigor211 trials.

OBJECTIVE: To investigate the association between immune-related adverse events (irAEs) and oncological outcomes in patients with advanced urothelial cancer receiving immune checkpoint inhibitors (ICIs), and whether the administration of systemic corticosteroids diminishes therapeutic impact. PATIENTS AND METHODS: The association between irAEs occurrence and clinical progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) was tested by means of multivariable Cox or competing-risks regression, when appropriate. Patients experiencing irAEs were further stratified based on systemic corticosteroids administration. A sensitivity analysis was conducted by repeating all the analyses with median time to irAE as landmark point. RESULTS: We relied on individual participant data from two prospective trials for advanced urothelial cancer: IMvigor210 and IMvigor211. A total of 896 patients who received atezolizumab for locally advanced or metastatic urothelial cancer were considered. Overall, irAEs were recorded in 195 patients and the median time to irAEs was 64 days. On multivariable analysis, irAEs were inversely associated with the risk of disease progression (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.40-0.61; P < 0.001), overall mortality (HR 0.51, 95% CI 0.41-0.64; P < 0.001), and cancer-specific mortality (subdistributional HR [sHR] 0.55, 95% CI 0.45-0.72; P < 0.001). Moreover, our results did not refute the supposition that the administration of systemic corticosteroids does not impact oncological outcomes (PFS: HR 0.92, 95% CI 0.62-1.34, P = 0.629; OS: HR 0.86, 95% CI 0.51-1.64, P = 0.613; CSS: sHR 0.90, 95% CI 0.60-1.36, P = 0.630). The sensitivity analysis confirmed our findings. CONCLUSIONS: The development of irAEs while receiving atezolizumab treatment was associated with improved oncological outcomes, namely overall and cancer-specific mortality, and PFS. These findings seem to not be substantially affected by administration of systemic corticosteroids.

Use of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) PET/CT for lymph node assessment before radical cystectomy in bladder cancer patients.

OBJECTIVE: To assess the diagnostic performance of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomograpy (PET)/computed tomography (CT) in nodal staging before radical cystectomy (RC) and pelvic lymph node dissection (PLND) for bladder cancer (BCa). MATERIALS AND METHODS: This analysis was based on a cohort of 199 BCa patients undergoing RC and bilateral PLND between 2015 and 2022. Neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) was administered after oncological evaluation. All patients received preoperative 18F-FDG PET/CT to assess extravesical disease. Point estimates for true negative, false negative, false positive, true positive, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of conventional imaging and PET/CT were calculated. Subgroup analysis in patients receiving neoadjuvant treatment was performed. RESULTS: At preoperative evaluation, 30 patients (15.1%) had 48 suspicious nodal spots on 18F-FDG PET/CT. At RC and bilateral PLND, a total of 4871 lymph nodes (LNs) were removed with 237 node metastases corresponding to 126 different regions. Pathological node metastases were found in 17/30 (57%) vs 39/169 patients (23%) with suspicious vs negative preoperative 18F-FDG PET/CT, respectively (sensitivity = 0.30, specificity = 0.91, PPV = 0.57, NPV = 0.77, accuracy = 0.74). On per-region analysis including 1367 nodal regions, LN involvement was found in 19/48 (39%) vs 105/1319 (8%) suspicious vs negative regions at PET/CT, respectively (sensitivity = 0.15, specificity = 0.98, PPV = 0.40, NPV = 0.92, ACC = 0.90). Similar results were observed for patients receiving NAC (n = 44, 32.1%) and NAI (n = 93, 67.9% [per-patient: sensitivity = 0.36, specificity = 0.91, PPV = 0.59, NPV = 0.80, accuracy = 0.77; per-region: sensitivity = 0.12, specificity = 0.98, PPV = 0.32, NPV = 0.93, ACC = 0.91]). Study limitations include its retrospective design and limited patient numbers. CONCLUSIONS: In eight out of 10 patients with negative preoperative 18F-FDG PET/CT, pN0 disease was confirmed at final pathology. No differences were found based on NAC vs NAI treatment. These findings suggest that 18F-FDG PET/CT could play a role in the preoperative evaluation of nodal metastases in BCa patients, although its cost-effectiveness is uncertain.

Transitioning from Da Vinci Si to Xi: assessing surgical outcomes at a high-volume robotic center.

PURPOSE: In the emerging field of robotics, only few studies investigated the transition between different robotic platforms in terms of surgical outcomes. We aimed at assessing surgical outcomes of patients receiving robot-assisted radical prostatectomy (RARP) and robot-assisted partial nephrectomy (RAPN) at a high-volume robotic center during the transition from Si to Xi Da Vinci surgical systems. METHODS: We analyzed data of 1884 patients undergoing RARP (n = 1437, 76%) and RAPN (n = 447, 24%) at OLV hospital (Aalst, Belgium) between 2011 and 2021. For both procedures, we assessed operative time, estimated blood loss, length of stay, and positive surgical margins. For RARP, we investigated length of catheterization and PSA persistence after surgery, whereas warm ischemia time, clampless surgery, and acute kidney injury (AKI) were assessed for RAPN. Multivariable analyses (MVA) investigated the association between robotic platform (Si vs. Xi) and surgical outcomes after adjustment for patient- and tumor-related factors. RESULTS: A total of 975 (68%) and 462 (32%) patients underwent RARP performed with the Si vs. Xi surgical system, respectively. Baseline characteristics did not differ between the groups. On MVA, we did not find evidence of a difference between the groups with respect to operative time (estimate: 1.07) or estimated blood loss (estimate: 32.39; both p > 0.05). Median (interquartile range [IQR]) length of stay was 6 (3, 6) and 4 (3, 5) days in the Si vs. Xi group, respectively (p < 0.0001). On MVA, men treated with the Xi vs. Si robot had lower odds of PSM (Odds ratio [OR]: 0.58; p = 0.014). A total of 184 (41%) and 263 (59%) patients received RAPN with the Si and Xi robotic system, respectively. Baseline characteristics, including demographics, functional data, and tumor-related features did not differ between the groups. On MVA, operative time was longer in the Xi vs. Si group (estimate: 30.54; p = 0.006). Patients treated with the Xi vs. Si system had higher probability of undergoing a clampless procedure (OR: 2.56; p = 0.001), whereas the risk of AKI did not differ between the groups (OR: 1.25; p = 0.4). On MVA, patients operated with the Xi robot had shorter length of stay as compared to the Si group (estimate: - 0.86; p = 0.003), whereas we did not find evidence of an association between robotic system and PSM (OR: 1.55; p = 0.3). CONCLUSION: We found that the Xi robot allowed for improvements in peri-operative outcomes as compared to the Si platform, with lower rate of positive margins for RARP and higher rate of off-clamp procedures for RAPN. Hospital stay was also shorter for patients operated with the Xi vs. Si robot, especially after robot-assisted partial nephrectomy. Awaiting future investigations-in particular, cost analyses-these results have important implications for patients, surgeons, and healthcare policymakers.

Epidemiology of Unconventional Histological Subtypes of Urethral Cancer.

INTRODUCTION: The aim of the study was to examine cancer-specific mortality (CSM) of unconventional urethral cancers. METHODS: Within the SEER (2004-2016) database, we analyzed CSM of 165 patients with unconventional urethral-cancer histology. Kaplan-Meier plots were used to test the effect of unconventional histologies in urethral cancer on CSM. RESULTS: Of 165 eligible patients, the Mullerian type accounted for 55 (33.3%) versus melanocytic (26.7%) versus neuroendocrine 25 (15.2%) versus lymphoma 22 (13.3%) versus mesenchymal/sarcoma 15 (9.1%) versus spindle cell 4 (2.1%) patients. Median age at diagnosis was 81 years in spindle cell, 75 in melanocytic, 74 in neuroendocrine and mesenchymal/sarcoma, 67 in lymphoma, and 62 years Mullerian type (p < 0.001). Of all, 116 (70.3%) were female. The Mullerian type exhibited the highest female ratio (96.4%) versus the lowest female ratio in neuroendocrine (24.0%). The Mullerian type was most frequent in African-American females. In Caucasian females, the melanocytic type was most frequent (49.1%). In African-American (38.9%) and Caucasian males (33.3%), neuroendocrine histology was most frequent. Three-year CSM was, respectively, 27.5%, 23.1% 22.3%, 20.5%, and 16.1% for melanocytic, mesenchymal/sarcoma, Mullerian type, neuroendocrine, and lymphoma histology. Median cancer-specific survival was 106 versus 10 months for combined nonmetastatic versus metastatic nonconventional histologies. CONCLUSION: Important age, sex, racial/ethnic group distribution, and survival differences exist between each unconventional urethral-cancer histological subtypes.

Different approaches for bladder neck dissection during robot-assisted radical prostatectomy: the Aalst technique.

INTRODUCTION: Bladder neck dissection is one of the most delicate surgical steps of robotic-assisted radical prostatectomy (RARP) [1, 2], and it may affect surgical margins rate and functional outcomes [3, 4]. Given the relationship between outcomes and surgical experience [5-7], it is crucial to implement a step-by-step approach for each surgical step of the procedure, especially in the most challenging part of the intervention. In this video compilation, we described the techniques for bladder neck dissection utilized at OLV Hospital (Aalst, Belgium). SURGICAL TECHNIQUE: We illustrated five different techniques for bladder neck dissection during RARP. The anterior technique tackles the bladder neck from above until the urethral catheter is visualized, and then the dissection is completed posteriorly. The lateral and postero-lateral approaches involve the identification of a weakness point at the prostate-vesical junction and aim to develop the posterior plane - virtually until the seminal vesicles - prior to the opening of the urethra anteriorly. Finally, we described our techniques for bladder neck dissection in more challenging cases such as in patients with bulky middle lobes and prior surgery for benign prostatic hyperplasia. All approaches follow anatomic landmarks to minimize positive surgical margins and aim to preserve the bladder neck in order to promote optimal functional recovery. All procedures were performed with DaVinci robotic platforms using a 3-instruments configuration (scissors, fenestrated bipolar, and needle driver). As standard protocol at our Institution, urinary catheter was removed on postoperative day two [8]. CONCLUSIONS: Five different approaches for bladder neck dissection during RARP were described in this video compilation. We believe that the technical details provided here might be of help for clinicians who are starting their practice with this surgical intervention.

Survival rates with external beam radiation therapy in newly diagnosed elderly metastatic prostate cancer patients.

BACKGROUND: The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy. METHODS: We relied on Surveillance, Epidemiology and End Results (2004-2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan-Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM). RESULTS: Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages. CONCLUSIONS: In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients.

Temporal trends, tumor characteristics and stage-specific survival in penile non-squamous cell carcinoma vs. squamous cell carcinoma.

PURPOSE: To compare Cancer-specific mortality (CSM) in patients with Squamous cell carcinoma (SCC) vs. non-SCC penile cancer, since survival outcomes may differ between histological subtypes. METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2016), penile cancer patients of all stages were identified. Temporal trend analyses, cumulative incidence and Kaplan-Meier plots, multivariable Cox regression and Fine and Gray competing-risks regression analyses tested for CSM differences between non-SCC vs. SCC penile cancer patients. RESULTS: Of 4,120 eligible penile cancer patients, 123 (3%) harbored non-SCC vs. 4,027 (97%) SCC. Of all non-SCC patients, 51 (41%) harbored melanomas, 42 (34%) basal cell carcinomas, 10 (8%) adenocarcinomas, eight (6.5%) skin appendage malignancies, six (5%) epithelial cell neoplasms, two (1.5%) neuroendocrine tumors, two (1.5%) lymphomas, two (1.5%) sarcomas. Stage at presentation differed between non-SCC vs. SCC. In temporal trend analyses, non-SCC diagnoses neither decreased nor increased over time (p > 0.05). After stratification according to localized, locally advanced, and metastatic stage, no CSM differences were observed between non-SCC vs. SCC, with 5-year survival rates of 11 vs 11% (p = 0.9) for localized, 33 vs. 37% (p = 0.4) for locally advanced, and 1-year survival rates of 37 vs. 53% (p = 0.9) for metastatic penile cancer, respectively. After propensity score matching for patient and tumor characteristics and additional multivariable adjustment, no CSM differences between non-SCC vs. SCC were observed. CONCLUSION: Non-SCC penile cancer is rare. Although exceptions exist, on average, non-SCC penile cancer has comparable CSM as SCC penile cancer patients, after stratification for localized, locally invasive, and metastatic disease.

Clinical Outcomes and Adverse Events after First-Line Treatment in Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-Analysis.

PURPOSE: Four recent first-line clinical trials leveraging immune-oncology agents demonstrated an overall survival (OS) benefit relative to sunitinib. We aimed to provide formal comparisons among immune-oncology combinations in terms of OS, progression-free survival (PFS), objective response rates and treatment-related adverse events (AEs). MATERIALS AND METHODS: PubMed® database was searched for studies indexed from January 1, 2016 through March 6, 2021. Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included: CheckMate 214 (nivolumab plus ipilimumab [N+I]), KEYNOTE-426 (pembrolizumab plus axitinib [P+A]), CheckMate 9ER (nivolumab plus cabozantinib [N+C]) and KEYNOTE-581 (lenvatinib plus permbrolizumab [L+P]). OS represented the primary outcome. PFS, objective response rate and AEs represented secondary outcomes. RESULTS: Overall, 3,320 patients were included. Regarding OS, N+C ranked first, followed by L+P, P+A and N+I. Regarding PFS and objective response rate, L+P ranked first, followed by N+C, P+A and N+I. Finally, N+I ranked first with respect to lowest grade 3+ AEs, followed by P+A, N+C and L+P. Differences in followup duration, risk grouping and nephrectomy rates distinguish the studies. CONCLUSIONS: N+C may provide the most favorable OS, L+P the most favorable PFS and ORRs, and N+I the lowest toxicity. Population differences may potentially undermine the generalizability and the robustness of findings of metastatic renal cell carcinoma.

The impact of race/ethnicity on upstaging and/or upgrading rates among intermediate risk prostate cancer patients treated with radical prostatectomy.

BACKGROUND: Race/ethnicity may predispose to less favorable prostate cancer characteristics in intermediate risk prostate cancer (IR PCa) patients. We tested this hypothesis in a subgroup of IR PCa patients treated with radical prostatectomy (RP). METHODS: We relied on the Surveillance, Epidemiology and End Results 2004-2016. The effect of race/ethnicity was tested in univariable and multivariable logistic regression analyses predicting upstaging (pT3+/pN1) and/or upgrading (Gleason Grade Group [GGG] 4-5) at RP. RESULTS: Of 20,391 IR PCa patients, 15,050 (73.8%) were Caucasian, 2857 (14.0%) African-American, 1632 (8.0%) Hispanic/Latino and 852 (4.2%) Asian. Asian patients exhibited highest age (64 year), highest PSA (6.8 ng/ml) and highest rate of GGG3 (31.9%). African-Americans exhibited the highest percentage of positive cores at biopsy (41.7%) and the highest proportion of NCCN unfavorable risk group membership (54.6%). Conversely, Caucasians exhibited the highest proportion of cT2 stage (35.6%). In univariable analyses, Hispanic/Latinos exhibited the highest rates of upstaging/upgrading among all race/ethnicities, in both favorable and unfavorable groups, followed by Asians, Caucasians and African-Americans in that order. In multivariable analyses, Hispanic/Latino race/ethnicity represented an independent predictor of higher upstaging and/or upgrading in favorable IR PCa (odds ratio [OR] 1.27, p < 0.01), while African-American race/ethnicity represented an independent predictor of lower upstaging and/or upgrading in unfavorable IR PCa (OR 0.79, p < 0.001). CONCLUSION: Race/ethnicity predisposes to differences in clinical, as well as in pathological characteristics in IR PCa patients. Specifically, even after full statistical adjustment, Hispanic/Latinos are at higher and African-Americans are at lower risk of upstaging and/or upgrading.

The effect of primary urological cancers on survival in men with secondary prostate cancer.

BACKGROUND: To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa). METHODS: Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses. RESULTS: We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis. CONCLUSIONS: After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.

Increasing rates of NCCN high and very high-risk prostate cancer versus number of prostate biopsy cores.

BACKGROUND: Recently, an increase in the rates of high-risk prostate cancer (PCa) was reported. We tested whether the rates of and low, intermediate, high and very high-risk PCa changed over time. We also tested whether the number of prostate biopsy cores contributed to changes rates over time. METHODS: Within the Surveillance, Epidemiology and End Results (SEER) database (2010-2015), annual rates of low, intermediate, high-risk according to traditional National Comprehensive Cancer Network (NCCN) and high versus very high-risk PCa according to Johns Hopkins classification were tabulated without and with adjustment for the number of prostate biopsy cores. RESULTS: In 119,574 eligible prostate cancer patients, the rates of NCCN low, intermediate, and high-risk PCa were, respectively, 29.7%, 47.8%, and 22.5%. Of high-risk patients, 39.6% and 60.4% fulfilled high and very high-risk criteria. Without adjustment for number of prostate biopsy cores, the estimated annual percentage changes (EAPC) for low, intermediate, high and very high-risk were respectively -5.5% (32.4%-24.9%, p < .01), +0.5% (47.6%-48.4%, p = .09), +4.1% (8.2%-9.9%, p < .01), and +8.9% (11.8%-16.9%, p < .01), between 2010 and 2015. After adjustment for number of prostate biopsy cores, differences in rates over time disappeared and ranged from 29.8%-29.7% for low risk, 47.9%-47.9% for intermediate risk, 8.9%-9.0% for high-risk, and 13.6%-13.6% for very high-risk PCa (all p > .05). CONCLUSIONS: The rates of high and very high-risk PCa are strongly associated with the number of prostate biopsy cores, that in turn may be driven by broader use magnetic resonance imaging (MRI).

The effect of lymph node dissection on cancer-specific survival in salvage radical prostatectomy patients.

BACKGROUND: We hypothesized that lymph node dissection (LND) at salvage radical prostatectomy may be associated with lower cancer-specific mortality (CSM) and we tested this hypothesis. METHODS: We relied on surveillance, epidemiology, and end results (2004-2016) to identify all salvage radical prostatectomy patients. Categorical, as well as univariate and multivariate Cox regression models tested the effect of LND (LND performed vs. not), as well as at its extent (log-transformed lymph node count) on CSM. RESULTS: Of 427 salvage radical prostatectomy patients, 120 (28.1%) underwent LND with a median lymph node count of 6 (interquartile range [IQR], 3-11). According to LND status, no significant or clinically meaningful differences were recorded in PSA at diagnosis, stage and biopsy Gleason score at diagnosis, except for age at prostate cancer diagnosis (LND performed 63 vs. 68 years LND not performed, p < .001). LND status (performed) was an independent predictor of lower CSM (hazard ratio [HR] 0.47; p = .03). Similarly, lymph node count (log transformed) also independently predicted lower CSM (HR: 0.60; p = .01). After the 7th removed lymph node, the effect of CSM became marginal. The effect of N-stage on CSM could not be tested due to insufficient number of observations. CONCLUSIONS: Salvage radical prostatectomy is rarely performed and LND at salvage radical prostatectomy is performed in a minority of patients. However, LND at salvage radical prostatectomy is associated with lower CSM. Moreover, LND extent also exerts a protective effect on CSM. These observations should be considered in salvage radical prostatectomy candidates.

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

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

Incidence rates and contemporary trends in primary urethral cancer.

PURPOSE: We assessed contemporary incidence rates and trends of primary urethral cancer. METHODS: We identified urethral cancer patients within Surveillance, Epidemiology and End Results registry (SEER, 2004-2016). Age-standardized incidence rates per 1,000,000 (ASR) were calculated. Log linear regression analyses were used to compute average annual percent change (AAPC). RESULTS: From 2004 to 2016, 1907 patients with urethral cancer were diagnosed (ASR 1.69; AAPC: -0.98%, p = 0.3). ASR rates were higher in males than in females (2.70 vs. 0.55), respectively and did not change over the time (both p = 0.3). Highest incidence rates were recorded in respectively ≥75 (0.77), 55-74 (0.71) and ≤54 (0.19) years of age categories, in that order. African Americans exhibited highest incidence rate (3.33) followed by Caucasians (1.72), other race groups (1.57) and Hispanics (1.57), in that order. A significant decrease occurred over time in Hispanics, but not in other race groups. In African Americans, male and female sex-stratified incidence rates were higher than in any other race group. Urothelial histological subtype exhibited highest incidence rate (0.92), followed by squamous cell carcinoma (0.41), adenocarcinoma (0.29) and other histologies (0.20). In stage stratified analyses, T1N0M0 stage exhibited highest incidence rate. However, it decreased over time (-3.00%, p = 0.02) in favor of T1-4N1-2M0 stage (+ 2.11%, p = 0.02). CONCLUSION: Urethral cancer is rare. Its incidence rates are highest in males, elderly patients, African Americans and in urothelial histological subtype. Most urethral cancer cases are T1N0M0, but over time, the incidence of T1N0M0 decreased in favor of T1-4N1-2M0.

Racial/Ethnic Disparities in Tumor Characteristics and Treatments in Favorable and Unfavorable Intermediate Risk Prostate Cancer.

PURPOSE: We hypothesized that differences in active treatment rates may exist according to race/ethnicity in favorable as well as unfavorable intermediate risk prostate cancer. MATERIALS AND METHODS: We relied on the Surveillance, Epidemiology, and End Results 18 database 2010-2015. We stratified according to 3 racial/ethnic groups (White vs Black vs Hispanic) and prostate cancer baseline characteristics (prostate specific antigen, clinical T stage, Gleason group grading, percentage of biopsy cores). We tabulated active treatment rates (radical prostatectomy, external beam radiotherapy) without and with adjustment for baseline age and prostate cancer characteristics. RESULTS: Baseline prostate specific antigen, clinical T stage, Gleason grade and percentage of positive biopsy cores differed according to racial/ethnic groups in both favorable and unfavorable intermediate risk prostate cancer patients (all p <0.05). Similarly, radical prostatectomy and external beam radiotherapy rates differed according to race/ethnicity in both favorable and unfavorable intermediate risk prostate cancer patients. Radical prostatectomy and external beam radiotherapy rates respectively ranged from 31.7%-41.8% and 26.3%-31.0% in favorable intermediate risk cases and from 33.4%-43.9% and 30.9%-35.5% in unfavorable intermediate risk prostate cancer, across the 3 race/ethnicity groups (both p <0.05). The above heterogeneity in active treatment rates disappeared and marginal differences remained after adjustment for baseline age and prostate cancer characteristics. CONCLUSIONS: Interpretation of active treatment rates in favorable and unfavorable intermediate risk prostate cancer may be severely biased, unless detailed and systematic consideration or adjustment for baseline age and prostate cancer characteristic is enforced.

Sex- and Age-Related Differences in the Distribution of Metastases in Patients With Upper Urinary Tract Urothelial Carcinoma.

BACKGROUND: The distribution of metastatic sites in upper tract urothelial carcinoma (UTUC) is not well-known. Consequently, the effects of sex and age on the location of metastases is also unknown. This study sought to investigate age- and sex-related differences in the distribution of metastases in patients with UTUC. MATERIALS AND METHODS: Within the Nationwide Inpatient Sample database (2000-2015), we identified 1,340 patients with metastatic UTUC. Sites of metastasis were assessed according to age (≤63, 64-72, 73-79, and ≥80 years) and sex. Comparison was performed with trend and chi-square tests. RESULTS: Of 1,340 patients with metastatic UTUC, 790 (59.0%) were men (median age, 71 years) and 550 (41.0%) were women (median age, 74 years). The lung was the most common site of metastases in men and women (28.2% and 26.4%, respectively), followed by bone in men (22.3% vs 18.0% of women) and liver in women (24.4% vs 20.5% of men). Increasing age was associated with decreasing rates of brain metastasis in men (from 6.5% to 2.9%; P=.03) and women (from 5.9% to 0.7%; P=.01). Moreover, increasing age in women, but not in men, was associated with decreasing rates of lung (from 33.3% to 24.3%; P=.02), lymph node (from 28.9% to 15.8%; P=.01), and bone metastases (from 22.2% to 10.5%; P=.02). Finally, rates of metastases in multiple organs did not vary with age or sex (65.2% in men vs 66.5% in women). CONCLUSIONS: Lung, bone, and liver metastases are the most common metastatic sites in both sexes. However, the distribution of metastases varies according to sex and age. These observations apply to everyday clinical practice and may be used, for example, to advocate for universal bone imaging in patients with UTUC. Moreover, our findings may also be used for design considerations of randomized trials.

Survival advantage of Asian metastatic prostate cancer patients treated with external beam radiotherapy over other races/ethnicities.

PURPOSE: To assess the effect of race/ethnicity in cancer-specific mortality (CSM) adjusted for other-cause mortality (OCM) in metastatic prostate cancer patients (mPCa) treated with external beam radiotherapy (EBRT) to the prostate. METHODS: We relied on the Surveillance, Epidemiology, and End Results (SEER) database to identify Caucasian, African-American, Hispanic/Latino and Asian mPCa patients treated by EBRT between 2004 and 2016. Cumulative incidence plots displayed CSM after adjustment for OCM according to race/ethnicity. Propensity score matching accounted for patient age, prostate-specific antigen, clinical T and N stages, Gleason Grade Groups and M1 substages. OCM adjusted multivariable analyses tested for differences in CSM in African-Americans, Hispanic/Latinos and Asians relative to Cauacasians. RESULTS: After 3:1 propensity score matching and OCM adjustment, Asians exhibited lower CSM at 60 and 120 months (48.2 and 60.0%, respectively) compared to Caucasians (66.7 and 79.4%, respectively, p < 0.001). In OCM adjusted multivariable analyses, Asian race/ethnicity was associated with lower CSM (HR 0.66, CI 0.52-0.83, p < 0.001). Conversely, African-American and Hispanic/Latino race/ethnicity did not affect CSM. OCM rates were comparable between examined races/ethnicities. CONCLUSION: In the setting of mPCa treated with EBRT, Asians exhibit lower CSM than Caucasians, African-Americans and Hispanic/Latinos. This observation may warrant consideration in prognostic stratification schemes for newly diagnosed mPCa patients.

Differences between rural and urban prostate cancer patients.

BACKGROUND: We hypothesized that the residency status (rural area [RA] vs urban clusters [UC] vs urban areas [UA]) affects stage and cancer-specific mortality (CSM) in contemporary newly diagnosed prostate cancer (PCa) patients of all stages, regardless of treatment. METHODS: Newly diagnosed PCa patients with available residency status were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Propensity-score (PS) matching, cumulative incidence plots, multivariate competing-risks regression (CRR) models were used. RESULTS: Of 531,468 PCa patients of all stages, 6653 (1.3%) resided in RA, 50,932 (9.6%) in UC and 473,883 (89.2%) in UA. No statistically significant or clinically meaningful differences in stage at presentation or CSM were recorded. Conversely, 10-year other cause-mortality (OCM) rates were 27.2% vs 23.7% vs 18.9% (p < 0.001) in RA vs UC vs UA patients, respectively. In CRR models, RA (subhazard ratio [SHR] 1.38; p < 0.001) and UC (SHR 1.18; p < 0.001) were independent predictors for higher OCM relative to UA. These differences remained statistically significant in fully PS-adjusted multivariate CRR models. CONCLUSION: RA, and to a lesser extent UC, PCa patients are at higher risk of OCM than UA patients. Higher OCM may indicate shorter life expectancy and should be considered in treatment decision making.

Comparison between 1973 and 2004/2016 World Health Organization grading in upper tract urothelial carcinoma treated with radical nephroureterectomy.

AIMS: The European Association of Urology guideline for upper tract urothelial carcinoma (UTUC) relies on two grading system: 1973 World Health Organization (WHO) and 2004/2016 WHO. No consensus has been made which classification should supersede the other and both are recommended in clinical practice. We hypothesized that one may be superior to the other. METHODS: Newly diagnosed non-metastatic UTUC patients treated with radical nephroureterectomy were abstracted from the Surveillance, Epidemiology, and End Results database (2010-2016). Kaplan-Meier plots and multivariable Cox regression models (CRMs) tested cancer-specific mortality (CSM), according to 1973 WHO (G1 vs. G2 vs. G3) or to 2004/2016 WHO (low-grade vs. high-grade) grading systems. Haegerty's C-index quantified accuracy. RESULTS: Of 4271 patients, according to 1973 WHO grading system, 134 (3.1%) were G1, 436 (10.2%) were G2 and 3701 (86.7%) were G3; while according to 2004/2016 WHO grading system, 508 (11.9%) were low grade vs 3763 (88.1%) high grade. In multivariable CRMs, high grade predicted higher CSM (Hazard ratio: 1.70, p < 0.001). Conversely, neither G2 (p = 0.8) nor G3 (p = 0.1) were independent predictors of worse survival. The multivariable models without consideration of either grading system were 74% accurate in predicting 5-year CSM. Accuracy increased to 76% after either addition of the 1973 WHO or 2004/2016 WHO grade. CONCLUSIONS: From a statistical standpoint, either 1973 WHO or 2004/2016 WHO grading system improves the accuracy of CSM prediction to the same extent. In consequence, other considerations such as intra- and interobserver variability may represent additional metrics to consider in deciding which grading system is better.