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Background Prostate cancer (PCa) staging is crucial in clinical decision making and treatment assignment. Objective To develop a predictive tool that is capable of predicting the probability of metastases at initial PCa diagnosis. Design, setting, and participants Within the Surveillance, Epidemiology, and End Results database (2010–2014), we identified patients with newly diagnosed PCa and available clinical tumor stage, prostatic-specific antigen value (PSA), and Gleason grade group (GGG), and with or without metastases. Outcome measurements and statistical analysis We relied on PSA, clinical tumor stages, and GGG to discriminate between M1 and M0 patients. Patients were randomly divided according to the registry of origin between development (n = 102 469) and validation (n = 98 755) cohorts. Logistic regression modeling coefficients were used to devise a lookup table to discriminate between M0 and M1 stages. Receiver operating characteristic-derived area under the curve was tested for model accuracy, within the validation cohort. A total of 2000 bootstrap resamples were applied to 95% confidence intervals (CIs). Decision curve analysis (DCA) and calibration plots were used to test the performance of the lookup table. Results and limitations Of 201 224 patients, 3.5% harbored metastatic PCa (mPCa). PSA >40 ng/ml, GGG5, and GGG4, in that order, represented the strongest predictors of mPCa. Overall, PSA, clinical tumor stage, and GGG were 94.3% (95% CI: 94.2–94.3%) accurate in predicting the probability of mPCa, in the external validation cohort. Up to 39.4% probability of mPCa, the model demonstrated accurate predictions in the calibration plot. In DCA, a net benefit was recorded up to a threshold probability of approximately 54%. Conclusions The proposed lookup table for the prediction of the probability of mPCa may represent a useful clinical tool based on its high accuracy, excellent calibration, and robust nature of predictions. Patient summary Our study provides a highly accurate lookup table for the prediction of the probability of metastatic prostate cancer patients. This clinical tool can be useful in staging decisions.

Backround: Accurate life expectancy estimation is crucial in clinical decision-making including management and treatment of clinically localized prostate cancer (PCa). Objective: We hypothesized that Social Security Administration (SSA) life tables’ derived survival estimates closely follow observed survival of PCa patients. To test this relationship, we examined 10-yr overall survival rates in patients with clinically localized PCa and compared it with survival estimates derived from the SSA life tables. Patients and methods: Within the Surveillance, Epidemiology, and End Results database (2004), we identified patients aged >50– < 90 yr. Follow-up was at least 10 yr for patients who did not die of disease or other causes. Outcome measurements and statistical analysis: Monte Carlo method was used to define individual survival in years, according to the SSA life tables (2004–2014). Subsequently, SSA life tables’ predicted survival was compared with observed survival rates in Kaplan-Meier analyses. Subgroup analyses were stratified according to treatment type and D'Amico risk classification. Results and limitations: Overall, 39 191 patients with localized PCa were identified. At 10-yr follow-up, the SSA life tables’ predicted survival was 69.5% versus 73.1% according to the observed rate (p < 0.0001). The largest differences between estimated versus observed survival rates were recorded for D'Amico low-risk PCa (8.0%), brachytherapy (9.1%), and radical prostatectomy (8.6%) patients. Conversely, the smallest differences were recorded for external beam radiotherapy (1.7%) and unknown treatment type (1.6%) patients. Conclusions: Overall, SSA life tables’ predicted life expectancy closely approximate observed overall survival rates. However, SSA life tables’ predicted rates underestimate by as much as 9.1% the survival in brachytherapy patients, as well as in D'Amico low-risk and radical prostatectomy patients. In these patient categories, an adjustment for the degree of underestimation might be required when counseling is provided in clinical practice. Patient summary: Social Security Administration (SSA) life tables’ predicted life expectancy closely approximate observed overall survival rates. However, SSA life tables’ predicted rates underestimate by as much as 9.1% the survival in brachytherapy patients, as well as in D'Amico low-risk and radical prostatectomy patients. Social Security Administration life tables’ predicted life expectancy closely approximate observed survival rates. However, life tables’ predicted rates underestimate by as much as 9.1% the overall survival in brachytherapy patients as well as in D'Amico low-risk and radical prostatectomy patients.

Background: Patients with organ confined muscle-invasive bladder cancer (MIBC) who are candidates for radical cystectomy (RC) should receive neoadjuvant chemotherapy (CHT). However, the most contemporary CHT use rates indicate low adherence to these guidelines. We tested contemporary neoadjuvant CHT rates and associated cancer-specific mortality (CSM) and overall mortality (OM) in pT2N0 MIBC patients treated with RC. Materials and methods: Within the SEER database (2004–2015), we identified patients with pT2N0 MIBC patients who underwent RC. CHT administration rates were evaluated using estimated annual percentage changes (EAPCs) analyses. After inverse probability of treatment weighting (IPTW), Kaplan–Meier (KM) analyses and Cox regression models (CRMs) were used to test the effect of CHT vs no CHT on survival. Landmark analyses tested for immortal time bias. Results: Of 3978 RC patients, 38.2% of patients received CHT. Between 2004 and 2015, CHT rates increased from 15.9% to 66.2% (EAPC: +14.2%; p < 0.001). IPTW-adjusted KM showed 10-year CSM-free survival rates of 78.9% for CHT vs 76.7% for no CHT patients (p = 0.6). Similarly, IPTW-adjusted KM showed 10-year OM-free survival rates of 54.6% for CHT vs 57.9% for no CHT patients (p = 0.8). In IPTW-adjusted MCRMs, CHT was not significantly associated with lower CSM (HR 0.97, CI 0.82–1.14; p = 0.7) or OM (HR 1.02, CI 0.90–1.16; p = 0.7). Virtually the same CSM and OM rates were recorded after landmark analyses. Conclusions: CHT use in pT2N0 MIBC RC patients sharply increased over the study span. However, neoadjuvant CHT was not associated with better survival in this patient group.

Cytoreductive radical prostatectomy (CRP) may offer a survival advantage, according to several retrospective analyses. However, few data are available regarding the morbidity of radical prostatectomy in the metastatic setting. We addressed intra- and postoperative complications of CRP relative to radical prostatectomy for nonmetastatic prostate cancer (nmRP). Within the National Inpatient Sample database (2008–2013), we identified patients who underwent CRP versus nmRP. Propensity score matching to reduce the effect of inherent differences between CRP and nmRP patients, multivariable logistic regression models, Poisson regression models, and linear regression models were used. Of 76 378 patients, 1.2% (n = 953) underwent CRP. CRP resulted in higher rates of overall (odds ratio [OR]: 1.34, p = 0.01), intraoperative (OR: 2.61, p = 0.005), and miscellaneous surgical complications (OR: 1.69, p = 0.02). Moreover, CRP was associated with longer stay (OR: 1.07, p = 0.01) and higher total hospital charges ($810 more per surgery, p = 0.0004). Intra- and postoperative complications associated with CRP are higher than those of nmRP. Similarly, an increase in total hospital charges is associated with CRP. Nonetheless, CRP complication profile validates its safety and feasibility. Patient summary: In this population-based study, we recorded higher intra- and postoperative complications rates for CRP versus nmRP. Nonetheless, CRP complication rates appear manageable but require explicit discussion at counseling. Perioperative complications associated with cytoreductive radical prostatectomy are moderately higher than those of radical prostatectomy in nonmetastatic prostate cancer patients. Similarly, total hospital charges are marginally higher. Nonetheless, the complication profile of cytoreductive radical prostatectomy validates its safety and feasibility in highly selected patients.

Introduction: Very few population-based assessments of delirium have been performed to date. These have not assessed the implications of delirium after major surgical oncology procedures (MSOPs). We examined the temporal trends of delirium following 10 MSOPs, as well as patient and hospital delirium risk factors. Finally, we examined the effect of delirium on length of stay, in-hospital mortality, and hospital charges. Methods: We retrospectively identified patients who underwent prostatectomy, colectomy, cystectomy, mastectomy, gastrectomy, hysterectomy, nephrectomy, oophorectomy, lung resection, or pancreatectomy within the Nationwide Inpatient Sample (2003‒2013). We yielded a weighted estimate of 3 431 632 patients. Multivariable logistic regression (MLR) analyses identified the determinants of postoperative delirium, as well as the effect of delirium on length of stay, in-hospital mortality, and hospital charges. Results: Between 2003 and 2013, annual delirium rate increased from 0.7 to 1.2% (+6.0%; p

Background: The National Comprehensive Cancer Network (NCCN) guidelines provide recommendations for staging of prostate cancer patients in the objective regarding presence of locoregional lymph node metastases (LNM) and bone metastases. We tested the performance characteristics of these recommendations in a community setting. Methods: Within the Surveillance, Epidemiology, and End Results database (2004–2014), we identified patients with available Gleason, clinical stage and prostatic specific antigen. Performance characteristics endpoints consisted of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NVP), overall accuracy and the number needed to image (NNI). Results: Totally, 191,308 patients were assessable for the validation of the LNM staging recommendations. Sensitivity ranged from 80.6 to 86.3%, specificity from 74.7 to 79.3%, PPV from 7.8 to 8.0%, overall accuracy from 75.0 to 79.3% and NPV was 99.5%. The respective NNI values were 12.5 and 12.8. 197,408 patients were assessable for the validation of bone scan recommendations. These recommendations resulted in 90.8% sensitivity, 76.3% specificity, PPV of 5.7%, NPV of 99.8% and overall accuracy of 76.5%. The NNI was 17.5. Conclusion: The NCCN recommendations for locoregional LNM miss few patients with clinical LNM (0.3–0.4%) and provide a virtually perfect NPV of 99.5%. Also, the recommendations for bone scan miss a marginal number of patients with established bone metastases (0.14%) and yield a virtually perfect NPV of 99.8%.

Enhanced recovery after surgery protocols (ERAS) have been developed and implemented as of 2001. However, no previous analyses targeted length of stay (LOS) changes over time after major surgical oncological procedures (MSOPs).Between 2003 and 2013, we retrospectively identified patients, who underwent prostatectomy, colectomy, cystectomy, mastectomy, gastrectomy, hysterectomy, nephrectomy, oophorectomy, lung resection or pancreatectomy within the Nationwide Inpatient Sample. A total of 3 431 602 assessable patients were identified. We examined temporal trends of LOS after ten MSOPs, as well as LOS determinants and the impact of LOS on total hospital charges (THCGs). Univariable and multivariable linear, log-linear, logistic (MLR) and Poisson regression (MPR) analyses were used.Mean and median LOS were respectively 6 and 4 days (IQR 2-7). During the study span, LOS decreased [Estimated annual percentage change (EAPC): -1.89%, p = 0.0002]. Of the ten examined MSOPs, nine showed a decrease that ranged from -4.47% in prostatectomy to -0.7% in mastectomy. Conversely, no decrease in LOS was recorded for colectomy (EAPC:+0.37, p = 0.015). In MPR analyses, robotic [Relative risk (RR):0.68, p = 0.0003] and laparoscopic (RR: 0.90, p 0.0001) surgical approaches were associated with shorter LOS. LOS was directly related to THCGs.Since the implementation of ERAS protocols, LOS has decreased for nine out of ten MSOPs in a significant fashion. Although these gains may appear marginal on an annual basis, their cumulative effect, over the study span, ranges for 7.7%-49.2%, which can hardly be interpreted as marginal. LOS decrease directly translates in THCGs savings.

BACKGROUND To test whether local treatment (LT), namely radical prostatectomy (RP) or brachytherapy (BT) still confers a survival benefit versus no local treatment (NLT), when adjusted for baseline PSA (bPSA). To further examine whether the effect of LT might be modulated according to bPSA and M1 substages. METHODS Of 13 906 mPCa patients within the SEER (2004-2014), 375 underwent RP, 175 BT, and 13 356 NLT. Multivariable competing risks regression (MVA CRR) analyses after 1:2 propensity score matching assessed the impact of LT versus NLT on cancer specific mortality (CSM). Interaction analyses tested the association between treatment type and bPSA within different M1 substages. RESULTS MVA CRR analyses revealed lower CSM rates for LT (RP [HR: 0.55, CI: 0.44-0.70, P

Purpose: To assess the effect of pelvic lymph node dissection (PLND) extent on cancer-specific mortality (CSM) in prostate cancer (PCa) patients without lymph node invasion (LNI) treated with radical prostatectomy (RP). Methods: Within the Surveillance, Epidemiology, and End results (SEER) database (2004-2014), we identified patients with D'Amico intermediate- or high-risk characteristics who underwent RP with PLND, without evidence of LNI. First, multivariable logistic regression models tested for predictors of more extensive PLND, defined as removed lymph node count (NRN) ≥75th percentile. Second, Kaplan-Meier analyses and multivariable Cox regression models tested the effect of NRN ≥75th percentile on CSM. Finally, survival analyses were repeated using continuously coded NRN. Results: In 28147 RP and PLND patients without LNI, 67.3% versus 32.7% exhibited D'Amico intermediate- or high-risk characteristics. The median NRN was 6 (IQR 3-10), the 75th percentile defined patients with NRN ≥11. Patients with NRN ≥11 had higher rate of cT2/3 stage (29.8 vs 26.1%), GS ≥8 (25.7 vs 22.4%), and respectively more frequently exhibited D'Amico high-risk characteristics (34.6 vs 32.1%). In multivariable logistic regression models predicting the probability of more extensive PLND (NRN ≥11), higher biopsy GS, higher cT stage, higher PSA, more recent year of diagnosis, and younger age at diagnosis represented independent predictors. At 72 months after RP, CSM-free rates were 99.5 versus 98.1% for NRN ≥11 and NRN ≤10, respectively and resulted in a HR of 0.50 (P=0.01), after adjustment for all covariates. Similarly, continuously coded NRN achieved independent predictor status (HR: 0.955, P=0.01), where each additional removed lymph node reduced CSM risk by 4.5%. Conclusion: More extensive PLND at RP provides improved staging information and consequently is associated with lower CSM in D'Amico intermediate- and high-risk PCa patients without evidence of LNI. Hence, more extensive PLND should be recommended in such individuals.

High-risk prostate cancer (HRPCa) represents a heterogeneous disease with potential risk for local and distant progression. In these patients, a multi-modal approach consisting of neoadjuvant and/or adjuvant systemic therapies has been proposed. The aim of this review is to summarize the emerging roles of neoadjuvant and adjuvant therapies in HRPCa patients. Areas covered: This review collects the most relevant phase III randomized controlled trials (RCTs) testing the effect of neoadjuvant and adjuvant systemic therapies in combination with radical prostatectomy (RP) or radiotherapy (RT) for HRPCa patients. Specifically, the review examines the benefit provided by androgen deprivation therapy (ADT), chemotherapy (CHT), and novel antiandrogen agents in this setting. A search of bibliographic databases for peer-reviewed literature was conducted. Expert commentary: Three decades of RCTs demonstrated that adjuvant ADT is fundamental in HRPCa treated with RT. Conversely, ADT and CHT did not improve the survival of HRPCa patients managed with RP. The recent introduction of novel antiandrogen agents combined with an appropriated selection of patients at risk of cancer progression, may ultimately extend the indication of neoadjuvant and adjuvant therapy in surgical- and radio-treated patients.

The objective of this study was to investigate positive surgical margin (PSM) rates in patients with prostate cancer treated with radical prostatectomy (RP) and assess PSM impact on cancer-specific mortality (CSM).Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015), we identified men who underwent RP with pathologic T2 or T3a stage. Annual trends of PSM rates were plotted. Subgroups focused on geographic regions, namely the North Central, Northeast, South, and West. Cumulative incidence plots depicted other-cause mortality-adjusted CSM rates. Multivariable competing risks regression models tested the relationship between PSM and CSM. Subgroup analyses focused on pathologic stage, Gleason score, and geographic region.Of 153,329 patients treated with RP, 12.3% (n = 18,935) exhibited PSM. Overall, in pathologic T2 stage and pathologic T3a stage, PSM rates decreased during the study period from 18.7% to 9.7% (P .001), 15.7% to 7.3% (P .001), and 39.0% to 18.0% (P .001), respectively. In subgroup analyses focusing on geographic regions, PSM rates universally decreased. However, the magnitude differed. In multivariable competing risks regression models, PSM rates were associated with higher CSM (hazard ratio, 1.45; P .001). However, geographic regions failed to reach independent predictor status. Insufficient information about PSM focality, length, and associated Gleason score represent important limitations.It is encouraging that PSM rates decreased during the study period, even after stratification according to tumor stage. PSM decreased within the 4 examined geographic regions. However, the rate of decrease varied in magnitude, but geographic regions did not represent an independent predictor of PSM.

Background: Aborted radical prostatectomy (aRP) in lymph node (LN) metastatic (pN1) prostate cancer (PCa) patients showed worse survival in European patients. Contemporary rates of aRP are unknown in North America. Objective: To examine the rate of aRP and its effect on cancer-specific mortality (CSM) in contemporary North American patients. Design, setting, and participants: Within the Surveillance Epidemiology and End Results database (2004-2014), we identified 3719 pN1 PCa patients. Intervention: RP. Outcome measurements and statistical analysis: Incidence proportion and median survival of LN metastatic PCa patients who underwent aRP versus completed RP (cRP). Cumulative incidence plots and competing-risks regression (CRR) models tested CSM and other-cause mortality rates according to aRP versus cRP. The effect of selected variables on CSM rate was graphically depicted using LOESS methodology. All analyses were repeated after propensity score matching. Results and limitations: Between 2004 and 2014, the rate of aRP decreased from 20.4% to 5.6% (p< 0.001). Ten-year CSM rates were significantly higher after aRP (38.9% vs 21.6%) versus cRP (p< 0.001). In multivariable CRR models, aRP yielded higher CSM (hazard ratio [HR]: 1.99) than cRP. A higher 5-yr CSM rate was recorded after aRP through the entire range of baseline prostate-specific antigen (PSA) values and in patients with up to nine LN metastases. After propensity score matching, aRP resulted in overall higher CSM (HR: 1.72). Higher CSM was recorded after aRP for PSA values up to 50. ng/ml and in patients with up to seven LN metastases. Results were limited by a selection bias that applies to aRP patients. Conclusions: Of contemporary North American patients, 5% are affected by aRP. It confers a significant survival disadvantage that applies to patients with baseline PSA values up to 50. ng/ml and in those with up to seven LN metastases. Patient summary: Radical prostatectomy should not be aborted in pN1 prostate cancer individuals. Aborted radical prostatectomy (RP) still affects 5% of contemporary North American patients. It confers a significant survival disadvantage that was quantified in 13.5% higher cancer-specific mortality rate, which appears to apply even to patients with baseline prostate-specific antigen values up to 50. ng/ml and with up to seven lymph node metastases. An emphasis on the persistent rate of aborted RP is warranted, with the intent of further decreasing or ultimately eliminating such clinical practice.

The rate of noninterventional treatment (NIT) in prostate cancer (PCa) active surveillance (AS) candidates is on the rise. However, contemporary data are unavailable. We described community-based NIT rates within 16 Surveillance Epidemiology and End Results (SEER) registries between 2010 and 2014.We identified 23,360 PCa patients who fulfilled the University of California San Francisco AS criteria (prostate-specific antigen [PSA] 10 ng/mL, clinical T stage ≤ T2a, Gleason score ≤ 6, and positive cores 33%). Annual NIT rates as well as patient distribution according to PSA, age, number of positive cores, and clinical T stage were studied. Multivariable logistic regression analysis tested NIT predictors.Between 2010 and 2014, the NIT rate increased from 30.2% to 57.5% (P = .004). Within 16 SEER registries, NIT rates ranged from 25.9% to 62%. NIT rate increased uniformly within all examined registries. Of patient and tumor characteristics (PSA4 ng/mL, cT2a and1 positive core) only the proportion of NIT patients aged 65 years increased over time from 47.3% to 53.2% (P = .03). By multivariable logistic regression analysis predicting NIT rate, older age (odd ratio [OR] = 1.05), more contemporary year of diagnosis (OR = 1.41), and being unmarried (OR = 1.45) and uninsured (OR = 2.41) were independent predictors.The NIT rate has markedly increased across all examined SEER registries. Nonetheless, important differences distinguish those who received high-end NIT from low-end NIT. PCa characteristics of NIT patients remained unchanged over time. However, in addition to geographical differences in NIT rates, patient characteristics such as age, marital status, and insurance status represent potential NIT access barriers.

Background: Four nomograms are available for the prediction of lymph node invasion (LNI) prior to radical prostatectomy (RP): the Cagiannos, the 2012-Briganti, the Godoy, and the online-Memorial Sloan Kettering Cancer Center (MSKCC). None was tested in African Americans (AAs). Objective: To perform a validation and head-to-head comparison of four nomograms for the prediction of LNI in AAs. Design, setting, and participants: Within the Surveillance Epidemiology and End Results database (2010-2014), we identified 14 077 Caucasians and 2668 AAs with clinically localised prostate cancer. Intervention: RP and pelvic lymph node dissection (PLND). Outcome measurements and statistical analysis: Predicted and observed LNI rates for the four nomograms were tested between AAs and Caucasians with Heagerty's concordance index (C-index), calibration plots, decision curve analyses (DCAs), and nomogram-derived cut-offs for avoided PLND and missed LNI cases. Results and limitations: All C-index values were lower in AAs than in Caucasians: Cagiannos (76.1% vs 79.5%), Godoy (73.0% vs 79.4%), 2012-Briganti (73.3% vs 81.3%), and MSKCC (72.6% vs 81.6%). All four nomogram calibration plots showed invariably worse performances in AAs. In DCAs focusing on AAs, the Cagiannos nomogram provided the highest net benefit relative to the remaining three nomograms. In nomogram cut-off analyses testing the number of avoided PLND against the number of missed LNI cases, the Cagiannos nomogram yielded the best results when tested in AAs. However, in DCAs and cut-off analyses that compared AAs with Caucasians, AAs yielded less favourable outcomes regardless of which nomogram was tested. We lack a central pathology review and standardisation of PLND templates. Conclusions: In AAs, the Cagiannos nomogram provides the optimal results relative to the remaining three nomograms. Nonetheless, all tested nomograms yielded worse metrics in AAs than in Caucasians. Patient summary: All four tested nomograms can be equally considered in Caucasians. Conversely, the Cagiannos nomogram should be preferred in African Americans. 1. None of the available tools for the prediction of lymph node invasion in candidates to radical prostatectomy and pelvic lymph node dissection was tested in African American prostate cancer patients. 2. According to C-Index values, calibration proprieties, decision curve analyses, and nomogram-derived instances of avoided pelvic lymph node dissection that compared African Americans with Caucasians, African Americans yielded less favourable outcomes regardless of which nomogram was tested. 3. In the head-to-head comparison of the Cagiannos, Godoy, 2012-Briganti, and MSKCC nomograms in African Americans, the Cagiannos yielded the optimal results.

Background The benefit of cytoreductive nephrectomy (CNT) for cancer-specific mortality (CSM)-free survival is unclear in contemporary metastatic non-clear cell renal cell carcinoma (non-ccmRCC) patients. Objective To assess the role of CNT in non-ccmRCC patients. Design, setting, and participants Within Surveillance, Epidemiology, and End Results registry (2001–2014), we identified patients with non-ccmRCC. Intervention CNT versus no CNT in non-ccmRCC patients. Outcome measurements and statistical analysis Multivariable logistic regression, cumulative incidence, competing-risks regression models, incremental survival benefit (ISB), conditional survival, and landmark analyses were performed. Sensitivity analyses focused on histological subtypes and most contemporary patients (2010–2014). Results and limitations Of 851 patients with non-ccmRCC, 67.6% underwent CNT. In multivariable logistic regression, year of diagnosis in contemporary ( p 0.001) and intermediate ( p =0.008) tertiles, as well as age ≥75 yr ( p 0.001) yielded lower CNT rates. Cumulative incidence showed 2-yr CSM of 52.6% versus 77.7%, respectively, after CNT versus no CNT. CSM after CNT versus no CNT was invariably lower in all histologic subtypes and in contemporary patients. Multivariable competing-risks regression models predicting CSM favored CNT (hazard ratio [HR]: 0.38, confidence interval: 0.30–0.47, p 0.001) in all patients and in all subgroups defined by histologic subtypes (HR: 0.14–0.43, all p ≤0.02), as well as in contemporary patients (HR: 0.32, p 0.001). The ISB analyses yielded statistically significant and clinically meaningful CSM-free survival benefit of +3 mo after CNT versus no CNT in individuals with observed CSM-free survival ≤24 mo. The 2-yr CSM-free survival increased from baseline of 46.1% versus 19.4% (Δ=26.7%, p 0.001) to 70.3% versus 54.4% (Δ=15.9%, p =0.005) after CNT versus no CNT, in patients that survived 12 mo, respectively. Landmark analyses rejected bias favoring CNT. Data were retrospective. Conclusions CSM is lower after CNT for non-ccmRCC in all histologic subtypes and in contemporary patients except for unproven ISB in collecting duct patients. This observation should encourage greater CNT consideration in non-ccmRCC. Patient summary Cytoreductive nephrectomy appears to improve survival in metastatic non-clear cell renal cell carcinoma, but it is used infrequently.

Introduction: Local therapy (LT) may offer a survival advantage in highly select, newly diagnosed metastatic prostate cancer (mPCa) patients. However, it is unknown whether the benefits vary in Caucasian vs. African American (AA) patients. Methods: Within the Surveillance Epidemiology and End Results (SEER) database (2004–2014), we focused on Caucasians and AA patients with newly diagnosed mPCa treated with LT: radical prostatectomy (RP) and brachytherapy (RT). Endpoints consisted of cancer-specific mortality (CSM) and overall mortality (OM). Kaplan-Meier analyses and multivariable Cox regression models tested for racial difference in CSM and OM. Results: Between 2004 and 2014, we identified 408 (77.2%) Caucasians and 121 (22.8%) AAs with newly diagnosed mPCa treated with LT: RP (n=357) or RT (n=172). According to race, when LT is defined as RP, Caucasian patients had a significantly longer survival vs. AA patients: CSM-free survival 123 vs. 63 months (p=0.004) and OM-free survival 108 vs. 46 months (p=0.002). The CSM and OM benefits were confirmed in multivariable analyses (hazard ratio [HR] 0.56, p=0.01 for CSM; HR 0.60, p=0.01 for OM). However, no differences in CSM or OM were recorded according to race when LT consisted of RT. Conclusions: Our results indicate that race is not associated with difference in survival after LT in mPCa patients. However, when focusing on RP-treated patients, Caucasian race is associated with higher CSM and OM rates relative to AA race. This racial difference does not apply to RT. Our findings should be considered in future prospective trials for the purpose of preplanned stratification according to race.

Radical prostatectomy (RP) represents one standard of care for patients with localized prostate cancer and is associated with several established postoperative complications.We tested the relationship between RP early postoperative outcomes and age within a population-based data repository.Within the National Inpatient Sample database (2008-2013), we identified patients who underwent robotically assisted or open RP.Multivariable logistic regression (MLR), multivariable Poisson regression (MPR), and linear regression models were used. Cubic spline graphically depicted the relationship between age and complications.Overall, 68780 patients underwent RP with a median age of 62 yr (interquartile range: 57-67 yr). In MLR models, patient age represented an independent predictor of overall [odds ratio (OR): 1.02, p0.001], intraoperative (OR: 1.03, p0.001), cardiac (OR: 1.03, p0.001), miscellaneous medical (OR: 1.02, p0.001), miscellaneous surgical (OR: 1.01, p=0.01), pulmonary (OR: 1.02, p0.001), and vascular complications (OR: 1.05, p0.001); blood transfusions (OR: 1.02, p0.001); and bowel obstruction (OR: 1.02, p0.001). In MPR models, patient age was associated with longer stay (OR: 1.001, p=0.02). Similar results were recorded after adjustment for clustering in stratified analyses (70 vs ≥70 yr) and in the subgroup of patients that underwent robotically assisted RP. For nine out of twelve examined outcomes, a virtually direct relationship existed with increasing age, in cubic spline analyses.Virtually all early postoperative RP complications are directly related to age. In consequence, these observations should be considered from an individual patient perspective as well as from a health management perspective.RP is provided through a wide patient age spectrum. Virtually all early postoperative RP complications are directly related to age. Individual patient's age needs to be considered in treatment decision-making.

Partial nephrectomy (PN) is technically feasible in patients with metastatic renal cell carcinoma (mRCC). We tested the contemporary effect of PN on cancer-specific mortality (CSM), other-cause mortality (OCM) and early postoperative outcomes compared to radical nephrectomy (RN) in mRCC patients.In the first part, we identified surgically treated mRCC patients within the SEER database (2004-2013). After propensity-score (PS) matching, cumulative incidence plots and multivariable competing-risks regression (CRR) models were used. In the second part, we identified surgically treated mRCC patients within the NIS database (2004-2013). After PS matching, multivariable logistic regression (MLR) and multivariable Poisson regression (MPR) models were used.Within the SEER database, 217 (4.2%) of 5171 mRCC patients underwent PN. After 4:1 PS matching, multivariable CRR models showed lower OCM rates in PN patients (hazard ratio [HR]: 0.23, p = 0.01). No difference in CSM was reported in PN vs. RN patients (p = 0.08). Within the NIS database, 226 (4.4%) of 5138 patients underwent PN. After 4:1 PS matching, MLR showed lower rates of transfusions (odds ratio [OR]: 0.46, P 0.001), intraoperative (OR: 0.33, p = 0.02) and miscellaneous surgical complications (OR: 0.42, p = 0.009) in PN vs. RN patients. No difference in overall complications (OR: 1.00, p = 0.9) and in-hospital mortality (OR: 1.2, p = 0.8) was observed. In MPR, PN did not affect LOS (OR: 0.94, p = 0.3).We demonstrate that PN is associated with lower OCM in the setting of mRCC, but not with differences in other examined endpoints. In consequence, PN merits greater consideration in the context of mRCC.

Radical cystectomy represents the standard of care for muscle-invasive bladder cancer (MIBC). Due to its novelty the use of robotic radical cystectomy (RARC) is still under debate. We examined intraoperative and postoperative morbidity and mortality in addition to impact on length of stay (LOS) and total hospital charges (THCGs) of RARC compared with open radical cystectomy (ORC).Within National Inpatient Sample (2008-2013), we identified patients with nonmetastatic bladder cancer treated with either ORC or RARC. We relied on inverse probability of treatment weighting to reduce the effect of inherent differences between ORC vs RARC. Multivariable logistic regression (MLR) and multivariable Poisson regression (MPR) models were used.Of all 10,027 patients, 12.6% underwent RARC. Between 2008 and 2013, RARC rates increased from 0.8% to 20.4% [estimated annual percentage change (EAPC): +26.5%, 95% confidence interval (CI): +11.1 to +48.3; p = 0.035] and RARC THCGs decreased from 45,981 to 31,749 United States dollars (EAPC: -6.8%, 95% CI: -9.6 to -3.9; p = 0.01). In MLR models RARC resulted in lower rates of overall complications [odds ratio (OR): 0.6; p 0.001] and transfusions (OR: 0.44; p 0.001). In MPR models, RARC was associated with shorter LOS (relative risk 0.91; p 0.001). Finally, higher THCGs (OR: 1.09; p 0.001) were recorded for RARC. Data are retrospective and no tumor characteristics were available.RARC is related to lower rates of overall complications and transfusions rates. In consequence, RARC is a safe and feasible technique in select MIBC patients. Moreover, RARC is associated with shorter LOS, although higher THCGs.

Background: Robotically assisted radical prostatectomy (RARP) has become the most frequently used surgical approach for patients treated with radical prostatectomy (RP) for localized prostate cancer (PCa). Previous studies reported higher total hospital charges (THCs) for RARP than open RP (ORP). We hypothesized that based on increasing RARP surgical expertise, differences in THCs between RARP and ORP should have decreased or even disappeared in the United States in most contemporary years. Patients and methods: Within the National Inpatient Sample database (2008–2015), we identified patients who underwent RARP or ORP. Multivariable linear regression models with adjustment for clustering were used to test for differences in THCs. Subgroup analyses focused on geographical regions, defined as West, Midwest, South and Northeast. Results: Of 83,693 RP patients, 51,363 (61.4%) underwent RARP. RARP rates increased from 13.1 to 81.5% (p = 0.04). Overall, median THCs were $11,898 vs. $10,162 (p < 0.001) for RARP vs. ORP, respectively. After adjustment for complications, length of stay and clustering, RARP was associated with higher THCs ($3124 more for each RARP, p < 0.001). Additional charges for RARP did not change over time (p = 0.3). However, additional charges for RARP were highest in the West ($4610, p < 0.001), followed by the Midwest ($3278, p < 0.001), the South ($2906, p < 0.001) and the Northeast ($2216, p < 0.001). Conclusion: RARP rates have increased exponentially from 13.1 to over 80%. Similar rates were identified across all four geographical regions. RARP THCs exceeded those of ORP. Finally, important regional differences in RARP THCs were identified and persisted even after most detailed adjustment for population differences.

To test the effect of African-American race on cancer specific mortality (CSM) in clear cell metastatic renal cell carcinoma (ccmRCC) and non-ccmRCC.Within Surveillance, Epidemiology and End Results registry (2001-2014), we identified patients with ccmRCC and non-ccmRCC. We relied on propensity score (PS) matching to reduce the effect of inherent differences between African-American vs. Caucasian patients. After PS matching that included access to cytoreductive nephrectomy (CNT), cumulative incidence, competing-risks regression (CRR) models and landmark analyses tested the effect of race on CSM.Before PS matching, African-American patients accounted for 7.0 and 24.5% of respectively ccmRCC (N = 6742) and non-ccmRCC patients (N = 766). After PS matching, African-American patients accounted for 22.3 and 33.5% of respectively ccmRCC (N = 2050) and non-ccmRCC (N = 391) matched cohorts. In multivariable CRR models focusing on ccmRCC, higher CSM was recorded in African-Americans (HR:1.27, p 0.001). Conversely, in non-ccmRCC, lower CSM was recorded in African-Americans (HR:0.54, p 0.001). Landmark analyses rejected the hypothesis of immortal time bias.African-Americans experienced higher CSM in ccmRCC. Conversely, African-Americans experienced lower CSM, when diagnosed with non-ccmRCC. These differences are independent of access to CNT and warrant further study since they may have an impact on efficacy or access to systemic therapies.

Background: We hypothesized that a cut-off in positive lymph node (LN) counts may discriminate between cancer-specific mortality (CSM) rates in clinically localized prostate cancer patients treated with radical prostatectomy (RP). Objective: To test this relationship, we relied on different LN count cut-offs, as well as the continuously coded number of positive LNs (NPN). Methods: Within the Surveillance, Epidemiology, and End Results database (2004-2014), we identified patients with D'Amico intermediate- or high-risk characteristics who underwent RP and pelvic LN dissection, regardless of pathologic LN stage. Kaplan-Meier analyses and multivariable Cox regression models tested the effect of LN invasion (LNI) on CSM, according to the NPN. Results: Of 30. 016 patients treated with RP, 6.2% (n = 1869) exhibited LNI, with respectively higher rates of LNI in patients with D'Amico high- versus intermediate-risk characteristics (11.6% vs 3.4%). Overall, the median age was 63. yr, median prostate-specific antigen value was 6.6. ng/ml and the median number of removed LNs was six. At 60 mo after RP, CSM rates were, respectively, 6.0% versus 0.8% for patients with and without LNI: multivariable hazard ratio (HR) 4.4 (p

Purpose To quantify the prognostic effect of the location of prostate cancer (PCa) metastases on cancer-specific mortality (CSM) and the rate of other-cause mortality (OCM) in contemporary newly diagnosed metastatic PCa (mPCa) patients. Patients and Methods Within the Surveillance Epidemiology and End Results database (2004-2014), we focused on newly diagnosed mPCa patients. Data were stratified according to the site of metastases and age group. Cumulative incidence smoothed plots were generated for CSM and OCM at 5 years after diagnosis, according to the competing-risks methods. Multivariable competing-risks analyses tested the effect of the location of PCa metastases on CSM. Results Among 18,404 patients with mPCa, the majority had exclusively bone metastases (63.6%). At 5 years, CSM rate was 59.7% and OCM rate was 14%. According to the location of metastases, CSM rates were 44.5%, 57.9%, 67.1%, 62.7%, 66%, and 76.3% for exclusively lymph node (LN), exclusively bone, bone plus LN, exclusively visceral, visceral plus LN, and visceral plus LN and bone disease, respectively. In multivariable competing-risks models, PCa-specific mortality rate was 1.58-, 1.79-, 1.91-, 2.10-, and 2.47-fold higher in patients with exclusively bone, bone plus LN, exclusively visceral, visceral plus LN, and visceral plus bone and LN involvement compared to those with exclusively LN metastases (all P Conclusion Patients with concomitant visceral, bone, and LN metastases have the worst prognosis. Similarly, when either bone or visceral metastases coexist with concomitant LN metastases, CSM rates are higher than when no concomitant LN metastases are present.

No prospective data examined the effect of radical prostatectomy (RP) vs. external beam radiotherapy (EBRT) in locally advanced prostate cancer (PCa). We aimed to compare survival outcomes of RP and EBRT in patients harboring cT3N0-1 PCa. Within the SEER database (2004–2014), we identified 5500 cT3N0-1 PCa patients. Cumulative incidence plots and competing-risks regression models (CRRs) tested cancer-specific mortality (CSM) and other cause of mortality (OCM) according to treatment type. The multivariable relationship between baseline prostate-specific antigen (PSA) values and 10-year CSM after either RP or EBRT was graphically depicted using the LOESS smoothing method. Sensitivity analyses were performed in cT3N0-only patients, after OCM propensity score matching, and through landmark analyses. Ten-year CSM and OCM rates were significantly higher after EBRT (15.8 and 28.2%) than RP (8.1 and 10.4%) (all p

Contemporary data regarding the benefit of radiotherapy in surgically treated retroperitoneal sarcoma are scarce. The aim of the study was to evaluate the effect of radiotherapy on cancer specific mortality in surgically treated patients according to tumor size, histological subtype and grade.Within Surveillance, Epidemiology, and End Results database (2004-2014), we identified 1226 patients with non-metastatic retroperitoneal sarcoma. Univariable and multivariable logistic regression models tested for predictors of radiotherapy delivery. Univariable and multivariable Cox regression models tested the effect of radiotherapy on cancer specific mortality in the overall population. Subgroup analyses explored the result of tumor grade and tumor size on radiotherapy effect. All analyses were repeated after adjustment according to inverse probability of treatment. Additionally, all analyses were subjected to 1000 bootstrap resamples for internal validation.Radiotherapy was delivered in 372 patients (30.3%). In univariable and multivariable logistic regression models high grade (OR: 1.46, CI:1.12-1.90; p = 0.006), and leiomyosarcoma histologic subtype (OR: 2.14, CI: 1.55-2.95; p 0.001) predicted radiotherapy delivery. In the overall population multivariable Cox regression models showed lower cancer specific mortality (HR: 0.73, CI: 0.55-0.96; p = 0.025) with radiotherapy. In subgroup analyses multivariable Cox regression models showed radiotherapy benefit predominantly in high grade, large tumor size retroperitoneal sarcomas (HR 0.51: C.I.: 0.30-0.86; p = 0.02).In this retrospective report, delivery of radiotherapy was associated with lower cancer specific mortality in high grade, large tumor size retroperitoneal sarcoma patients. Our findings are predominantly representative of liposarcomas and leiomyosarcomas that accounted for 90% of study population. Further study is needed to evaluate the role of radiotherapy in retroperitoneal sarcoma patients.

Objectives: To test rates over time of robotic partial and radical nephrectomy (RPN and RRN) at teaching vs nonteaching institutions and to examine associated complication rates and length of stay. Materials and Methods: Within the National Inpatient Sample (2008-2013), after stratification according to institutional teaching status, we examined the rates of robotic, open, and laparoscopic PN and RN. Subsequently, we tested complication rates and length of stay associated with RPN or RRN according to institutional teaching status. We relied on estimated annual percentage change (EAPC) with the least squares linear regression to test temporal trends and on multivariable logistic regression (MLR) and Poisson regression models to test complication rates and length of stay. Results: Overall, 4070 and 1683 RPN and RRN were identified. In MLR, RPN rates were lower at teaching vs nonteaching institutions (odds ratio [OR]: 0.79, p < 0.001). RPN increased at similar rates over time at teaching and nonteaching institutions (EAPC: +32.1% and +30.1%, all p < 0.05). In MLR, RRN rates were similar at teaching and nonteaching institutions (p: 0.4). RRN rate increase over time was of similar magnitude at teaching vs nonteaching institutions (EAPC: +35.5% and +43.0%, all p < 0.05). RPN at teaching institutions yielded higher genitourinary complication rates (OR: 1.46, p: 0.01). RRN at teaching institutions resulted in lower respiratory complications (OR: 0.66, p: 0.04) and shorter length of stay (rate ratio [RR]: 0.93, p: 0.01), but higher intraoperative complication rates (OR: 3.39, p: 0.04). Conclusion: Despite statistically significant differences in rates of RPN use, according to the institutional teaching status and despite statistically significant difference in selected complications, no meaningful differences distinguish teaching vs nonteaching institution when RPN and RRN are considered.

Objectives: To test for racial disparities in lymph node dissection rates, lymph node dissection extent, lymph node invasion rates and cancer-specific mortality in North American African Americans versus non-Hispanic whites, at radical prostatectomy for clinically localized prostate cancer. Methods: Within the Surveillance, Epidemiology and End Results database (2010–2014), we identified 58 974 African Americans or non-Hispanic whites with prostate cancer, who underwent radical prostatectomy with available clinical stage, prostate-specific antigen and biopsy Gleason score. Annual trends were examined. Logistic regression models focused on lymph node dissection rates, lymph node dissection extent (number of removed lymph nodes) and lymph node invasion. Cox regression models tested for differences in cancer-specific mortality. Multivariable models were adjusted for D'Amico risk groups, age and year. Models predicting lymph node invasion and cancer-specific mortality were additionally adjusted for lymph node dissection extent. Results: Among all patients, 14.5% were African Americans. Lymph node dissection was carried out in 60.0% of African Americans versus 59.5% of non-Hispanic whites (P = 0.4). The median number of removed lymph nodes was five in African Americans versus six in non-Hispanic whites (P < 0.001). Furthermore, 3.1% versus 3.3% of African Americans and non-Hispanic whites, respectively, harbored lymph node invasion (P = 0.3). In multivariable logistic regression models African American race did not affect lymph node dissection or lymph node invasion rates, but lymph node dissection extent was lower in African Americans (hazard ratio 0.9; P < 0.001). No statistical differences in cancer-specific mortality were identified according to race. Conclusions: Contemporary North American African American patients treated with radical prostatectomy have equal access to lymph node dissection, the same lymph node invasion rates and the same cancer-specific mortality rates as non-Hispanic whites. However, the extent of lymph node dissection is lower in African Americans. The results regarding lymph node dissection rates are encouraging. However, improvements are required regarding lymph node dissection extent in African Americans.

Background: Historically, partial nephrectomy (PN) showed no benefit on other-cause mortality (OCM) in elderly patients with small renal masses. Objective: To test the effect of PN versus radical nephrectomy (RN) on OCM, cancer-specific mortality (CSM), as well as 30-d mortality in patients with nonmetastatic T1a renal cell carcinoma (RCC), aged ≥75 yr old. Design, setting, and participants: Within the Surveillance, Epidemiology and End Results registry (2004-2014), we identified surgically treated patients with nonmetastatic pT1a RCC aged ≥75 yr. Outcome measurements and statistical analysis: We relied on propensity score (PS) matching to reduce the effect of inherent differences between PN and RN. After PS matching, cumulative incidence, multivariable competing-risks regression (CRR) and logistic regression models were used. LOESS plots graphically depicted the relation between nephrectomy type and OCM after adjustment for all the covariates. Landmark analyses at 6 mo tested for immortal time bias. Results and limitations: Of all 4541 patients, 41.6% underwent PN. After 1:1 PS matching, 2826 patients remained. In multivariable CRR models, lower OCM rates were recorded in PN patients (hazard ratio [HR]: 0.67, confidence interval [CI]: 0.54-0.84; p< 0.001). LOESS plots showed lower OCM rates after PN across all examined ages. Lower CSM rates were also recorded in PN patients (HR: 0.64, CI = 0.44-0.92; p = 0.02). Landmark analyses rejected the hypothesis of immortal time bias. Finally, PN did not result in different 30-d mortality rates (odds ratio: 1.87; CI: 0.79-4.47; p = 0.2) versus RN. Data are retrospective. Conclusions: PN results in lower OCM in elderly patients with pT1a RCC. Moreover, PN does not contribute to higher CSM or 30-d mortality in patients aged ≥75 yr. In consequence, PN should be given strong consideration, even in elderly patients. Patient summary: Partial nephrectomy (PN) may protect from renal insufficiency, hypertension, and other unfavorable health outcomes, even in elderly patients. This protective effect results in lower other-cause mortality. Moreover, PN benefits are not undermined by higher cancer-specific mortality or 30-d mortality. Partial nephrectomy should be given strong consideration even in elderly patients.

Background: Radical cystectomy (RC) may occasionally be performed in individuals with metastatic urothelial carcinoma of the bladder (mUCB). However, the role of lymph node dissection (LND) for such cases is unknown. Thus, we tested the effect of RC on cancer-specific mortality (CSM) and overall mortality in mUCB patients and the effect of LND and its extent on CSM. Patients and Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2013), we identified patients with mUCB who underwent RC with or without LND or non-RC management. Kaplan-Meier analyses and multivariable Cox regression models (CRMs) were used, after propensity score matching. The number of removed nodes best predicting CSM was identified using cubic splines and then was tested in multivariable CRMs. Results: Of 2314 patients, 319 (13.8%) underwent RC. After 2:1 propensity score matching, CSM-free survival was 14 versus 8 months (P

Objectives To investigate lymph node invasion (LNI) rates in prostate cancer (PCa) patients. Recent studies demonstrated an inverse stage migration in PCa patients toward more advanced and unfavorable diseases. We hypothesized that this trend is also evident in LNI rates, in PCa patients treated with radical prostatectomy (RP) and pelvic lymph node dissection (PLND). Patients and methods Within the Surveillance, Epidemiology, and End Results database (2004–2014), we identified patients who underwent RP and PLND. Annual trends of LNI rates and PLND extent were plotted. Univariable and multivariable logistic regression models tested the hypothesis that LNI rates are increasing annually, even after adjustment for clinical or pathological characteristics. Results Of 96,874 patients treated with RP and PLND, 4.1% (n = 4,002) exhibited LNI. The rate of LNI (2.5%–6.6%.), the mean (6.5–8.4) and median (5–6) number of removed lymph nodes increased during the study period. In multivariable logistic regression models, more contemporary year of diagnosis was associated with higher LNI rate, when year of diagnosis was modeled as a continuous, categorized or cubic spline variable, with adjustment for either clinical (prostate specific antigen, clinical tumor stage, and biopsy Gleason group) or pathological characteristics (pathologic tumor stage and Gleason group), as well as PLND extent (number of removed lymph nodes). Conclusion We confirmed the hypothesis about increasing LNI rate over time in RP patients. This observation implies an increasing rate of unfavorable PCa defined as LNI. This finding is novel for contemporary epidemiological North American or European databases.

Recent studies demonstrated ongoing inverse stage migration in prostate cancer (PCa) patients towards more advanced and unfavorable tumors. The USPSTF grade D recommendation may impact this trend in North American patients. We assessed contemporary stage migration and treatment trends in a large North American cohort diagnosed with PCa 2009–2014. Time-trend analyses were performed in patients within the Surveillance, Epidemiology, and End Results database, with complete data of clinical tumor stage, biopsy Gleason score, and validated PSA values, resulting in 211,645 assessable patients. Patients were stratified according to their different treatment methods [radical prostatectomy (RP), radiotherapy (RT), and no local treatment (NLT)] and according to clinical and pathological risk stratification (D’Amico and CAPRA-S score). Over time, proportions of D’Amico low-risk (LR) decreased, with an increase in intermediate-to-high-risk (IR/HR) patients. These trends were more distinct in men ≥ 70 years. NLT proportions increased, most notably in D’Amico LR and/or older patients. Conversely, RP proportions remained stable in younger HR and increased in older HR patients. Similar patterns were demonstrated in the RP-treated subgroup: D’Amico HR, pT3, and/or lymph-node invasion or CAPRA-S HR proportions increased from 23.5 to 30.8, 24.3 to 32.9, and 10.7 to 16.3% (each p ≤ 0.015). Inverse stage migration with increase of unfavorable PCa continues in most contemporary North American patients. However, a paradigm shift to treat LR patients with less invasive methods (NLT) was demonstrated. Contrary, HR patients increasingly undergo LT. Future studies with long-term follow-up might answer if inverse stage migration vs. treatment trends translate into different PCa metastases/mortality rates vs. proposed NLT benefits, particularly related to USPSTF-recommended reduced PSA screening.