Preoperative proteinuria correlates with renal function after partial nephrectomy for renal cell carcinoma.

PURPOSE: Preoperative proteinuria is a prognostic factor of chronic kidney disease (CKD). We assessed the association between preoperative proteinuria and postoperative renal function after partial nephrectomy (PN). METHODS: We retrospectively reviewed our records of patients with a single malignant renal mass who underwent PN between 2000 and 2021. Patients with data on preoperative proteinuria were included. Baseline characteristics and eGFR differences over time between patients with and without proteinuria were evaluated. Univariate and multivariable logistic regression models (LRM) tested for presence of CKDIII or higher at 12-month and at last follow-up. RESULTS: Two hundred ninety-five patients were included. Twenty-two of them had preoperative proteinuria. No differences of age, smoking status, hypertension or diabetes, tumor size and use of ischemia were observed. Patients with proteinuria had a higher rate of CKD-III at baseline. At a median follow-up of 46.5 months (IQR 19-82), 117 patients developed de novo CKD-III, without differences in the two groups. No differences in decline in eGFR were observed. At univariate LRM, predictors of CKD-III at 12 months after PN were preoperative proteinuria (OR 3.2, 95%CI 1.4-7.8, p = 0.005), age and baseline eGFR, while predictors of CKD-III at last follow-up were age and baseline eGFR. At multivariable LRM, only baseline eGFR predicted CKD-III at 12-month and at last-follow-up. CONCLUSIONS: Preoperative eGFR is the only independent predictor of long-term renal function after PN. Preoperative proteinuria correlates with renal function at 12 months. Proteinuria should be assessed before PN to identify patients at higher risk of renal functional deterioration in the 12 months following PN.

Prognostic role of the systemic immune-inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

PURPOSE: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS). RESULTS: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis. CONCLUSIONS: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.

Radical cystectomy plus chemotherapy in patients with pure squamous cell bladder carcinoma: a population-based study.

PURPOSE: To test the effect of perioperative chemotherapy (CHT) on overall mortality (OM) and cancer-specific mortality (CSM) in patients with locally advanced or metastatic squamous cell carcinoma of the urinary bladder (SCC UB). METHODS: Within the Surveillance, Epidemiology and End Results database (1988-2016), we identified 1,018 SCC UB patients (664 T3-4aN0M0, 197 TanyN1-3M0 and 156 T4bN0-3 or M1), who underwent radical cystectomy with or without perioperative chemotherapy administration. Inverse probability of treatment-weighting (IPTW), Kaplan-Meier plots and Cox-regression models (CRMs) were used. RESULTS: CHT was administrated in 116 (17.5%) T3-4aN0M0, 77 (39.1%) TanyN1-3M0 and 47 (30.1%) T4bN0-3 or M1 patients. IPTW-adjusted 2-year cancer-specific survival (CSS) was 66.5 vs. 71.5% (p = 0.19), 60.9 vs. 29.5% (p < 0.001) and IPTW-adjusted 1-year CSS was 46.2 vs. 31.1% (p = 0.03) for CHT vs. no CHT administration in T3-4aN0M0, TanyN1-3M0 and T4bN0-3 or M1, respectively. In multivariable IPTW-adjusted CRMs, chemotherapy was an independent predictor of lower CSM in TanyN1-3M0 (HR 0.44) and in T4bN0-3 or M1 (HR 0.60), but not in T3-4aN0M0 (p = 0.6) patients. Virtually the same results were obtained on OM, as well as without IPTW-adjustment and after stratification according to age and gender. CONCLUSIONS: The use of perioperative CHT in patients with SCC UB confers survival benefit in the presence of T4b disease, lymph node or distant metastases. Conversely, patients with locally advanced disease but negative lymph node invasion do not benefit from its use. Pending higher quality data from prospective trials, these data should encourage the use of perioperative CHT in those high-risk patient groups.

Comparison of survival outcomes in patients with metastatic papillary vs. clear-cell renal cell carcinoma: a propensity-score analysis.

BACKGROUND: To compare survival outcomes of metastatic patients harbouring either papillary (pRCC) or clear-cell (ccRCC) renal cell carcinoma in overall population and according to treatment modality. METHODS: Within the Surveillance, Epidemiology and End Results database (2006-2015), we identified 6800 patients (585 papillary and 6215 clear-cell) with metastatic RCC. Propensity-score (PS) matching, Kaplan-Meier plots and multivariable Cox-regression models (CRMs) were used. RESULTS: Overall, 585 (8.6%) patients harboured pRCC. Rates of nodal metastases were higher in patients with pRCC (49.7 vs. 23.3%; p < 0.001). Median overall survival (OS) was 13 vs. 18 months for pRCC vs. ccRCC patients. After multivariable adjustments, no difference in OS was recorded. Furthermore, after propensity-score matching, virtually the same results were recorded. Median OS of pRCC vs. ccRCC was 8 vs. 4 months for no treatment (NT), 11 vs. 12 months for targeted therapy alone (TT), 17 vs. 35 months for cytoreductive nephrectomy alone (CN) and 18 vs. 25 months for combination of CN with TT. CONCLUSIONS: Metastatic pRCC patients exhibit poor survival, regardless of treatment received. Moreover, pRCC patients are more likely to present nodal metastases, compared to ccRCC patients, as demonstrated by twofold higher rates of lymph node invasion at diagnosis. These observations indicate that papillary variant represents more prognostically unfavorable tumor histology, in the context of metastatic RCC.

Sex- and age-related differences in the distribution of bladder cancer metastases.

OBJECTIVE: Our objective was to investigate age- and sex-related differences in the distribution of metastases in patients with metastatic bladder cancer. METHODS: Within the National Inpatient Sample database (2008-2015), we identified 7040 patients with metastatic bladder cancer. Trend test and Chi-square test analyses were used to evaluate the relationship between age and site of metastases, according to sex. RESULTS: Of 7040 patients with metastatic bladder cancer, 5226 (74.2%) were men and 1814 (25.8%) were women. Thoracic, abdominal, bone and brain metastases were present in 19.5 vs. 23.0%, 43.6 vs. 46.9%, 23.9 vs. 18.7% and 2.4 vs. 2.9% of men vs. women, respectively. Bone was the most common metastatic site in men (23.9%) vs. lung in women (22.4%). Increasing age was associated with decreasing rates of abdominal (from 44.9 to 40.2%) and brain (from 3.2 to 1.4%) metastases in men vs. decreasing rates of bone (from 21.0 to 13.3%) and brain (from 5.1 to 2.0%) metastases in women (all P < 0.05). Finally, rates of metastases in multiple organs also decreased with age, in both men and women. CONCLUSIONS: The distribution of metastases in bladder cancer varies according to sex. Moreover, differences exist according to patient age and these differences are also sex-specific. In consequence, patient age and sex should be considered in the interpretation of imaging, especially when findings are indeterminate.

The effect of age on cancer-specific mortality in patients with prostate cancer: a population-based study across all stages.

PURPOSE: To test the effect of age on cancer-specific mortality (CSM) in most contemporary prostate cancer (PCa) patients of all stages and across all treatment modalities. METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 579,369 PCa patients. Cumulative incidence plots and multivariable competing-risks regression analyses (MCR) were used. Subgroup analyses were performed according to ethnicity (African-Americans), clinical stage (T1-2N0M0, T3-4N0M0, TanyN1M0, and TanyNanyM1), as well as treatment modalities. RESULTS: Patient distribution was as follows: 142,338 (24.6%) < 60 years; 113,064 (19.5%) 60-64 years; 127,158 (21.9%) 65-69 years; 94,782 (16.4%) 70-74 years; and 102,027 (17.6%) ≥ 75 years. Older patients harbored worse tumor characteristics and more frequently received no local treatment. Overall, 10-year CSM rates were 4.8, 5.3, 5.9, 7.6, and 14.6%, respectively, in patients aged < 60, 60-64, 65-69, 70-74 ,and ≥ 75 years (p < 0.001). In MCR focusing on the overall cohort and T1-2N0M0 patients, older age independently predicted higher CSM, but not in T3-4N0-1M0-1 patients. CONCLUSIONS: Older age was associated with higher grade and stage and independently predicted higher CSM in T1-2N0M0 patients, but not in higher stages. Differences in diagnostics and therapeutics seem to affect elderly patients within T1-2N0M0 PCa and should be avoided if possible.

Racial and ethnic differences in survival in contemporary metastatic renal cell carcinoma patients, according to alternative treatment modalities.

PURPOSE: To test the association between African-American race and overall mortality (OM) rates in patients with metastatic renal cell carcinoma (mRCC). METHODS: Within the Surveillance, Epidemiology, and End Results registry (2006-2015), we identified patients with clear cell (ccmRCC) and non-clear cell mRCC (non-ccmRCC). African-Americans, Caucasians, and Hispanics were identified. Stratification was made according to histology and treatments: (1) no treatment, (2) systemic therapy (ST), (3) cytoreductive nephrectomy (CNT), (4) CNT + ST. Kaplan-Meier plots and multivariable Cox regression analyses were used. RESULTS: Of ccmRCC patients, 410 (7%), 4353 (75%), and 1005 (17%) were African-American, Caucasian, and Hispanic, respectively. Of non-ccmRCC patients, 183 (25%), 479 (65%), and 77 (10%) were African-American, Caucasian, and Hispanic, respectively. In ccmRCC, African-Americans were associated with higher OM rates (HR 1.20; 95% CI 1.05-1.37). Conversely, in non-ccmRCC, African-Americans were associated with lower OM rates (HR 0.75; 95% CI 0.59-0.97). CONCLUSION: African-American race is associated with prolonged survival in non-ccmRCC, but it is also associated with lower survival rates in ccmRCC. The exception to these observations consisted of patients treated with combination of CNT + ST for either ccmRCC or non-ccmRCC.

Renal Cell Carcinoma: Comparison between Variant Histology and Clear Cell Carcinoma across All Stages and Treatment Modalities.

PURPOSE: We evaluated stage at presentation and cancer specific mortality according to variant histology relative to clear cell renal cell carcinoma. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results registry (2001-2016) we identified variant histology and clear cell renal cell carcinoma cases. Cumulative incidence plots, multivariate Cox regression models matched for stage, grade and other patient characteristics addressed cancer specific mortality. Subgroup analyses relied on inverse probability treatment weighting according to nephrectomy type. RESULTS: Of all 69,785 patients with renal cell carcinoma 2,495 harbored variant histology (3.6%). Of patients with variant histology 70.1% (1,748) harbored sarcomatoid vs 11.2% (280) collecting duct vs 7.6% (190) mesenchymal vs 3.8% (94) neuroendocrine vs 2.9% (72) renal medullary vs 2.5% (62) mucinous tubular and spindle cell, and 2.0% (49) rhabdoid tumors. All patients with variant histology exhibited more advanced TNM stage at diagnosis than clear cell renal cell carcinoma, except for mucinous tubular and spindle cell. After matching with G4 clear cell renal cell carcinoma, collecting duct (multivariate HR 1.6, p <0.01), sarcomatoid (HR 1.8, p <0.01), renal medullary (HR 1.7, p=0.1) and rhabdoid variant histology (HR 1.5, p=0.1) showed higher cancer specific mortality than clear cell renal cell carcinoma. No cancer specific mortality differences were recorded for mesenchymal, neuroendocrine and mucinous tubular and spindle cell variant histology. In nephrectomy subgroup higher cancer specific mortality was recorded after partial nephrectomy than radical nephrectomy in sarcomatoid variant histology after inverse probability treatment weighting and multivariate adjustment (HR 1.2, p=0.02). CONCLUSIONS: TNM stage at diagnosis is universally more advanced in patients with variant histology, except for mucinous tubular and spindle cell. Cancer specific mortality is higher in collecting duct, sarcomatoid, rhabdoid and renal medullary variant histology, but not in other variant histology. Partial nephrectomy is associated with worse survival in sarcomatoid variant histology but could not be assessed in other variant histology due to small sample size.

Conditional Survival of Patients With Nonmetastatic Renal Cell Carcinoma: How Cancer-Specific Mortality Changes After Nephrectomy.

BACKGROUND: Conditional survival (CS) may reveal important differences in cancer-specific mortality (CSM) among patients with nonmetastatic renal cell carcinoma (nmRCC). This study assessed CS according to T and N stages in patients treated surgically for nmRCC. PATIENTS AND METHODS: Within the SEER database (2001-2015), all patients with nmRCC treated with either partial or radical nephrectomy were identified. CSM-free estimates according to T and N stage and substage groupings (pT1aN0-pT4N0 and pTanyN1) and multivariable Cox regression models with adjustment for Fuhrman grade and histologic subtype were assessed. RESULTS: According to T and N stage and substage groupings, the following patients were included in the study: 35,966 (46.2%) with pT1aN0 disease; 18,858 (24.2%) with pT1bN0; 5,977 (7.7%) with pT2aN0; 2,511 (3.2%) with pT2bN0; 11,839 (15.2%) with pT3aN0; 1,037 (1.3%) with pT3b-cN0; 402 (0.5%) with pT4N0; and 1,302 (1.7%) with pTanyN1. Conditional CSM-free survival estimates were 98.2% at 1 year versus 98.0% at 10 years of event-free follow-up for patients with pT1aN0 disease, relative to baseline. Conversely, pT4N0/pTanyN1 conditional CSM-free survival estimates were 55.8% at 1 year versus 77.9% at 8 years of event-free follow-up. Attrition due to mortality was highest in patients with pT4N0/pTanyN1 disease. In multivariable Cox regression analyses, T stage, tumor grade, and histologic subtype represented independent predictors, but no interactions were identified. CONCLUSIONS: Tumor stage and its substages represent extremely important determinants of prognosis after lengthy event-free follow-up. The recorded observations have critical importance for physicians regarding patient follow-up and counseling.

Prostate Cancer Grade and Stage Misclassification in Active Surveillance Candidates: Black Versus White Patients.

BACKGROUND: Misclassification rates defined as upgrading, upstaging, and upgrading and/or upstaging have not been tested in contemporary Black patients relative to White patients who fulfilled criteria for very-low-risk, low-risk, or favorable intermediate-risk prostate cancer. This study aimed to address this void. METHODS: Within the SEER database (2010-2015), we focused on patients with very low, low, and favorable intermediate risk for prostate cancer who underwent radical prostatectomy and had available stage and grade information. Descriptive analyses, temporal trend analyses, and multivariate logistic regression analyses were used. RESULTS: Overall, 4,704 patients with very low risk (701 Black vs 4,003 White), 17,785 with low risk (2,696 Black vs 15,089 White), and 11,040 with favorable intermediate risk (1,693 Black vs 9,347 White) were identified. Rates of upgrading and/or upstaging in Black versus White patients were respectively 42.1% versus 37.7% (absolute Δ = +4.4%; P<.001) in those with very low risk, 48.6% versus 46.0% (absolute Δ = +2.6%; P<.001) in those with low risk, and 33.8% versus 35.3% (absolute Δ = -1.5%; P=.05) in those with favorable intermediate risk. CONCLUSIONS: Rates of misclassification were particularly elevated in patients with very low risk and low risk, regardless of race, and ranged from 33.8% to 48.6%. Recalibration of very-low-, low-, and, to a lesser extent, favorable intermediate-risk active surveillance criteria may be required. Finally, our data indicate that Black patients may be given the same consideration as White patients when active surveillance is an option. However, further validations should ideally follow.

Contemporary North-American population-based validation of the International Germ Cell Consensus Classification for metastatic germ cell tumors of the testis.

BACKGROUND: The International Germ Cell Consensus Classification (IGCCC) is the recommended stratification scheme for newly diagnosed metastatic seminoma (mSGCT) and non-seminoma germ cell tumor (mNSGCT) patients. However, a contemporary North-American population-based validation has never been completed and represented our focus. MATERIALS AND METHODS: We identified mSGCT and mNSGCT patients within the SEER database (2004-2015). The IGCCC criteria were used for stratification into prognostic groups. Kaplan-Meier (KM) derived actuarial 5-year overall survival (OS) rates were calculated. In addition, cumulative incidence plots tested cancer-specific (CSM) and other-cause mortality (OCM) rates. RESULTS: Of 321 mSGCT patients, 190 (59.2%) and 131 (40.8%), respectively, fulfilled good and intermediate prognosis criteria. Of 803 mNSGCT patients, 209 (26.1%), 100 (12.4%), and 494 (61.5%), respectively, fulfilled good, intermediate, and poor prognosis criteria. In mSGCT patients, actuarial KM derived 5-year OS was 87% and 78% for, respectively, good and intermediate prognosis groups (p = 0.02). In cumulative incidence analyses, statistically significant differences were recorded for CSM but not for OCM between good versus intermediate prognosis groups. In mNSGCT patients, actuarial KM derived 5-year OS was 89%, 75% and 60% for, respectively, good, intermediate, and poor prognosis groups (p < 0.001). In cumulative incidence analyses, statistically significant differences were recorded for both CSM and OCM between good, intermediate, and poor prognosis groups. CONCLUSIONS: Our findings represent the first population-based validation of the IGCCC in contemporary North-American mSGCT and mNSGCT patients. The recorded OM rates closely replicate those of the original publication, except for better survival of poor prognosis mNSGCT patients.

Survival of contemporary patients with non-metastatic urachal vs. non-urachal adenocarcinoma of the urinary bladder.

PURPOSE: To test the effect of tumor location (urachal vs. non-urachal) on cancer-specific mortality (CSM) in patients with adenocarcinoma of the urinary bladder (ADKUB). MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results registry (2004-2016), we identified patients with non-metastatic (≤ T4N0M0) ADKUB. Stratification was made according to tumor location: urachal vs. non-urachal ADKUB. Kaplan-Meier plots and multivariable Cox regression models were fitted before and after 1:3 propensity score (PS) matching and separate Cox regression models were refitted before and after inverse probability of treatment weighting (IPTW). RESULTS: Of 1681 patients, 226 (13.5%) vs. 1455 (86.5%) harboured urachal vs. non-urachal ADKUB, respectively. Five-year cancer-specific survival (CSS) rates were, respectively, 75 vs. 67% for urachal vs. non-urachal ADKUB (p = 0.001). In subgroup analyses of ≤ T2N0M0 patients, 5-year CSS rates were, respectively, 84 vs. 73% for urachal vs. non-urachal ADKUB (p = 0.006). In subgroup analyses of T3-4N0M0 patients, 5-year CSS rates were, respectively, 68 vs. 49% for urachal vs. non-urachal ADKUB (p < 0.001). In multivariable Cox regression models, urachal ADKUB was associated with lower CSM rates (HR 0.6; p = 0.01). Virtually, the same findings were recorded after 1:3 PS matching (HR 0.6; p = 0.009) as well as when Cox regression models were refitted after IPTW (HR 0.7; p = 0.01). CONCLUSION: The distinction between urachal vs. non-urachal ADKUB indicates better prognosis when the origin of the tumor is urachal, regardless of methodological approach used for the comparison.

Conditional survival of patients with stage I-III squamous cell carcinoma of the penis: temporal changes in cancer-specific mortality.

PURPOSE: To test the conditional survival that examined the effect of event-free survival on cancer-specific mortality after primary tumour excision (PTE) in patients with squamous cell carcinoma of the penis (SCCP). MATERIALS AND METHODS: Within the SEER database (1998-2015), 2282 stage I-III SCCP patients were identified. Conditional survival estimates were used to calculate cancer-specific mortality (CSM) after event-free survival intervals of 1, 2, 3, and 5 years. Multivariable Cox regression models predicted CSM according to event-free survival. RESULTS: After PTE, 5-year CSM-free rate was 78.0% and increased to 84.6%, 88.1%, 92.0%, and 94.2% in patients who survived ≥ 1, ≥ 2, ≥ 3, and ≥ 5 years. After stratification according to tumour characteristics, 5-year CSM-free rates increased from 85.9 to 95.4%, 79.0 to 97.1%, 78.9 to 90.0%, and from 54.5 to 86.0% in those survived ≥ 5 years, respectively, in T1N0, T2N0, T3N0, and N1-2 patients. In multivariable analyses, T2N0 [hazard ratio (HR) 1.68; p value < 0.001], T3N0 (HR 1.94; p value 0.001), and N1-2 (HR 6.61; p value < 0.001) were independent predictors of higher CSM rate at baseline, relative to T1N0. A decrease in all HRs was assessed over time in patients who survived. Attrition due to CSM was highest in N1-2 cohort and lowest in T1N0. CONCLUSIONS: Conditional survival models showed a direct relationship between event-free survival duration and subsequent CSM in SCCP patients. Even patients with non-organ-confined disease may achieve survival probabilities similar to those with organ-confined disease after at least 5 years of event-free survival since PTE.

Partial versus radical nephrectomy in very elderly patients: a propensity score analysis of surgical, functional and oncologic outcomes (RESURGE project).

PURPOSE: To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor. PATIENTS AND METHODS: A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM). RESULTS: A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p < 0.01). PN was not correlated with OM (HR = 0.71; p = 0.56), OCM (HR = 0.74; p = 0.5), and showed a protective trend for CSM (HR = 0.19; p = 0.05). PN was found to be a protective factor for surgical CKD (HR = 0.28; p < 0.01) and worsening of eGFR in patients with baseline CKD. Retrospective design represents a limitation of this analysis. CONCLUSIONS: Adoption of PN in very elderly patients with localized renal tumor does not compromise oncological outcomes, and it allows better functional preservation at mid-term (3-year) follow-up, relative to RN. Whether this functional benefit translates into a survival benefit remains to be determined.

Assessment of other-cause mortality in localized renal cell carcinoma patients within 15 years: A population-based analysis.

BACKGROUND AND OBJECTIVE: Five-year other cause mortality (OCM) after nephrectomy for non-metastatic renal cell carcinoma (RCC) should be marginal in properly selected surgical candidates. We examined 5-year OCM rates as a quality of care indicator for patient selection. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (1997-2011), we identified 59267 RCC patients treated with either radical (n = 27 804, 46.9%) or partial nephrectomy (n = 31 463, 53.1%). Temporal trends and multivariable Cox regression analyses assessed 5-year OCM. Data were stratified according to age group, year of diagnosis, race, marital status, gender, and socio-economic status. The overall OCM rates for the entire cohort at 5 years of follow-up was 4.7% and decreased from 9.4% to 5.6% over the study span (-3.8%, P < .001). The greatest decrease in 5-year OCM rates over time was recorded in patients >70 years (17.0%-9.6%, slope, -0.6%/y), as well as in African-Americans (12.0-6.2%; slope, -0.3%/y) and in males (8.9%-4.7%; slope, -0.3%, all P < .001). CONCLUSIONS: An important OCM decrease was recorded over the study span. Nonetheless, further improvement may be accomplished, especially in African-Americans, unmarried and older individuals, who exhibited higher OCM rates than others. These three groups may represent ideal targets for better patient selection based on OCM considerations.

Preoperative frailty predicts adverse short-term postoperative outcomes in patients treated with radical nephroureterectomy.

BACKGROUND: To investigate the effect of frailty on short-term postoperative outcomes and total hospital charges (THCs) in patients with non-metastatic upper urinary tract carcinoma, treated with radical nephroureterectomy (RNU). METHODS: Within the National Inpatient Sample (NIS) database we identified 11 258 RNU patients (2000-2015). We used the Johns Hopkins frailty-indicator to stratify patients according to frailty status. Time trends and multivariable logistic, Poisson and linear regression models were applied. RESULTS: Overall, 1801 (16.0%) patients were frail, 4664 (41.4%) were older than 75 years and 1530 (13.6%) had Charlson comorbidity index ≥2. Rates of frail patients increased over time, from 7.3% to 24.9% (P < .001). Frail patients exhibited higher rates (all P < .05) of overall complications (62.6% vs 50.9%), in-hospital mortality (1.6% vs 1.0%), non-home-based discharge (22.7% vs 12.1%), longer length of stay (LOS) (6 vs 1 day) and higher THCs ($49 539 vs $39 644). Moreover, frailty independently predicted (all P < .05) overall complications (OR, 1.46), in-hospital mortality (OR, 1.52), non-home-based discharge (OR, 1.36), longer LOS (RR, 1.30) and higher THCs (RR, +$11 806). CONCLUSION: Preoperative frailty is important in RNU patients. One of four RNU patients is frail. Moreover, frailty predicts short-term postoperative complications, as well as longer LOS and higher THCs after RNU.

Contemporary conditional cancer-specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract.

BACKGROUND AND OBJECTIVES: To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. RESULTS: Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. CONCLUSIONS: A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

Rates of other-cause mortality after radical cystectomy are decreasing over time-A population-based analysis over two decades.

BACKGROUND AND OBJECTIVES: To investigate other-cause mortality (OCM) rates over time according to several baseline characteristics in bladder cancer (BCa) patients treated with radical cystectomy (RC). METHODS: Within the Surveillance, Epidemiology, and End Results database (1988-2011), we identified 7702 T1-2 N0 M0 urothelial BCa patients treated with RC. Temporal trends and multivariable Cox regression (MCR) analyses assessed 5-year OCM. Data were stratified according to the year of diagnosis (1988-1995 vs 1996-2000 vs 2001-2004 vs 2005-2008 vs 2009-2011), age group (<60 vs 60-75 vs >75 years), sex, race, marital status, and socioeconomic status. RESULTS: Overall, OCM rates decreased from 13.9% in 1988-1995 to 8.6% in 2009-2011. The greatest decrease was recorded in elderly (>75) patients (32%-16%, slope: -0.55% per year; P = .01), followed by patients aged 60 to 75 (21%-5%, slope: -0.35% per year; P = .01), unmarried patients (16%-10%, slope: -0.26% per year; P < .001), male patients (14%-8.9%, slope: -0.23% per year), and African Americans (16%-11%, slope: -0.27% per year; P < .001). MCR models corroborated these results. CONCLUSIONS: Most important decrease in OCM after RC over the last decades was recorded in the elderly, unmarried, and male patients. Nonetheless, these three patient groups still represent ideal targets for efforts aimed at minimizing the morbidity and mortality after RC, as their risk of OCM is higher than in others.

Adherence to guideline recommendations for multimodality treatment of patients with pT2-3 M0 non-urothelial carcinoma of the urinary bladder: Temporal trends and survival outcomes.

OBJECTIVES: To analyze contemporary multimodality treatment rates, defined as radical cystectomy plus chemotherapy and/or radiotherapy, for pT2-3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients. Additionally, we tested for the effect of multimodality treatment versus radical cystectomy alone on cancer-specific mortality. METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 887 pT2-3 any N-stage M0 non-urothelial carcinoma of urinary bladder patients treated with radical cystectomy were identified. Kaplan-Meier plots, and univariable and multivariable Cox regression analyses focused on cancer-specific mortality rates. RESULTS: Squamous cell carcinoma was recorded in 499 (56.3%) patients, neuroendocrine carcinoma in 246 (27.7%) and adenocarcinoma in 142 (16.0%). The highest proportion of multimodality treatment patients was recorded in neuroendocrine carcinoma (69.1%), relative to adenocarcinoma (34.5%) and squamous cell carcinoma (26.4%). A statistically significant annual increase was recorded in multimodality treatment rates in neuroendocrine carcinoma patients (46.7-74.2%, P < 0.01), but not in adenocarcinoma or squamous cell carcinoma patients. The 5-year cancer-specific mortality rate in neuroendocrine carcinoma patients was significantly lower after multimodality treatment versus radical cystectomy alone (37.0% vs 51.5%; P < 0.01), but no statistically significant differences were recorded in both adenocarcinoma (46.1% vs 35.5%; P = 0.8) and squamous cell carcinoma (41.4% vs 31.1%; P = 0.8) patients. In multivariable analyses, for neuroendocrine carcinoma patients, multimodality treatment was an independent predictor of a lower cancer-specific mortality rate (hazard ratio 0.58, P = 0.03). CONCLUSIONS: Multimodality treatment has been increasingly used during the study period in neuroendocrine carcinoma patients, and it has translated into a cancer-specific mortality benefit. This is not the case for other non-urothelial carcinoma of urinary bladder patients, such as adenocarcinoma or squamous cell carcinoma.

Cryoablation Predisposes to Higher Cancer Specific Mortality Relative to Partial Nephrectomy in Patients with Nonmetastatic pT1b Kidney Cancer.

PURPOSE: Cryoablation is done in select patients with pT1b nonmetastatic renal cell carcinoma without convincing proof of efficacy. Our aim was to test for differences in the cancer specific mortality rate for cryoablation and partial nephrectomy in T1b nonmetastatic renal cell carcinoma cases. MATERIALS AND METHODS: In the 2004 to 2015 SEER (Surveillance, Epidemiology, and End Results) database we identified 5,763 patients with a T1b tumor treated with cryoablation or partial nephrectomy. Modeling relied on multivariable logistic regression models predicting cryoablation vs partial nephrectomy. After 1:2 ratio propensity score matching between patients treated with cryoablation vs partial nephrectomy we used cumulative incidence plot and competing risks regression to test differences in cancer specific mortality and other cause mortality rates. RESULTS: Relative to the 5,521 patients who underwent partial nephrectomy the 242 treated with cryoablation were older, had smaller tumors and more frequently harbored unclassified renal cell carcinoma of low or unknown grade. Median followup was 38 months. In multivariable logistic regression models predicting cryoablation vs partial nephrectomy more advanced patient age was an independent predictor (OR 1.03; p=0.007). After propensity score matching and other cause mortality adjustment the 5-year cancer specific mortality rate was 2.5-fold higher after cryoablation than after partial nephrectomy (p=0.03). Conversely after propensity score matching and cancer specific mortality adjustment the 5-year other cause mortality rate was similar to that of partial nephrectomy after cryoablation (HR 1.45, p=0.12). The major limitation of this study was the lack of recurrence and metastatic progression data. CONCLUSIONS: The current findings demonstrated a 2.5-fold increase in cancer specific mortality when cryoablation was performed in patients with pT1b renal cell carcinoma. This observation should be interpreted as a contraindication to cryoablation outside clinical trials or institutional protocols.