A panel of systemic inflammatory response biomarkers for outcome prediction in patients treated with radical cystectomy for urothelial carcinoma.

OBJECTIVES: To determine the predictive and prognostic value of a panel of systemic inflammatory response (SIR) biomarkers relative to established clinicopathological variables in order to improve patient selection and facilitate more efficient delivery of peri-operative systemic therapy. MATERIALS AND METHODS: The preoperative serum levels of a panel of SIR biomarkers, including albumin-globulin ratio, neutrophil-lymphocyte ratio, De Ritis ratio, monocyte-lymphocyte ratio and modified Glasgow prognostic score were assessed in 4199 patients treated with radical cystectomy for clinically non-metastatic urothelial carcinoma of the bladder. Patients were randomly divided into a training and a testing cohort. A machine-learning-based variable selection approach (least absolute shrinkage and selection operator regression) was used for the fitting of several multivariable predictive and prognostic models. The outcomes of interest included prediction of upstaging to carcinoma invading bladder muscle (MIBC), lymph node involvement, pT3/4 disease, cancer-specific survival (CSS) and recurrence-free survival (RFS). The discriminatory ability of each model was either quantified by area under the receiver-operating curves or by the C-index. After validation and calibration of each model, a nomogram was created and decision-curve analysis was used to evaluate the clinical net benefit. RESULTS: For all outcome variables, at least one SIR biomarker was selected by the machine-learning process to be of high discriminative power during the fitting of the models. In the testing cohort, model performance evaluation for preoperative prediction of lymph node metastasis, ≥pT3 disease and upstaging to MIBC showed a 200-fold bootstrap-corrected area under the curve of 67.3%, 73% and 65.8%, respectively. For postoperative prognosis of CSS and RFS, a 200-fold bootstrap corrected C-index of 73.3% and 72.2%, respectively, was found. However, even the most predictive combinations of SIR biomarkers only marginally increased the discriminative ability of the respective model in comparison to established clinicopathological variables. CONCLUSION: While our machine-learning approach for fitting of the models with the highest discriminative ability incorporated several previously validated SIR biomarkers, these failed to improve the discriminative ability of the models to a clinically meaningful degree. While the prognostic and predictive value of such cheap and readily available biomarkers warrants further evaluation in the age of immunotherapy, additional novel biomarkers are still needed to improve risk stratification.

Prognostic factors in patients with small renal masses: a comparison between <2 vs. 2.1-4 cm renal cell carcinomas.

BACKGROUND: Few data factually support the prognostic distinction between renal cell carcinomas (RCC) < 2 vs. 2.1-4 cm, in terms of cancer-specific mortality (CSM). We investigated CSM rates over time in <2 vs. 2.1-4 cm RCC, according to patient and tumor characteristics. METHODS: Within the Surveillance, Epidemiology and End Results (SEER) database, we focused on patients with T1aN0M0 RCC who underwent either radical or partial nephrectomy between 2000 and 2015. Temporal trends, Kaplan-Meier plots and multivariable Cox-regression analyses assessed CSM. RESULTS: Of 43,147 T1aN0M0 patients, 12,238 (28.4%) harbored RCC < 2 cm and 30,909 (71.6%) 2.1-4 cm RCC. The distribution of histological subtypes according to 2 cm cut-off was as follows: a). clear-cell G1/G2: 64.5 vs. 61.8%; b). papillary G1/G2 15.9 vs. 11.1%; c). clear-cell G3/G4: 9.9 vs. 16.1%; d). papillary G3/G4 4.9 vs. 5.4%; and e). chromophobe 4.9 vs. 5.2%. Five-year CSM rates were invariably lower in RCC < 2 cm than in 2.1-4 cm, for all histological subtypes and grade groups (a-e), even after additional multivariable adjustment for age and residual tumor size differences. 5-year CSM rates improved in more contemporary years, in both tumor size groups (< 2 vs. 2.1-4 cm), but to a greater extent in 2.1-4 cm renal masses. CONCLUSION: Our results validate the presence of prognostically more favorable CSM outcomes in RCC < 2 cm vs. 2.1-4 cm, across all histological subtypes and grades. Moreover, temporal improvements were also recorded in both <2 and 2.1-4 cm RCC groups, with more pronounced improvements in patients with 2.1-4 cm renal masses. However, prospective randomized trials are needed to further confirm our results.

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.

The Risk of New Onset Dementia and/or Alzheimer Disease among Patients with Prostate Cancer Treated with Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

PURPOSE: Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I2 statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months). RESULTS: A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months). CONCLUSIONS: Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.

The recurrence and progression risk after simultaneous endoscopic surgery of urothelial bladder tumour and benign prostatic hyperplasia: a systematic review and meta-analysis.

OBJECTIVES: To evaluate recurrence and progression risk after simultaneous endoscopic surgery of bladder cancer and benign prostatic hyperplasia (BPH), as simultaneous surgery is not an unusual scenario and theoretically simultaneous transurethral resection of bladder tumour (TURBT) and transurethral resection of the prostate (TURP) can lead to an increased risk of recurrence in the bladder neck and prostatic urethra (BN/PU). METHODS: We conducted a systematic review and meta-analysis to assess the risk of recurrence (i.e. whole bladder and/or BN/PU) and tumour progression as outcomes after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone. We queried PubMed and Web of Science database on 1 January 2020. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to the I2 statistic, respectively. RESULTS: Nine retrospective and three clinical trial studies were selected after considering inclusion and exclusion criteria. We conducted the meta-analysis on retrospective and randomised controlled trials (RCTs) separately. Eight retrospective and three RCT studies were included to assess the BN/PU recurrence risk and the summarised risk ratio (RR) was 1.02 (95% confidence interval [CI] 0.74-1.41) and 0.93 (95% CI 0.47-1.84), respectively. Five retrospective and two RCT studies were included to assess the progression risk and the summarised RR was 0.91 (95% CI 0.56-1.48) and 1.16 (95% CI 0.30-4.51), respectively. Eight retrospective and three RCT studies were included to assess the whole bladder recurrence risk and the summarised RR was 0.87 (95% CI 0.78-0.97) and 0.89 (95% CI 0.65-1.21), respectively. CONCLUSION: We did not observe any increased risk of total bladder recurrence, BN/PU recurrence, or progression after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone.

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.

PSA, stage, grade and prostate cancer specific mortality in Asian American patients relative to Caucasians according to the United States Census Bureau race definitions.

BACKGROUND: The United States Census Bureau recommends distinguishing between "Asians" vs. "Native Hawaiians or Other Pacific Islanders" (NHOPI). We tested for prognostic differences according to this stratification in patients with prostate cancer (PCa) of all stages. METHODS: Descriptive statistics, time-trend analyses, Kaplan-Meier plots and multivariate Cox regression models were used to test for differences at diagnosis, as well as for cancer specific mortality (CSM) according to the Census Bureau's definition in either non-metastatic or metastatic patients vs. 1:4 propensity score (PS)-matched Caucasian controls, identified within the Surveillance, Epidemiology and End Results database (2004-2016). RESULTS: Of all 380,705 PCa patients, NHOPI accounted for 1877 (0.5%) vs. 23,343 (6.1%) remaining Asians vs. 93.4% Caucasians. NHOPI invariably harbored worse PCa characteristics at diagnosis. The rates of PSA ≥ 20 ng/ml, Gleason ≥ 8, T3/T4, N1- and M1 stages were highest for NHOPI, followed by Asians, followed by Caucasians (PSA ≥ 20: 18.4 vs. 14.8 vs. 10.2%, Gleason ≥ 8: 24.9 vs. 22.1, vs. 15.9%, T3/T4: 5.5 vs. 4.2 vs. 3.5%, N1: 4.4 vs. 2.8, vs. 2.7%, M1: 8.3 vs. 4.9 vs. 3.9%). Despite the worst PCa characteristics at diagnosis, NHOPI did not exhibit worse CSM than Caucasians. Moreover, despite worse PCa characteristics, Asians exhibited more favorable CSM than Caucasians in comparisons that focussed on non-metastatic and on metastatic patients. CONCLUSIONS: Our observations corroborate the validity of the distinction between NHOPI and Asian patients according to the Census Bureau's recommendation, since these two groups show differences in PSA, grade and stage characteristics at diagnosis in addition to exhibiting differences in CSM even after PS matching and multivariate adjustment.

Holmium laser enucleation of the prostate: efficacy, safety and preoperative management in patients presenting with anticoagulation therapy.

PURPOSE: We evaluated efficacy and safety profile of patients with anticoagulation therapy (AT) undergoing holmium laser enucleation of the prostate (HoLEP). METHODS: Within our prospective institutional database (11/2017 to 11/2019), we analyzed functional outcomes and 30-day complication rates of HoLEP patients according to Clavien-Dindo classification (CLD), stratified according to specific AT vs. no AT. Further analyses consisted of uni- and multivariate logistic regression models (LRM) predicting complications. RESULTS: Of 268 patients undergoing HoLEP, 104 (38.8%) received AT: 25.7% were treated with platelet aggregation inhibitors (PAI), 8.2% with new oral anticoagulants (NOAC) and 4.9% with AT-combinations or coumarins bridged with low molecular weight heparins (LMWH/combination). Patients receiving AT were significantly more comorbid (p < 0.01). Pre- and postoperative maximal flow rates, residual void urine and IPSS at 3 months after surgery were invariably improved after HoLEP for patients with/ without AT. Overall complication rate was 19.5% in patients with no AT vs. 26.1% vs. 27.3 vs. 46.2%, respectively, in patients with PAI, NOAC and LMWH/combination (p < 0.01). Major complications (CLD ≥ 3b) occurred in 6.1% of no AT patients vs. 4.3% vs. 4.5 vs. 0% in patients with PAI, NOAC and LMWH/combination, respectively (p < 0.01). In multivariate LRM, AT was not significantly associated with higher complication rates, whereas high ASA status (OR 2.2, p = 0.04), age (OR 1.04, p = 0.02) and bioptical or incidental prostate cancer (OR 2.5, p = 0.01) represented independent risk factors. CONCLUSION: Despite higher overall complication rates in AT patients, major complications were not more frequent in AT patients. HoLEP is safe and effective in anticoagulated patients.

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.

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.

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.

Prognostic value of the preoperative albumin-globulin ratio in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

OBJECTIVE: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort. MATERIALS AND METHODS: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints. RESULTS: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024). CONCLUSIONS: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery.

The impact of sex and age on distribution of metastases in patients with renal cell carcinoma.

BACKGROUND: Our objective was to investigate age and sex-related discrepancies on distribution of metastases in patients with metastatic renal cell carcinoma (RCC). METHODS: Within the National Inpatient Sample database (2008-2015) we identified 9607 patients with metastatic RCC. Trend test and Chi-square test analyses were used to evaluate the relationship between age and site of metastases, according to sex. RESULTS: Of 9607 patients with metastatic RCC, 6344 (65.9%) were men and 3263 (34.1%) were women. Thoracic, abdominal, bone and brain metastases were present in 51.1 vs. 52.8%, 42.6 vs. 44.3%, 29.9 vs. 29.2% and 8.6 vs. 8.8% of men vs. women, respectively. Increasing age was associated with decreasing rates of thoracic (from 55.5 to 48.5%) and brain (from 8.6 to 5.8%) metastases in men and with decreasing rates of abdominal (from 48.3 to 39.6%), bone (from 32.6 to 24.9%) and brain (from 8.8 to 5.4%) metastases in women. (all p < 0.05). Rates of concomitant metastatic sites also decreased with increasing age, from 57.1 to 50.8% in men and from 54.1 to 50.2% in women. CONCLUSIONS: Important age and sex-related differences exist in the distribution of RCC metastases. The distribution of metastases is marginally different between sexes. Specifically, more advanced age is associated with lower rates of thoracic and brain metastases in men and with lower rates of abdominal, bone and brain metastases in women. Age and sex should be take into consideration into the staging management strategy, as well as into the follow-up strategy of patients with metastatic RCC.

Higher Cancer Mortality in Rural Upper Urinary Tract Urothelial Carcinoma Patients.

OBJECTIVE: The aim of the study was to investigate differences in the stage at presentation and cancer-specific mortality (CSM) between rural area (RA) and urban area (UA) residence status in nonmetastatic upper urinary tract urothelial carcinoma (UTUC) patients. METHODS: Newly diagnosed T1-3N0M0 UTUC patients with available residence status were abstracted from the Surveillance, Epidemiology, and End Results database (2004-2016). Propensity score (PS) matching (1 RA vs. 3 UA) accounted for age (interval ≤2 years), T stage (exact matching: T1, T2, and T3), and tumor grade (exact matching: high grade, low grade/unknown). Cumulative incidence plots and multivariable competing risk regression models focused on CSM, after adjustment for other-cause mortality. RESULTS: Of 6,012 patients, 125 (2.1%) resided in RAs and 5,887 (97.9%) in UAs. RA patients were younger than UA patients (median age 72 vs. 75 years, p = 0.03). No differences were recorded in tumor location, T stage, tumor grade, or surgical treatment between RA and UA patients. After 1:3 PS matching, 125 RA patients and 375 UA patients were assessable. At 5 years of follow-up, CSM rates were 26.7 versus 15.7% according to RA versus UA, respectively. After additional multivariable adjustment for age, sex, tumor location, and surgical treatment, RA remained an independent predictor of higher CSM (hazard ratio 1.75, p = 0.02). CONCLUSIONS: Despite no differences in cancer characteristics, UTUC patients in RA are at higher risk of CSM than their UA counterparts. This suggests suboptimal care delivery and compliance as possible causes. Complex and/or rare disease should be centralized to expert centers, which are often in UAs.

Radical prostatectomy improves survival in selected metastatic prostate cancer patients: A North American population-based study.

OBJECTIVE: To test whether radical prostatectomy might result in better survival than external beam radiation therapy in metastatic prostate cancer patients. METHODS: Newly diagnosed metastatic prostate cancer patients with M1a/b substages, treated with radical prostatectomy or external beam radiation therapy were abstracted from the Surveillance, Epidemiology and End Results database (2004-2016). Temporal trend analyses, propensity score matching, cumulative incidence plots, multivariate competing risks regression models and landmark analyses were used. RESULTS: Of 4280 patients, 954 (22.3%) were treated with radical prostatectomy. After propensity score matching, 5-year cancer-specific mortality was 47.0 versus 53.0% in radical prostatectomy versus external beam radiation therapy patients (P = 0.003). In propensity score matched competing risks regression models, radical prostatectomy was associated with lower cancer-specific mortality versus external beam radiation therapy (hazard ratio 0.79, 95% confidence interval 0.79-0.90; P = 0.001). Finally, landmark analyses rejected the bias favoring radical prostatectomy. Finally, in subgroup analyses, we relied on selection criteria that most closely resembled the STAMPEDE criteria and a similar hazard ratio of 0.8 (P < 0.001) was recorded. CONCLUSION: In metastatic prostate cancer, radical prostatectomy results in lower cancer-specific mortality relative to external beam radiation therapy. Even after adjustment for age at diagnosis, prostate-specific antigen and biopsy Gleason grade grouping, lower cancer-specific mortality rates are recorded in radical prostatectomy patients than in external beam radiation therapy patients. As a result, radical prostatectomy should be considered as a treatment option in selected metastatic prostate cancer patients. However, further validation will be provided by ongoing clinical trials.

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.

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.

The Impact of Race and Age on Distribution of Metastases in Patients with Prostate Cancer.

PURPOSE: We investigated the effect of race and age on the distribution of prostate cancer metastases. MATERIALS AND METHODS: Records for patients with metastatic prostate cancer were abstracted from the National Inpatient Sample database (2008-2015). RESULTS: Of 6,963 patients with metastatic prostate cancer 3,881 (72.2%) were Caucasian and 1,494 (27.8%) were African American. Bone metastases were the most common site of metastases in Caucasian and African American patients (83.9% and 87.0%, respectively), followed by distant lymph node metastases in Caucasian (13.9% of Caucasian vs 13.2% of African American), liver metastases in African American (13.8% of African American vs 13.3% of Caucasian) and lung metastases in Caucasian and African American patients (9.3% and 13.1%, respectively). No clinically meaningful differences were recorded in age and race analyses, except for lymph node metastases (61.1% to 23.4% in Caucasian vs 39.0% to 25.1% in African American patients), which decreased with age. Specific single organ metastatic sites, outside of bone and lymph nodes, were low in both racial groups (2.1% or less). The rate of brain metastases was also rare in both racial groups at 1.4% or less, regardless of other metastatic locations. Thoracic metastases, in the absence of bone and abdominal metastases, were present in 1.9% of Caucasian and African American patients. CONCLUSIONS: The most important finding according to age and race resided in rates of lymph node metastases. Conversely, all other racial and age related differences were subtle. Nonetheless, they are important in the context of planning and/or design of clinical trials. Finally, brain (1.4%) and thoracic (1.9%) metastases affect few patients and routine brain and chest imaging may not be warranted.

Small Renal Masses With Tumor Size 0 to 2 cm: A SEER-Based Study and Validation of NCCN Guidelines.

BACKGROUND: The NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer recommend active surveillance as an option for initial management of T1a 0- to 2-cm renal lesions, in addition to partial nephrectomy, radical nephrectomy, and focal ablation. However, contemporary data regarding the distribution of patient and renal cell carcinoma characteristics within this special patient group are scarce. METHODS: Within the SEER database (2002-2016), 13,364 patients with T1aNanyMany 0- to 2-cm renal lesions treated with nephrectomy were identified. Data were tabulated according to histologic subtype, Fuhrman grade (FG1-2 vs FG3-4), age category, and sex. In addition, rates of synchronous metastases were quantified. RESULTS: Overall, clear-cell (69.3%), papillary (21.4%), chromophobe (6.9%), multilocular cystic (2.0%), sarcomatoid dedifferentiation (0.2%), and collecting-duct histologic subtypes (0.2%) were identified. Advanced age was associated with a lower rate of FG1-2 clear cell histologic subtype (70.8%-50.3%) but higher rates of FG1-2 papillary (11.1%-23.9%) and chromophobe histologic subtypes (6.2%-8.5%). Overall, 14.5% individuals harbored FG3-4 clear cell (9.8%) or FG3-4 papillary histologic subtypes (4.8%), and both were more prevalent in men. FG3-4 clear-cell and FG3-4 papillary histologic subtypes increased with age, more so in women than in men. The overall rate of synchronous metastases was 0.4% and ranged from 0 in the multilocular cystic subtype to 0.9% in the FG3-4 papillary histologic subtype, respectively, except for 13.8% in the sarcomatoid dedifferentiation histologic subtype. CONCLUSIONS: Most T1a 0- to 2-cm renal cell carcinoma represents the low-grade clear-cell or low-grade papillary histologic subtype, with an FG3-4 minority. Even in patients with the FG3-4 histologic subtype, rates of synchronous metastases are virtually zero.

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.