Differences in overall survival of penile cancer patients versus population-based controls.

PURPOSE: To assess whether 5-year overall survival (OS) of squamous cell carcinoma of the penis (SCCP) patients differs from age-matched male population-based controls. METHODS: We relied on the Surveillance Epidemiology and End Results database (2004-2018) to identify newly diagnosed (2004-2013) SCCP patients. For each case, we simulated an age-matched control (Monte Carlo simulation), relying on the Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS between SCCP patients and population-based controls in a stage-specific fashion. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) versus other-cause mortality (OCM). RESULTS: Of 2282 SCCP patients, the stage distribution was as follows: stage I 976 (43%) versus stage II 826 (36%) versus stage III 302 (13%) versus stage IV 178 (8%). At 5 years, OS of SCCP patients versus age-matched population-based controls was as follows: stage I 63% versus 80% (Δ = 17%), stage II 50% versus 80% (Δ = 30%), stage III 39% versus 84% (Δ = 45%), stage IV 26% versus 87% (Δ = 61%). At 5 years, CSM versus OCM in SCCP patients according to stage was as follows: stage I 12% versus 24%, stage II 22% versus 28%, stage III 47% versus 14%, and stage IV 60% versus 14%. CONCLUSION: SCCP patients exhibit worse OS across all stages. The difference in OS at 5 years between SCCP and age-matched male population-based controls ranged from 17% to 61%. At 5 years, CSM accounted for 12% to 60% of all deaths, across all stages.

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

BACKGROUND: It is unknown whether five-year overall survival (OS) differs and to what extent between testicular germ-cell tumor (TGCT) patients and age-matched male population-based controls. MATERIALS: We identified newly diagnosed (2004-2014) TGCT patients within Surveillance Epidemiology and End Results database 2004-2019. We compared OS between non-seminoma (NS-TGCT) and seminoma (S-TGCT) patients relative to age-matched male population-based controls based on Social Security Administration Life-Tables. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) vs. other-cause mortality (OCM). RESULTS: Of all 20,935 TGCT patients, 43% had NS-TGCT and 57% had S-TGCT. Of NS-TGCT patients, 63% were stage I vs. 16% stage II vs. 21% stage III. Of S-TGCT patients, 86% were stage I vs. 8% were stage II vs. 6% stage III. Five-year OS differences between NS-TGCT patients vs age-matched male population-based controls were 97 vs. 99% (Δ = 2%) for stage I, 96 vs. 99% (Δ = 3%) for stage II, 76 vs 98% (Δ = 22%) for stage III. Five-year OS differences between S-TGCT patients vs age-matched male population-based controls were 97 vs. 98% (Δ = 1%) for stage I, 95 vs. 97% (Δ = 2%) for stage II, 87 vs. 98% (Δ = 11%) for stage III. OCM rates ranged from 1 to 3% in NS-TGCT patients and from 2 to 4% in S-TGCT patients. CONCLUSION: The OS difference between NS-TGCT patients vs. age-matched male population-based controls was invariably higher across all stages (2-22%) than for S-TGCT patients (1-11%). Reassuringly, OCM rates were marginal in stage I and stage II patients. Conversely, higher OCM rates were recorded in stage III patients.

Assessment of the VENUSS and GRANT Models for Individual Prediction of Cancer-specific Survival in Surgically Treated Nonmetastatic Papillary Renal Cell Carcinoma.

Background: Guidelines recommend VENUSS and GRANT models for the prediction of cancer control outcomes after nephrectomy for nonmetastatic papillary renal cell carcinoma (pRCC). Objective: To test the ability of VENUSS and GRANT models to predict 5-yr cancer-specific survival in a North American population. Design setting and participants: For this retrospective study, we identified 4184 patients with unilateral surgically treated nonmetastatic pRCC in the Surveillance, Epidemiology, and End Results database (2004-2019). Outcome measurements and statistical analysis: The original VENUSS and GRANT risk categories were applied to predict 5-yr cancer-specific survival. A cross-validation method was used to test the accuracy and calibration of the models and to conduct decision curve analyses for the study cohort. Results and limitations: The VENUSS and GRANT categories represented independent predictors of cancer-specific mortality. On cross-validation, the accuracy of the VENUSS and GRANT risk categories was 0.73 and 0.65, respectively. Both models showed good calibration and performed better than random predictions in decision curve analysis. Limitations include the retrospective nature of the study and the absence of a central pathological review. Conclusion: VENUSS risk categories fulfilled prognostic model criteria for predicting cancer-specific survival 5 yr after surgery in North American patients with nonmetastatic pRCC as recommended by guidelines. Conversely, GRANT risk categories did not. Thus, VENUSS risk categories represent an important tool for counseling, follow-up planning, and patient selection for appropriate adjuvant trials in pRCC. Patient summary: We tested the ability of two validated methods (VENUSS and GRANT) to predict death due to papillary kidney cancer in a North American population. The VENUSS risk categories showed good performance in predicting 5-year cancer-specific survival.

Adenocarcinoma of the Bladder: Assessment of Survival Advantage Associated With Radical Cystectomy and Comparison With Urothelial Bladder Cancer.

PURPOSE: To evaluate the association between radical cystectomy (RC) and cancer-specific mortality (CSM) in patients diagnosed with adenocarcinoma of the bladder (ACB). Moreover, to directly compare the survival advantage of RC between ACB vs. urothelial bladder cancer (UBC). MATERIALS AND METHODS: Non-metastatic muscle-invasive ACB and UBC patients were identified within Surveillance, Epidemiology, and End Results database (SEER 2000-2018). All analyses were stratified between RC vs. no-RC, in either organ-confined (OC: T2N0M0) or non-organ-confined (NOC: T3-4N0M0 or TanyN1-3M0) stages. Propensity score matching (PSM), cumulative incidence plots, competing risks regression (CRR) analyses, and 3 months' landmark analyses were performed. RESULTS: Overall, 1,005 ACB and 47,741 UBC patients were identified, of whom 475 (47%) and 19,499 (41%) were treated with RC, respectively. After PSM, comparison between RC vs. no-RC applied to 127 vs. 127 OC-ACB, 7,611 vs. 7,611 OC-UBC, 143 vs. 143 NOC-ACB, and 4,664 vs. 4,664 NOC-UBC patients. 36-month CSM rates in RC vs. no-RC patients were 14 vs. 44% in OC-ACB, 18 vs. 39% in OC-UBC, 49 vs. 66% in NOC-ACB, and 44 vs. 56% in NOC-UBC patients. In CRR analyses, the effect of RC on CSM yielded a hazard ratio of 0.37 in OC-ACB, of 0.45 in OC-UBC, of 0.65 in NOC-ACB and of 0.68 in NOC-UBC patients (all P values<0.001). Landmark analyses virtually perfectly replicated the results. CONCLUSIONS: In ACB, regardless of stage, RC is associated with lower CSM. The magnitude of this survival advantage was greater in ACB than in UBC, even after control for immortal time bias.

Differences in overall survival of T2N0M0 bladder cancer patients vs. population-based controls according to treatment modalities.

PURPOSE: It is unknown to what extent overall survival (OS) of organ-confined (T2N0M0) urothelial carcinoma of the urinary bladder (UCUB) patients differs from age- and sex-matched population-based controls, especially when treatment modalities such as radical cystectomy (RC), trimodal therapy (TMT), or radiotherapy (RT) are considered. METHODS: Relying on the Surveillance Epidemiology and End Results database (2004-2018), we identified newly diagnosed (2004-2013) T2N0M0 UCUB patients treated with either RC, TMT or RT. For each case, we simulated an age- and sex-matched control (Monte Carlo simulation), relying on Social Security Administration Life Tables with 5 years of follow-up, and compared OS with that of RC-, TMT-, and RT-treated cases. Additionally, we relied on smoothed cumulative incidence plots to display cancer-specific mortality (CSM) and other-cause mortality (OCM) rates for each treatment modality. RESULTS: Of 7153 T2N0M0 UCUB patients, 4336 (61%) underwent RC, 1810 (25%) TMT, and 1007 (14%) RT. At 5 years, OS rate in RC cases was 65% vs. 86% in population-based controls (Δ = 21%); in TMT cases, 32% vs. 74% in population-based controls (Δ = 42%); and in RT, 13% vs. 60% in population-based control (Δ = 47%). Five-year CSM rates were highest in RT (57%), followed by TMT (46%) and RC (24%). Five-year OCM rates were the highest in RT (30%), followed by TMT (22%) and RC (12%). CONCLUSION: OS of T2N0M0 UCUB patients is substantially less than that of age- and sex-matched population-based controls. The biggest difference affects RT, followed by TMT. A modest difference was recorded in RC and population-based controls.

Differences in overall survival between clear cell metastatic renal cell carcinoma patients versus population-based controls according to race/ethnicity in the United States.

PURPOSE: To quantify differences in five-year overall survival (OS) between clear cell metastatic renal cell carcinoma (ccmRCC) patients and age- and sex-matched population-based controls, especially when race/ethnicity is considered. METHODS: We relied on the Surveillance, Epidemiology and End Results database (2006-2016) to identify newly diagnosed (2006- 2011) ccmRCC patients of either Caucasian, Hispanic, African American, or Asian/Pacific Islander race/ethnicity. For each case, we simulated an age- and sex-matched control (Monte Carlo simulation), relying on Social Security Administration Life Tables with five-year follow-up. We compared OS between ccmRCC patients and controls. Multivariable Cox regression models tested for race/ethnicity effect on OS. RESULTS: Of 3067 ccmRCC patients, 2167 (71%) were Caucasians vs. 488 (16%) Hispanics vs. 216 (7%) African Americans and 196 (6%) Asians/Pacific Islanders. At five years, OS difference between ccmRCC patients vs. population-based controls was greatest in African Americans (11 vs. 94%, Δ = 84%), followed by Hispanics (16 vs. 94%, Δ = 77%), Caucasians (16 vs. 89%, Δ = 73%) and Asians/Pacific Islanders (19 vs. 88%, Δ = 70%). In multivariable Cox regression models, African Americans exhibited highest Hazard Ratio for death (HR 1.3, p= 0.003). CONCLUSION: Relative to Life Tables' derived age- and sex-matched controls, ccmRCC patients exhibit drastically worse OS, especially African Americans.

Assessment of PSIM (Prostatic Systemic Inflammatory Markers) Score in Predicting Pathologic Features at Robotic Radical Prostatectomy in Patients with Low-Risk Prostate Cancer Who Met the Inclusion Criteria for Active Surveillance.

BACKGROUND: circulating levels of lymphocytes, platelets and neutrophils have been identified as factors related to unfavorable clinical outcome for many solid tumors. The aim of this cohort study is to evaluate and validate the use of the Prostatic Systemic Inflammatory Markers (PSIM) score in predicting and improving the detection of clinically significant prostate cancer (csPCa) in men undergoing robotic radical prostatectomy for low-risk prostate cancer who met the inclusion criteria for active surveillance. METHODS: we reviewed the medical records of 260 patients who fulfilled the inclusion criteria for active surveillance. We performed a head-to-head comparison between the histological findings of specimens after radical prostatectomy (RP) and prostate biopsies. The PSIM score was calculated on the basis of positivity according to cutoffs (neutrophil-to-lymphocyte ratio (NLR) 2.0, platelets-to-lymphocyte ratio (PLR) 118 and monocyte-to-lymphocyte-ratio (MLR) 5.0), with 1 point assigned for each value exceeding the specified threshold and then summed, yielding a final score ranging from 0 to 3. RESULTS: median NLR was 2.07, median PLR was 114.83, median MLR was 3.69. CONCLUSION: we found a significantly increase in the rate of pathological International Society of Urological Pathology (ISUP) ≥ 2 with the increase of PSIM. At the multivariate logistic regression analysis adjusted for age, prostate specific antigen (PSA), PSA density, prostate volume and PSIM, the latter was found the sole independent prognostic variable influencing probability of adverse pathology.

Increased Mortality Among Men Diagnosed With Impaired Fertility: Analysis of US Claims Data.

OBJECTIVE: To determine whether male infertility or impaired spermatogenesis is associated with mortality. METHODS: The Optum de-identified Clinformatics Data Mart database was queried from 2003 to 2017. Infertile men were compared to subjects undergoing semen analysis (ie, infertility testing). Infertile men with oligozoospermia or azoospermia were included. Mortality was determined by data linkage to the Social Security Administration Death Master File. Results were adjusted for age, smoking, obesity, year of evaluation, and health care visits as well as for most prevalent comorbidities. We separately examined men with prevalent or incident cardiovascular disease and cancer diagnoses to determine associations with mortality. RESULTS: A total of 134,796 infertile men and 242,282 controls were followed for a mean of 3.6 and 3.1 years respectively. Overall, infertile men had a higher risk of death (Hazard Ratio [HR]= 1.42, 95% CI: 1.27-1.60) The diagnosis of azoospermia was associated with a significantly increased risk of death (HR= 2.01, 95% CI: 1.60-2.53) with a higher trend among men with oligospermia (HR: 1.17, 95% CI: 0.92-1.49) compared to controls. Subanalysis was done excluding prevalent cardiovascular and malignant disease (alone and combined) showing similar hazard ratios. CONCLUSION: Male infertility is associated with a higher risk of mortality especially among azoospermic men. Prevalent disease (which is known to be higher among infertile men) did not explain the higher risk of death among infertile men. The implications for treatment and surveillance of infertile men require further study.

Contemporary Assessment of Survival Rates in Stage I Testicular Seminoma: A Population-Based Comparison Between Surveillance and Active Treatment After Orchiectomy.

BACKGROUND: We tested contemporary surveillance and active treatment (AT) that included chemotherapy (CHT) and radiotherapy (RT) rates for stage I testicular seminoma patients, as well as cancer-specific mortality (CSM) and other-cause mortality (OCM) rates. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (1988-2015) we identified 11,206 stage I testicular seminoma patients. Surveillance versus CHT versus RT use rates were investigated using estimated annual percentage change (EAPC) analyses. After propensity score (PS) matching, cumulative incidence plots and multivariable competing risks regression models (MCRRMs) tested for CSM and OCM. RESULTS: Of all 11,206 patients, 4434 (40%), 918 (8%), and 5854 (52%), respectively, underwent surveillance, CHT, or RT after initial orchiectomy. Surveillance (EAPC: 7.5%; P < .001) and CHT (EAPC: 13.5%; P < .001) rates increased over time, whereas RT rates decreased (EAPC: -3.8%; P < .001). After PS matching, in MCRRMs surveillance was an independent predictor of CSM, relative to AT (hazard ratio [HR], 2.59; P = .04). Conversely, surveillance versus AT did not affect OCM (HR, 1.52; P = .051). All other analyses that focused on CSM and OCM, namely surveillance versus RT, surveillance versus CHT, and RT versus CHT resulted in nonsignificant differences (all P > .5). CONCLUSION: Surveillance and CHT use in stage I testicular seminoma rates increased, whereas RT rate decreased over time. A protective effect of AT defined as either RT or CHT was identified on CSM, relative to surveillance. This protective effect was not described for OCM. No differences in survival were recorded, when individual management strategies (surveillance vs. RT vs. CHT) were compared with each other.

Low PI-RADS assessment category excludes extraprostatic extension (≥pT3a) of prostate cancer: a histology-validated study including 301 operated patients.

OBJECTIVES: To evaluate whether low PI-RADS v2 assessment categories are effective at excluding extraprostatic extension (EPE) of prostate cancer (≥pT3a PCa). METHODS: The local institutional ethics committee approved this retrospective analysis of 301 consecutive PCa patients. Patients were classified as low- or intermediate/high-risk based on clinical parameters and underwent pre-surgical multiparametric magnetic resonance imaging. A PI-RADS v2 assessment category and ESUR EPE score were assigned for each lesion by two readers working in consensus. Histopathologic analysis of the whole-mount radical prostatectomy specimen was the reference standard. Univariate and multivariate analyses were performed to evaluate the association of PI-RADS v2 assessment category with final histology ≥pT3a PCa. RESULTS: For a PI-RADS v2 assessment category threshold of 3, the overall performance for ruling out (sensitivity, negative predictive value, negative likelihood ratio) ≥pT3a PCa was 99%/98%/0.04 and was similar in both the low-risk (96%/97%/0.12; N = 137) and the intermediate/high-risk groups (100%/100%/0.0; N = 164). In univariate analysis, all clinical and tumor characteristics except age were significantly associated with ≥pT3a PCa. In multivariate analysis, PI-RADS v2 assessment categories ≤ 3 had a protective effect relative to categories 4 and 5. The inclusion of ESUR EPE score improved the AUC of ≥pT3a PCa prediction (from 0.73 to 0.86, p = 0.04 in the overall cohort). The impact of PI-RADS v2 assessment category is reflected in a nomogram derived on the basis of our cohort. CONCLUSIONS: In our cohort, low PI-RADS v2 assessment categories of 3 or less confidently ruled out the presence of ≥pT3a PCa irrespective of clinical risk group. KEY POINTS: • Our analysis of 301 mp-MRI and RARP specimens showed that the addition of PI-RADS v2 assessment categories to clinical parameters improves the exclusion of ≥pT3a (extraprostatic) prostate cancer. • PI-RADS v2 assessment categories of 1 to 3 are useful for excluding ≥pT3a prostate cancer with a NPV of 98%; such patients can be considered as candidates for less invasive approaches. • The ability to exclude ≥pT3a prostate cancer may improve confidence in choosing nerve-sparing surgery or in avoiding pelvic nodal dissections, and similarly for patients undergoing radiotherapy, in adopting short-course adjuvant hormonal therapy or foregoing prophylactic nodal irradiation.

Cell-cycle Progression-score Might Improve the Current Risk Assessment in Newly Diagnosed Prostate Cancer Patients.

OBJECTIVE: To assess whether cell-cycle progression (CCP)-score (Prolaris) can improve the current risk assessment in newly diagnosed prostate cancer (PCa) patients. CCP-score is a well-validated prognostic assay predictive of PCa death, biochemical recurrence, and progression. METHODS: We evaluated CCP-score at biopsy in 52 patients newly diagnosed with PCa who underwent radical prostatectomy. CCP-score was calculated as average RNA expression of 31 CCP genes, normalized to 15 housekeeping genes. The predictive ability of CCP-score was assessed in univariate and multivariate analyses, and compared to that of Ki-67 levels and traditional clinical variables including prostate-specific antigen, Gleason score, stage, and percentage of positive cores at biopsy. RESULTS: In spite of an overall good accuracy in attributing the correct risk class, 7 high-risk and 13 intermediate-risk patients were misclassified by the Prolaris test. On analysis of variance, mean CCP-score significantly differed across different risk classes based on pathologic results (-1.2 in low risk, -0.444 in intermediate risk, 0.208 in high risk). CCP-score was a significant predictor of high-risk PCa both on univariate and multivariate analyses, after adjusting for clinical variables. Combining CCP-score and the European Association of Urology clinical risk assessment improved the accuracy of risk attribution by around 10%, up to 87.8%. CCP-score was a significant predictor of biochemical recurrence, but only on univariate analysis. CONCLUSION: The CCP-score might provide important new information to risk assessment of newly diagnosed PCa in addition to traditional clinical variables. A correct risk attribution is essential to tailor the best treatment for each patient.

Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

BACKGROUND/AIM: Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. MATERIALS AND METHODS: The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. RESULTS: We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). CONCLUSION: PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS).