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Background: This study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa). Material and Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004–2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer vs. secondary PCa diagnoses. Results: We identified 24,848 secondary PCa patients (skin, n = 3,871; rectal, n = 798; colon, n = 3,665; lymphoma, n = 2,583; leukemia, n = 1,102; pancreatic, n = 118; stomach, n = 361; esophagus, n = 219; liver, n = 160; lung, n = 1,328) vs. 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa. Conclusion: Patients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis.
Purpose: To test the value of preoperative and postoperative cystatin C (CysC) as a predictor on kidney function after partial (PN) or radical nephrectomy (RN) in renal cell carcinoma (RCC) patients with normal preoperative renal function.
Methods: From 01/2011 to 12/2014, 195 consecutive RCC patients with a preoperative estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73m2 underwent surgical RCC treatment with either PN or RN. Logistic and linear regression models tested for the effect of CysC as a predictor of new-onset chronic kidney disease in follow-up (eGFR < 60 ml/min/1.73m2). Moreover, postoperative CysC and creatinine values were compared for kidney function estimation.
Results: Of 195 patients, 129 (66.2%) underwent PN. In postoperative and in follow-up setting (median 14 months, IQR 10–20), rates of eGFR < 60 ml/min/1.73m2 were 55.9 and 30.2%. In multivariable logistic regression models, preoperative CysC [odds ratio (OR): 18.3] and RN (OR: 13.5) were independent predictors for a reduced eGFR < 60 ml/min/1.73m2 in follow-up (both p < 0.01), while creatinine was not. In multivariable linear regression models, a difference of the preoperative CysC level of 0.1 mg/dl estimated an eGFR decline in follow-up of about 5.8 ml/min/1.73m2. Finally, we observed a plateau of postoperative creatinine values in the range of 1.2–1.3 mg/dl, when graphically depicted vs. postoperative CysC values (‘creatinine blind area’).
Conclusion: Preoperative CysC predicts renal function impairment following RCC surgery. Furthermore, CysC might be superior to creatinine for renal function monitoring in the early postoperative setting.
Background: To test the effect of urological primary cancers (bladder, kidney, testis, upper tract, penile, urethral) on overall mortality (OM) after secondary prostate cancer (PCa). Methods: Within the Surveillance, Epidemiology and End Results (SEER) database, patients with urological primary cancers and concomitant secondary PCa (diagnosed 2004-2016) were identified and were matched in 1:4 fashion with primary PCa controls. OM was compared between secondary and primary PCa patients and stratified according to primary urological cancer type, as well as to time interval between primary urological cancer versus secondary PCa diagnoses. Results: We identified 5,987 patients with primary urological and secondary PCa (bladder, n = 3,287; kidney, n = 2,127; testis, n = 391; upper tract, n = 125; penile, n = 47; urethral, n = 10) versus 531,732 primary PCa patients. Except for small proportions of Gleason grade group and age at diagnosis, PCa characteristics between secondary and primary PCa were comparable. Conversely, proportions of secondary PCa patients which received radical prostatectomy were smaller (29.0 vs. 33.5%), while no local treatment rates were higher (34.2 vs. 26.3%). After 1:4 matching, secondary PCa patients exhibited worse OM than primary PCa patients, except for primary testis cancer. Here, no OM differences were recorded. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis. Conclusions: After detailed matching for PCa characteristics, secondary PCa patients exhibit worse survival, except for testis cancer patients. The survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary urological cancer diagnosis.
Purpose: To test the effect of anatomic variants of the prostatic apex overlapping the membranous urethra (Lee type classification), as well as median urethral sphincter length (USL) in preoperative multiparametric magnetic resonance imaging (mpMRI) on the very early continence in open (ORP) and robotic-assisted radical prostatectomy (RARP) patients. Methods: In 128 consecutive patients (01/2018–12/2019), USL and the prostatic apex classified according to Lee types A–D in mpMRI prior to ORP or RARP were retrospectively analyzed. Uni- and multivariable logistic regression models were used to identify anatomic characteristics for very early continence rates, defined as urine loss of ≤ 1 g in the PAD-test. Results: Of 128 patients with mpMRI prior to surgery, 76 (59.4%) underwent RARP vs. 52 (40.6%) ORP. In total, median USL was 15, 15 and 10 mm in the sagittal, coronal and axial dimensions. After stratification according to very early continence in the PAD-test (≤ 1 g vs. > 1 g), continent patients had significantly more frequently Lee type D (71.4 vs. 54.4%) and C (14.3 vs. 7.6%, p = 0.03). In multivariable logistic regression models, the sagittal median USL (odds ratio [OR] 1.03) and Lee type C (OR: 7.0) and D (OR: 4.9) were independent predictors for achieving very early continence in the PAD-test. Conclusion: Patients’ individual anatomical characteristics in mpMRI prior to radical prostatectomy can be used to predict very early continence. Lee type C and D suggest being the most favorable anatomical characteristics. Moreover, longer sagittal median USL in mpMRI seems to improve very early continence rates.
Background: Number of positive prostate biopsy cores represents a key determinant between high versus very high-risk prostate cancer (PCa). We performed a critical appraisal of the association between the number of positive prostate biopsy cores and CSM in high versus very high-risk PCa. Methods: Within Surveillance, Epidemiology, and End Results database (2010–2016), 13,836 high versus 20,359 very high-risk PCa patients were identified. Discrimination according to 11 different positive prostate biopsy core cut-offs (≥2–≥12) were tested in Kaplan–Meier, cumulative incidence, and multivariable Cox and competing risks regression models. Results: Among 11 tested positive prostate biopsy core cut-offs, more than or equal to 8 (high-risk vs. very high-risk: n = 18,986 vs. n = 15,209, median prostate-specific antigen [PSA]: 10.6 vs. 16.8 ng/ml, <.001) yielded optimal discrimination and was closely followed by the established more than or equal to 5 cut-off (high-risk vs. very high-risk: n = 13,836 vs. n = 20,359, median PSA: 16.5 vs. 11.1 ng/ml, p < .001). Stratification according to more than or equal to 8 positive prostate biopsy cores resulted in CSM rates of 4.1 versus 14.2% (delta: 10.1%, multivariable hazard ratio: 2.2, p < .001) and stratification according to more than or equal to 5 positive prostate biopsy cores with CSM rates of 3.7 versus 11.9% (delta: 8.2%, multivariable hazard ratio: 2.0, p < .001) in respectively high versus very high-risk PCa. Conclusions: The more than or equal to 8 positive prostate biopsy cores cutoff yielded optimal results. It was very closely followed by more than or equal to 5 positive prostate biopsy cores. In consequence, virtually the same endorsement may be made for either cutoff. However, more than or equal to 5 positive prostate biopsy cores cutoff, based on its existing wide implementation, might represent the optimal choice.
Objectives: To test the effect of race/ethnicity on cancer-specific mortality after radical prostatectomy or external beam radiotherapy in localized prostate cancer patients. Methods: In the Surveillance, Epidemiology and End Results database 2004–2016, we identified intermediate-risk and high-risk white (n = 151 632), Asian (n = 11 189), Hispanic/Latino (n = 20 077) and African American (n = 32 550) localized prostate cancer patients, treated with external beam radiotherapy or radical prostatectomy. Race/ethnicity-stratified cancer-specific mortality analyses relied on competing risks regression, after propensity score matching for patient and cancer characteristics. Results: Compared with white patients, Asian intermediate- and high-risk external beam radiotherapy patients showed lower cancer-specific mortality (hazard ratio 0.58 and 0.70, respectively, both P ≤ 0.02). Additionally, Asian high-risk radical prostatectomy patients also showed lower cancer-specific mortality than white patients (hazard ratio 0.72, P = 0.04), but not Asian intermediate-risk radical prostatectomy patients (P = 0.08). Conversely, compared with white patients, African American intermediate-risk radical prostatectomy patients showed higher cancer-specific mortality (hazard ratio 1.36, P = 0.01), but not African American high-risk radical prostatectomy or intermediate- and high-risk external beam radiotherapy patients (all P ≥ 0.2). Finally, compared with white people, no cancer-specific mortality differences were recorded for Hispanic/Latino patients after external beam radiotherapy or radical prostatectomy, in both risk levels (P ≥ 0.2). Conclusions: Relative to white patients, an important cancer-specific mortality advantage applies to intermediate-risk and high-risk Asian prostate cancer patients treated with external beam radiotherapy, and to high-risk Asian patients treated with radical prostatectomy. These observations should be considered in pretreatment risk stratification and decision-making.
Background: To test for differences in cancer-specific mortality (CSM) rates between radical prostatectomy (RP) vs external beam radiotherapy (EBRT) in National Comprehensive Cancer Network (NCCN) high-risk African American patients, as well as Johns Hopkins University (JHU) high-risk and very high-risk patients.
Materials and methods: Within the Surveillance, Epidemiology, and End Results database (2010–2016), we identified 4165 NCCN high-risk patients, of whom 1944 (46.7%) and 2221 (53.3%) patients qualified for JHU high-risk or very high-risk definitions. Of all 4165 patients, 1390 (33.5%) were treated with RP versus 2775 (66.6%) with EBRT. Cumulative incidence plots and competing risks regression models addressed CSM before and after 1:1 propensity score matching between RP and EBRT NCCN high-risk patients. Subsequently, analyses were repeated separately in JHU high-risk and very high-risk subgroups. Finally, all analyses were repeated after landmark analyses were applied.
Results: In the NCCN high-risk cohort, 5-year CSM rates for RP versus EBRT were 2.4 versus 5.2%, yielding a multivariable hazard ratio of 0.50 (95% confidence interval [CI] 0.30–0.84, p = 0.009) favoring RP. In JHU very high-risk patients 5-year CSM rates for RP versus EBRT were 3.7 versus 8.4%, respectively, yielding a multivariable hazard ratio of 0.51 (95% CI: 0.28–0.95, p = 0.03) favoring RP. Conversely, in JHU high-risk patients, no significant CSM difference was recorded between RP vs EBRT (5-year CSM rates: 1.3 vs 1.3%; multivariable hazard ratio: 0.55, 95% CI: 0.16–1.90, p = 0.3). Observations were confirmed in propensity score-matched and landmark analyses adjusted cohorts.
Conclusions: In JHU very high-risk African American patients, RP may hold a CSM advantage over EBRT, but not in JHU high-risk African American patients.
Background: The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treatment alternatives.
Methods: We performed a systematic review and network meta-analysis focusing on OS and AE according to the most recent apalutamide, enzalutamide, and darolutamide reports. We systematically examined and compared apalutamide vs. enzalutamide vs. darolutamide efficacy and toxicity, relative to ADT according to PRISMA. We relied on PubMed search for most recent reports addressing prospective randomized trials with proven predefined OS benefit, relative to ADT: SPARTAN, PROSPER, and ARAMIS. OS represented the primary outcome and AEs represented secondary outcomes.
Results: Overall, data originated from 4117 observations made within the three trials that were analyzed. Regarding OS benefit relative to ADT, darolutamide ranked first, followed by enzalutamide and apalutamide, in that order. In the subgroup of PSA-doubling time (PSA-DT) ≤ 6 months patients, enzalutamide ranked first, followed by darolutamide and apalutamide in that order. Conversely, in the subgroup of PSA-DT 6–10 months patients, darolutamide ranked first, followed by apalutamide and enzalutamide, in that order. Regarding grade 3+ AEs, darolutamide was most favorable, followed by enzalutamide and apalutamide, in that order.
Conclusion: The current network meta-analysis suggests the highest OS efficacy and lowest grade 3+ toxicity for darolutamide. However, in the PSA-DT ≤ 6 months subgroup, the highest efficacy was recorded for enzalutamide. It is noteworthy that study design, study population, and follow-up duration represent some of the potentially critical differences that distinguish between the three studies and remained statistically unaccounted for using the network meta-analysis methodology. Those differences should be strongly considered in the interpretation of the current and any network meta-analyses.
Background: To examine overall survival rates within a large cohort of German prostate cancer (PCa) patients and to compare these with life-expectancy (LE) predictions derived from German life tables. We hypothesized that the advantage of good general health in radical prostatectomy (RP) patients combined with favorable cancer outcomes might lead to even higher overall survival rates over 10 years compared to the LE of a general population.
Methods: A total of 6483 patients were treated with RP between 1992 and 2007 at the Martini-Klinik Prostate Cancer Center. Preoperative risk classification was performed according to D'Amico. Postoperative risk classification was performed according to the Cancer of the Prostate Risk Assessment score (CAPRA-S). A simulated cohort was created that resembled the exact age distribution of the RP population using Monte Carlo simulation which was based on data derived from official male German life tables (1992–2017). Markov chain was used to represent natural age progression of the simulated cohort. Kaplan–Meier plots were created to display the differences between 10-year observed overall survival (OS) and the simulated, predicted LE.
Results: For D'Amico low risk and intermediate risk, 10-year OS was 12.0% and 9.2% above predicted LE in the simulated cohort, respectively. For D'Amico high risk, OS was virtually the same as predicted LE (0.8% difference in favor of RP treated patients). For CAPRA-S low and intermediate risk, OS was 11.8% and 9.7% above predicted LE. For CAPRA-S high risk, OS was virtually the same as predicted LE (0.3% difference in favor of the simulated cohort).
Conclusions: Low- and intermediate risk PCa patients treated with RP can expect a very favorable overall survival, that even exceeds LE predictions. High risk patients' overall survival perfectly aligns with LE predictions.
Purpose: We assessed contemporary incidence rates and trends of primary urethral cancer.
Methods: We identified urethral cancer patients within Surveillance, Epidemiology and End Results registry (SEER, 2004–2016). Age-standardized incidence rates per 1,000,000 (ASR) were calculated. Log linear regression analyses were used to compute average annual percent change (AAPC).
Results: From 2004 to 2016, 1907 patients with urethral cancer were diagnosed (ASR 1.69; AAPC: -0.98%, p = 0.3). ASR rates were higher in males than in females (2.70 vs. 0.55), respectively and did not change over the time (both p = 0.3). Highest incidence rates were recorded in respectively ≥75 (0.77), 55–74 (0.71) and ≤54 (0.19) years of age categories, in that order. African Americans exhibited highest incidence rate (3.33) followed by Caucasians (1.72), other race groups (1.57) and Hispanics (1.57), in that order. A significant decrease occurred over time in Hispanics, but not in other race groups. In African Americans, male and female sex-stratified incidence rates were higher than in any other race group. Urothelial histological subtype exhibited highest incidence rate (0.92), followed by squamous cell carcinoma (0.41), adenocarcinoma (0.29) and other histologies (0.20). In stage stratified analyses, T1N0M0 stage exhibited highest incidence rate. However, it decreased over time (−3.00%, p = 0.02) in favor of T1-4N1-2M0 stage (+ 2.11%, p = 0.02).
Conclusion: Urethral cancer is rare. Its incidence rates are highest in males, elderly patients, African Americans and in urothelial histological subtype. Most urethral cancer cases are T1N0M0, but over time, the incidence of T1N0M0 decreased in favor of T1-4N1-2M0.