Detectable Prostate-specific antigen value between 0.01 and 0.1 ng/ml following robotic-assisted radical prostatectomy (RARP): does it correlate with future biochemical recurrence?

PURPOSE: The aim of the study is to evaluate the impact of having a nadir and persistently detectable ultrasensitive prostate-specific antigen (uPSA) between 0.01 and 0.1 ng/ml post-robot-assisted radical prostatectomy (RARP), on future biochemical recurrence (BCR). METHODS: We conducted a retrospective analysis of a prospectively maintained cohort of 1359 men who underwent RARP, between 2006 and 2019. Patients were followed with uPSA at 1, 3, 6, 9, 12, 18, 24, 30, 36 months and annually thereafter. We included patients with PSA nadir values between 0.01 and 0.1 ng/ml within 6 months of surgery and with at least 2 follow-up measurements within the same range. We divided patients based on their BCR status and analyzed uPSA changes. Multivariable Cox-regression models (CRMs) were used to analyze variables predicting BCR-free survival (BCR-FS). RESULTS: We identified 167 (12.3%) patients for analyses, with a mean follow-up time of 60.2 ± 31.4 months. In our cohort, 5-year BCR-FS rate was 86%. Overall, 32 (19.1%) patients had BCR, with a mean time to BCR of 43.7 ± 24.3 months. BCR-free patients had stable mean uPSA values ≤ 0.033 ng/ml, while patients who developed BCR showed a slowly rising trend over time, with a significant difference between groups starting at 9 months (p < 0.02). In multivariable CRMs, a rising uPSA starting at 9 months was an independent predictor of BCR (HR: 2.7; 95% CI 1.6-3.82; p = 0.013). CONCLUSION: In the present cohort, our results demonstrated that a considerable number of men have detectable uPSA values ranging between 0.01 and 0.1 ng/ml post-RARP. They can still be followed regularly to avoid patients' anxiety and salvage radiotherapy. Close follow-up is still required.

Functional and perioperative outcomes in elderly men after robotic-assisted radical prostatectomy for prostate cancer.

PURPOSE: We aimed to compare postoperative functional outcomes following robotic-assisted radical prostatectomy (RARP) in elderly men with localized prostate cancer. METHODS: A retrospective review of a prospectively maintained database of men who underwent RARP between January 2007 and November 2018 was performed. Patients over 65 years of age were selected (N = 302) and then stratified by age group: 66-69 years old (N = 214) and ≥ 70 years old (N = 88). Full continence was defined as strict 0-pad per day usage. Preoperative potency included those with a Sexual Health Inventory for Men score ≥ 17. Preoperative and postoperative functional outcomes were assessed. Kaplan-Meier analysis was used to estimate time to recovery of continence in both groups. RESULTS: Both groups had comparable preoperative parameters. Continence rates at 1, 3, 6, 9, 12, 18 and 24 months in the 66-69-year-old group were 6%, 34%, 61%, 70%, 74%, 80% and 87%, respectively. Comparatively in the ≥ 70-year-old group, continence rates were significantly lower at all time points (3%, 22%, 50%, 56%, 66%, 69% and 75%, respectively). Men in the 66-69-year-old group were significantly more likely to be continent after RARP when compared to patients 70 years of age and above [(Hazards ratio (HR) 0.73; 95%confidence interval 0.54-0.97, (p = 0.035)]. CONCLUSION: Our results suggest that RARP is feasible in elderly patients. Nevertheless, elderly patients in the ≥ 70-year-old group had significantly inferior postoperative continence rates compared to patients aged 66-69 years. Such information is valuable when counselling men during preoperative RARP planning to ensure that they have realistic postoperative expectations.

Oncological and functional outcomes of a large Canadian robotic-assisted radical prostatectomy database with 10 years of surgical experience.

INTRODUCTION: Robotic-assisted radical prostatectomy (RARP) has grown to be the predominant global surgical approach to treat localized prostate cancer. However, there is still limited access to robotic technology and little data from Canadian cohorts. Herein, we report on our oncological and functional outcomes after 10 years of surgical experience. MATERIALS AND METHODS: Prospective data from 1,034 RARP cases performed by two high-volume experienced surgeons at two academic centers were collected from October 2006 to June 2017. Preoperative characteristics, surgical, oncological and functional outcomes were assessed up to 72 months postoperative. RESULTS: D'Amico risk distribution was 26.1%, 59.8% and 14.1% for low, intermediate and high risk prostate cancer. Median (interquartile range) operative time, blood loss and hospital stay were 170 minutes (145-200), 200 mL (150-300) and 1day (1-1), respectively and 1.4% received blood transfusion. Intraoperative complications occurred in 3.8%. Postoperatively, 32 (3.1%) and 138 (13.3%) men harbored major (Clavien III-IV) and minor complications (Clavien I-II), respectively. Among the 630 men (64.2%) with pT2 and 349 men (35.6%) with pT3 disease, stage-specific positive surgical margin rates were 15.7% and 39.0%, respectively. Urinary continence rates at 6, 12 and 72 months were 72.7%, 83.5% and 84.9%, respectively. In men without preoperative erectile dysfunction, potency was observed in 45.6%, 59.4% and 69.5% at 6, 12 and 72 months, respectively. Biochemical recurrence occurred in 105 patients (10.2%). CONCLUSION: Mid-term oncological outcomes in two large Canadian centers demonstrate comparable results to non-Canadian centers of excellence. RARP appears to be safe with acceptable surgical, oncological and functional outcomes in a publicly funded single-payer healthcare system.

Accuracy of Clarius, Handheld Wireless Point-of-Care Ultrasound, in Evaluating Prostate Morphology and Volume Compared to Radical Prostatectomy Specimen Weight: Is There a Difference between Transabdominal vs Transrectal Approach?

Background: Prostate size estimation is a valuable clinical measure widely utilized in urology. This study evaluated the accuracy of preoperative transabdominal ultrasound (TAUS) compared to radical prostatectomy specimens and transrectal ultrasound (TRUS) in estimating prostate volume and identifying presence of median lobe, across different size groups, using the standard ellipsoid formula. The effect of median lobe on accuracy was also assessed. Materials and Methods: Ninety-eight men undergoing robot-assisted radical prostatectomy were enrolled in this study. Preoperative evaluation of prostate volume was done using measurements obtained from TAUS using the Clarius C3 handheld wireless point-of-care ultrasound (POCUS) and from TRUS Clarius EC7. Participants were grouped based on prostate size (<30, 30-60, and >60 g). Mean absolute percentage of error was used to evaluate accuracy. Mean percentage of error determined if there was an overestimation or underestimation. Correlation between each TAUS size group, true prostate weight and TRUS was assessed. Results: Irrespective of body mass index, TAUS accurately identified median lobe in all men. No statistically significant difference was found between specimen weight and TAUS prostate size for the >60 g group. Among this same group, a strong correlation was noted between specimen weight and TAUS prostate size (r = 0.911, p < 0.001). There was also a strong correlation between TAUS and TRUS measurements for this group (r = 0.950, p < 0.001). Presence of median lobe did not have an impact on measurement accuracy. Conclusions: Bedside handheld wireless POCUS provides rapid, inexpensive, noninvasive, and clinically accurate TAUS prostate assessments for larger prostates. Such features as identifying median lobes and measuring prostate volumes are valuable tools, whereas patient counseling on lower urinary tract symptoms, elevated prostate-specific antigen, and benign prostate hyperplasia are surgical options.

Unmarried men have worse oncologic outcomes after radical cystectomy for nonmetastatic urothelial bladder cancer.

BACKGROUND: Unmarried status is an established risk factor for worse cancer control outcomes and survival in various malignancies. We tested the effect of marital status on the rate of nonorgan confined disease as well as on cancer-specific mortality (CSM) in patients who underwent radical cystectomy for nonmetastatic urothelial bladder cancer (UCUB). METHODS: Within the Surveillance, Epidemiology and End Results database (2007-2015), we identified 11,167 patients (8,639 men and 2,528 women) who underwent radical cystectomy for nonmetastatic UCUB. Temporal trend analyses, logistic regression models, cumulative incidence plots, competing-risks regression models and landmark analyses were used. RESULTS: Overall, 2,454 men (28.4%) and 1,363 women (53.9%) were unmarried. Unmarried men had a higher rate of nonorgan-confined disease at radical cystectomy (OR: 1.24, CI 1.10-1.33; P < 0.001). Moreover, in men, unmarried status was an independent predictor of higher CSM (HR: 1.24, CI 1.12-1.37) In women, unmarried status neither predicted nonorgan-confined disease at radical cystectomy (OR: 1.07, CI 0.91-1.26; P = 0.37) nor was it associated with CSM (HR: 1.13, CI 0.88-1.31; P = 0.14). In 6-month landmark analyses, unmarried status remained an independent predictor of higher CSM in men (HR: 1.20, CI 1.08-1.33). CONCLUSIONS: Unmarried men have more advanced tumor stage at radical cystectomy and worse CSM compared to married men. Interestingly, marital status did not affect oncologic outcomes in women. These data suggest a gender-specific effect of marital status in UCUB.

External beam radiation therapy improves survival in high- and intermediate-risk non-metastatic octogenarian prostate cancer patients.

PURPOSE: There is no contemporary proof of cancer-control benefits in octogenarian clinically localized prostate cancer (PCa) patients with life expectancy (LE) < 10 years. Therefore, cancer-specific mortality (CSM) rates after external beam radiation therapy (EBRT) vs. no local treatment (NLT) were tested in octogenarian PCa patients with LE < 10 years. METHODS: Within the surveillance, epidemiology, and end results database (2004-2015), we identified 22,361 octogenarian clinically localized PCa patients who either received EBRT or NLT. Temporal trends, cumulative incidence plots and multivariable competing-risks regression analyses (MCR) were used after propensity score matching. Sensitivity analyses were performed according to D'Amico risk groups and LE > 5 years. RESULTS: Of all, 7325 (32.8%) received EBRT vs. 15,036 (67.2%) received NLT. Rates of EBRT significantly increased over time (25.0-42.4%). Overall, 10-year CSM rates were 10.6% vs. 17.0% and 10-year other-cause mortality rates were 50.3% vs. 58.1%, in EBRT vs. NLT patients (both p < 0.001). In MCR focusing on the overall cohort, EBRT represented an independent predictor of lower CSM (hazard ratio: 0.5). In sensitivity analyses, hazard ratios of 0.5 (p < 0.001), 0.5 (p < 0.001) and 0.8 (p = 0.5) were, respectively, recorded in D'Amico high-, intermediate- and low-risk patients. In sensitivity analyses addressing patients with LE > 5 years virtually the same results were recorded. CONCLUSIONS: In octogenarian patients with LE < 10 years, EBRT seems to be associated with lower CSM in D'Amico high-risk, as well as in D'Amico intermediate-risk patients relative to their NLT counterparts. Based on these observations, greater consideration for EBRT may be given in octogenarian patients.

Complication rates, failure to rescue and in-hospital mortality after cytoreductive nephrectomy in the older patients.

OBJECTIVES: Historical data showed worse perioperative outcomes after cytoreductive nephrectomy (CN) in older patients. Additionally, the CARMENA trial questioned the survival benefit of cytoreductive CN. We reassessed complication, failure to rescue (FTR) and mortality rates after CN in a contemporary cohort of older patients with metastatic renal cell carcinoma (mRCC). MATERIALS AND METHODS: From National Inpatient Sample (NIS) database (2008-2015), mRCC patients treated with CN were abstracted. Univariable and multivariable logistic regression models tested for the relationship between age (≤55 vs. 56-70 vs ≥71 years), Charlson Comorbidity Index (CCI) and modified Frailty Index (mFI) categories and complications, FTR and in-hospital mortality. All models were clustered, weighted and adjusted for all available patient and hospital characteristics. RESULTS: Of 3644 mRCC patients treated with CN, 924 (25.4%) were ≥ 71 years old, 435 (11.9%) had CCI ≥ 2 and 749 (20.6%) were frail. In multivariable logistic regression models, age ≥ 71 (odds ratio [OR] 1.4, p < .001), CCI ≥ 2 (OR 1.88, p < .001) and frail status (OR 1.91, p < .001) were independent predictors of overall complications. Age ≥ 71 was also an independent predictor of FTR (OR 2.27, p = .04), but not of in-hospital mortality. Both CCI and mFI were not significantly associated with either FTR or in-hospital mortality. CONCLUSION: Older patients with mRCC are more likely to experience higher rates of overall complications, FTR and in-hospital mortality following CN. These results highlight the importance of rigorous selection criteria for older surgical candidates. Moreover, timely recognition and rapid response to complications are particularly critical in this population.

Contemporary Cytoreductive Nephrectomy Provides Survival Benefit in Clear-cell Metastatic Renal Cell Carcinoma.

INTRODUCTION: A recent randomized trial questioned the role of cytoreductive nephrectomy in clear-cell metastatic renal cell carcinoma (ccmRCC). We reassessed the effect of cytoreductive nephrectomy on survival in a contemporary population-based ccmRCC cohort. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2010-2015), we focused on patients with ccmRCC. The primary endpoint consisted of overall mortality. Univariable and multivariable Cox regression models were applied in the overall cohort and in patients who underwent targeted therapy. Sensitivity analyses included 1:1 propensity score matching, 3- and 6-month landmark analyses, incremental survival benefit analyses, and metastases number and location-based stratifications. RESULTS: Of 4062 patients with ccmRCC, 2241 (55.1%) received targeted therapy; cytoreductive nephrectomy was performed in 2226 (54.8%) patients and 1168 (52.1%) patients in the overall and targeted therapy cohorts, respectively. Cytoreductive nephrectomy was associated with lower overall mortality in the overall cohort (median survival, 30 vs. 9 months; hazard ratio [HR], 0.43; P < .001), as well as in the targeted therapy cohort (median survival, 28 vs. 12 months; HR, 0.49; P < .001). In sensitivity analyses, cytoreductive nephrectomy was associated with lower overall mortality after 1:1 propensity score-matching (HR, 0.49; P < .001), in 3- and 6-month landmark analyses (HR, 0.49; P < .001 and HR, 0.51; P < .001, respectively), in metastases number and location-based stratifications, except for exclusive liver metastases, as well as in all incremental benefit analyses. CONCLUSION: Cytoreductive nephrectomy is associated with better survival in patients with ccmRCC, including those exposed to targeted therapy, after adjustment for multiple potential confounders.

Unmarried status is a barrier for access to treatment in patients with metastatic renal cell carcinoma.

PURPOSE: We tested the effect of marital status on cytoreductive nephrectomy, metastasectomy, and systemic therapy rates, as well as on cancer-specific mortality (CSM) in patients with metastatic clear cell renal carcinoma (mccRCC). METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), we identified 6975 patients (4806 men and 2169 women) with metastatic clear cell renal carcinoma. Temporal trend analyses, logistic regression models, cumulative incidence plots, and competing-risk regression models were used. RESULTS: Overall, 1450 men and 1018 women were unmarried (30.2% and 47.0%, respectively). In men, unmarried status was an independent predictor of lower cytoreductive nephrectomy rate (OR: 0.54), lower metastasectomy rate (OR: 0.70), and lower systemic therapy rate (OR: 0.70). Conversely, in women, unmarried status was an independent predictor of lower cytoreductive nephrectomy rate (OR: 0.63) and of lower systemic therapy rate (OR: 0.80), but not of lower metastasectomy rate (OR: 0.83; p = 0.12). In multivariable competing-risk regression analyses, unmarried status was an independent predictor of higher CSM in men (HR: 1.15), but not in women (HR 0.97, p = 0.6). CONCLUSIONS: Unmarried men are at higher risk of not benefiting of cytoreductive nephrectomy, metastasectomy, or systemic therapy than their married counterparts. Unmarried women are at higher risk of not benefiting of cytoreductive nephrectomy or systemic therapy. These gender-related differences cumulate in higher CSM in unmarried men, but not in unmarried women.

External validation of the novel International Society of Urological Pathology (ISUP) Gleason grading groups in a large contemporary Canadian cohort.

INTRODUCTION: We sought to test the discriminatory ability of the 2014 International Society of Urological Pathology (ISUP) Gleason grading groups (GGG) for predicting biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP) in a large, contemporary, Canadian cohort. METHODS: A total of 621 patients who underwent RARP in two major Canadian centres were identified in a prospectively maintained Canadian database between 2006 and 2016. Followup endpoint was BCR. Log-rank test, univariable, and multivariable Cox regression analyses were used. RESULTS: Mean followup was 27.9 months. All five ISUP GGG independently predicted BCR. Statistically significant differences in BCR rates were found between GGG 2 and GGG 3 strata (p<0.001). No statistically significant differences in BCR rates were found between GGG 4 and GGG 5 strata (p=0.3). Relative to GGG 1, the GGG 2, GGG 3, GGG 4, and GGG 5 yielded a 1.10-, 3.44-, 4.18-, and 4.74-fold hazard ratio (HR) increment in BCR, respectively. CONCLUSIONS: This population-based Canadian cohort study confirms the added discriminatory property of the novel ISUP grading, specifically for GGG 2 and GGG 3 strata. No difference, however, was observed between GGG 4 and GGG 5, likely due to the lower number of patients in these groups. As such, after external validation, the 2014 ISUP GGG appears to retain clinical prognostic significance in a Canadian population.

Functional and oncological outcomes of salvage external beam radiotherapy following robot-assisted radical prostatectomy in a Canadian cohort.

INTRODUCTION: We sought to determine the impact of salvage radio-therapy (SRT) on oncological and functional outcomes of patients with prostate cancer after biochemical recurrence (BCR) following robot-assisted radical prostatectomy (RARP). METHODS: Data of 70 patients with prostate cancer treated with SRT after developing BCR were retrospectively analyzed from a prospectively collected RARP database of 740 men. Oncological (prostate-specific antigen [PSA]) and functional (pads/day, International Prostate Symptom Score [IPSS], and Sexual Health Inventory for Men [SHIM]) outcomes were reported at six, 12, and 24 months after RT and adjusted for pre-SRT status. RESULTS: Men who underwent SRT had a mean age, PSA, and time from radical prostatectomy (RP) to RT of 61.8 years (60.1-63.6), 0.5 ng/ml (0.2-0.8), and 458 days (307-747), respectively. Freedom from biochemical failure (FFBF) post-SRT, defined as a PSA nadir <0.2 ng/mL, was observed in 89%, 93%, and 81%, at six, 12, and 24 months, respectively. Undetectable PSA was observed in 14%, 35%, and 40% at the same time points, respectively. There was no significant difference in urinary continence post-SRT (p=0.56). Rate of strict continence (0 pads/day) was 71% at 24 months compared to 78% pre-SRT. Mean IPSS at six, 12, and 24 months was 3.4, 3.6, and 3.6, respectively compared to pre-RT score of 3.3 (p=0.61). The mean SHIM score pre-SRT was comparable at all time points following treatment (p=0.86). CONCLUSIONS: In this unique Canadian experience, it appears that early SRT is highly effective for the treatment of BCR following RARP with little impact on urinary continence and potency outcomes.