Briganti, Alberto

114 Background: High-risk prostate cancer (HRPC) is a challenging disease and the role of surgery is often considered in the context of a multimodal approach. The indication for adjuvant therapy after surgery for HRPC patients who have specimen-confined disease (R0, pN0, <pT3b) is still difficult. The current study aims to analyze postoperative pathological features which help to predict CSS in specimen-confined HRPC and thus may aid in the decision to administer adjuvant EBRT or ADT. Methods: From a multi-institutional retrospective cohort of 5876 HRPC patients treated by radical prostatectomy and pelvic lymph node dissection, 1391 patients with specimen-confined disease were selected. Following surgery, adjuvant EBRT and/or ADT were delivered according to institutional protocols. Patients were subdivided into four groups according to pT stage (pT≥3 and pT<3) and final Gleason score (GS≥8 and GS<8). Kaplan-Meier plots with log-rank tests and a Cox proportional hazards model were applied to study CSS. All significance levels were set at 0.05. MedCalc was used for all statistical analyses. Results: Median age was 65 years (43-84). Of all patients, 346 (24.9%) had GS≥8 and 794 (57.1%) had pT≥3 at definitive histopathology. Patients were classified into COMBO groups: C1 (478; 34.4%; GS<8,pT<3), C2 (567; 40.8%; GS<8, pT≥3), C3 (119; 8.6%; GS≥8, pT<3), C4 (227; 16.3%; GS≥8, pT≥3). Adjuvant EBRT and ADT, respectively, were delivered in C1 2%/2%, C2 15%/22%, C3 3%/10%, C4 18%/25%. Kaplan Meier plots demonstrated statistically different 10-yr CSS between groups: C1 97.4%, C2 95.2%, C3 89.9% and C4 84.4% (p<0.0001). COMBO groups were also compared using a Cox model and results are shown in the Table. Conclusions: COMBO groups demonstrated to be able to subdivide specimen-confined HRPC into 4 demarcated groups with significantly different CSS. This subdivision could be considered an easy-to-use tool which can help for counseling patients for adjuvant treatment strategies. [Table: see text]

84 Background: In elderly patients, Charlson score among other features, might allow clinicians to limit the use of aggressive adjuvant treatment strategies or even primary surgical treatment to those who might not achieve benefit during their lifetime. Methods: Retrospective analysis, 7,650 case multicenter high-risk prostate cancer (Pca) radical prostatectomy database selecting >= 70 years old cases. We predicted death from all causes (DAC) and cancer related death (CRD) including all clinical and pathological data. Multivariable analysis were performed to identify independent predictors of DAC and CRD with binary logistic regression, using STATA® software, version 13.1. Results: 2,106 patients from 14 high-volume centers were included. Mean age was 72.8 years (SD 2.46). 206 (9.78%) patients were classified as ASA 3-4 and 497 (23.6%) as CS >=1. Mean PSA was 21.7 ng/ml (SD 50.5). At final histopathology, 800 (38%) had pT3b-T4 disease, GS was 8-10 in 589 (28%), LNI was found in 518 (24.6%) and 822 (39%) PSM. Adjuvant RT, ADT and RT+ADT were administered in 359 (17%), 391 (18.6%) and 437 (20.7%), respectively. Mean follow up was 5.18 years (DS 4.47). BCR occur in 649 (30.8%) and CF in 150 (7.1%) of which distant in 59 (2.8%). Total deaths accounted 341 (16.2%) and CRD for 100 (4.7%) cases. Conclusions: Multicenter data confirms that elderly patients survival harboring high risk prostate cancer will benefit from radical treatment if they are Charlson score 1 or less. [Table: see text] [Table: see text]

Objectives To identify which patients with macroscopic bladder‐infiltrating T4 prostate cancer ( PC a) might have favourable outcomes when treated with radical cystectomy ( RC ). Materials and Methods We evaluated 62 patients with cT 4cN0–1 cM0 PC a treated with RC and pelvic lymph node dissection between 1972 and 2011. In addition to descriptive statistics, the Kaplan–Meier method and log‐rank tests were used to depict survival rates. Univariate and multivariate Cox regression analysis tested the association between predictors and progression‐free, PC a‐specific and overall survival. Results Of the 62 patients, 19 (30.6%) did not have clinical progression during follow‐up, two (3.2%) had local recurrence, and 32 (51.6%) had haematogenous and nine (14.5%) combined pelvic and distant metastasis. Forty patients (64.5%) died, 34 (54.8%) from PC a and six (9.7%) from other causes. The median (range) survival time of the 19 patients who were metastasis‐free at last follow‐up was 86 (1–314) months, 8/19 patients had a follow‐up of >5 years, and five patients survived metastasis‐free for >15 years. Patients without seminal vesicle invasion ( SVI ) had the best outcomes, with an estimated 10‐year PC a‐specific survival of 75% compared with 24% for patients with SVI . Conclusion For cT 4 PC a RC can be an appropriate treatment for local control and part of a multimodality‐treatment approach. Although recurrences are probable, these do not necessarily translate into cancer‐specific death. Men without SVI had a 75% 10‐year PC a‐specific survival. Although outcomes for patients with SVI are not as favourable, there can be good local control; however, these patients are at higher risk of progression and may need more aggressive systemic treatment.

BACKGROUNDA new prostate cancer (PCa) grading system (namely, Gleason score‐GS‐ ≤6 vs. 3 + 4 vs. 4 + 3 vs. 8 vs. ≥9) was recently proposed and assessed on biochemical recurrence (BCR) showing improved predictive abilities compared to the commonly used three‐tier system (GS ≤6 vs. 7 vs. ≥8). We assessed the predictive ability of the five‐tier grade group (GG) system on harder clinical endpoint, namely clinical recurrence (CR).METHODSBetween 2005 and 2014, 9,728 clinically localized PCa patients were treated with radical prostatectomy (RP) at two tertiary referral centers. Kaplan–Meier curves, multivariable Cox regression analyses, and concordance index (C‐index) were used to assess CR after treatment according to four Gleason grade classifications at biopsy and RP: Group 1: ≤6 versus 7 versus ≥8; Group 2: ≤6 versus 3 + 4 vs. 4 + 3 versus ≥8; Group 3: ≤6 versus 7 versus 8 versus ≥9; Group 4: ≤6 versus 3 + 4 versus 4 + 3 versus 8 versus ≥9. Same analyses were repeated in patients who had BCR (n = 1,624). Decision curve analyses were performed to evaluate and compare the net benefit associated with the use of the four Gleason grade classifications.RESULTSOverall, 443 (4.6%) patients had CR. The hazard ratio of the GS 3 + 4, 4 + 3, 8, and ≥9 relative to GS ≤6 were 3.63, 5.93, 11.44, 18.08 and 4.93, 9.99, 15.31 and 25.12 in the pre‐ and post‐treatment models, respectively. The C‐index of the five‐tier GG system was slightly higher relative to the other 3 Gleason grade classifications both in the pre‐ (range: 0.001–0.006) and post‐treatment models (range: 0–0.008). Similar findings were observed when we focused our analyses in patients with BCR after RP. The use of the five‐tier GG system did not result into higher net‐benefit relative to the other three Gleason grade classifications.CONCLUSIONSThe difference in accuracy between the five‐tier GG system and the other Gleason grade classifications, using CR as an endpoint, is clinically negligible. Current evidence suggests that the five‐tier GG system represents a simplified user‐friendly scheme available for patient counseling rather than a new histopathological diagnostic system that improves the prediction of CR. Prostate 77:263–273, 2017. © 2016 Wiley Periodicals, Inc.

Objective To investigate the long‐term utility of adjuvant therapy after radical prostatectomy ( RP ) for prostate cancer with seminal vesicle invasion ( SVI ; pT 3b), as the published data are conflicting. Patients and Methods Patients with SVI during RP and pelvic lymph node dissection at two major referral centres from 1986 to 2014 were included. Kaplan–Meier analyses and multivariable Cox regressions were used to determine if adjuvant radiotherapy ( aRT ) and adjuvant hormonal therapy ( aHT ) were predictors of biochemical recurrence ( BCR ), cancer‐specific mortality ( CSM ) and overall mortality ( OM ). Subset analyses were performed for pN 0 patients and pN + patients. Results Overall, 3 279 patients with prostate cancer and SVI were included with a median follow‐up of 148 months. Considering the whole SVI population, 1 387 (42%) received no adjuvant therapy, 1 179 (36%) received aHT , 461 (14.1%) received aRT , while 252 (7.7%) received both aHT and aRT . The 10‐year BCR , CSM , and OM rates were 64%, 14%, and 27%, respectively. In the overall population, aRT and aHT were predictors of BCR , CSM and OM (all P < 0.04). When only pT 3bN0 patients were considered, aHT was a significant multivariate predictor of BCR [hazard ratio ( HR ) 0.50, P < 0.001), CSM ( HR 0.62, P = 0.01) and OM ( HR 0.75, P = 0.004). Conversely, aRT was not associated with survival outcomes (all P > 0.05). When only the subgroup pT 3bN+ was considered, the use of aRT was related to an improvement in CSM ( HR 0.65, P = 0.03) and OM (HR 0.78, P = 0.03). Conclusions aHT + aRT seems to be effective in pT 3b patients. However, when stratified according to the presence of nodal metastases, aHT remains effective only in the node‐negative subgroup, while aRT remains effective only in the node‐positive subgroup. Further data including prospective trials are warranted to study the utility of adjuvant therapies in this setting.

Objectives To determine if a re‐transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1‐high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS). Patients and methods In a large retrospective multicentre cohort of 2451 patients with T1‐HG/G3 initially treated with bacille Calmette–Guérin, 935 (38%) had a re‐TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re‐TUR), group 2 (no muscle, re‐TUR), group 3 (muscle, no re‐TUR) and group 4 (muscle, re‐TUR). Clinical outcomes were compared across the four groups. Results Re‐TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re‐TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re‐TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints. Conclusions Our retrospective analysis suggests that re‐TUR may not be necessary in patients with T1‐HG/G3, if muscle is present in the specimen of the primary TUR.

Objective To assess the impact of primary or progressive status on recurrence‐free survival ( RFS ), cancer‐specific mortality ( CSM ) and overall mortality ( OM ) after radical cystectomy ( RC ) for muscle‐ invasive bladder cancer ( MIBC ). Patients and Methods A total of 768 consecutive patients underwent RC as treatment for MIBC at our institution between 2000 and 2012. Primary MIBC was defined as no previous history of bladder cancer and progressive was defined as recorded previous treated non‐ MIBC ( NMIBC ) that had progressed to MIBC . The median follow‐up was 85 (60–109) months. Univariate and multivariate Cox regression models were used to compare RFS , CSM and OM between these two cohorts. Results In all, 475 (61.8%) patients had primary and 293 (38.2%) patients had progressive MIBC . There were no differences between the two groups in terms of demographics, pathological and peri‐operative complications (all P > 0.1). The 10‐year RFS , CSM and OM rates for primary vs progressive status were 43 vs 36% ( P = 0.01), 43 vs 37% ( P = 0.01), and 35 vs 28% ( P = 0.03), respectively. On multivariable Cox regression analyses, progressive status remained significantly associated with a higher rate of recurrence (hazard ratio [ HR ] 1.47, 95% confidence interval [ CI ] 1.12–1.79; P = 0.03), CSM ( HR 1.42, 95% CI 1.07–1.89; P = 0.01) and OM ( HR 1.42, 95% CI 1.13–1.65; P = 0.02). Conclusions Among patients treated with RC for MIBC , progressive status was associated with a higher CSM , OM and recurrence rate after RC . The present study thus provides an impetus to improve risk sub‐stratification when bladder cancer is still at the NMIBC stage, be it through new biomarkers or improved imaging, as a subset of patients with NMIBC are likely to benefit from early RC .

Purpose The role of adjuvant radiotherapy (aRT) in treating patients with pN1 prostate cancer is controversial. We tested the hypothesis that the impact of aRT on cancer-specific mortality (CSM) in these individuals is related to tumor characteristics. Methods We evaluated 1,107 patients with pN1 prostate cancer treated with radical prostatectomy and anatomically extended pelvic lymph node dissection between 1988 and 2010 at two tertiary care centers. All patients received adjuvant hormonal therapy with or without aRT. Regression tree analysis stratified patients into risk groups on the basis of their tumor characteristics and the corresponding CSM rate. Cox regression analysis tested the relationship between aRT and CSM rate, as well as overall mortality (OM) rate in each risk group separately. Results Overall, 35% of patients received aRT. At multivariable analysis, aRT was associated with more favorable CSM rate (hazard ratio [HR], 0.37; P < .001). However, when patients were stratified into risk groups, only two groups of men benefited from aRT: (1) patients with positive lymph node (PLN) count ≤ 2, Gleason score 7 to 10, pT3b/pT4 stage, or positive surgical margins (HR, 0.30; P = .002); and (2) patients with PLN count of 3 to 4 (HR, 0.21; P = .02), regardless of other tumor characteristics. These results were confirmed when OM was examined as an end point. Conclusion The beneficial impact of aRT on survival in patients with pN1 prostate cancer is highly influenced by tumor characteristics. Men with low-volume nodal disease (≤ two PLNs) in the presence of intermediate- to high-grade, non–specimen-confined disease and those with intermediate-volume nodal disease (three to four PLNs) represent the ideal candidates for aRT after surgery.

Objective To determine the association between peri‐operative blood transfusion ( PBT ) and oncological outcomes in a large multi‐institutional cohort of patients undergoing radical cystectomy ( RC ) for urothelial carcinoma of the bladder ( UCB ). Patients and Methods We conducted a retrospective analysis of 2895 patients treated with RC for UCB . Univariable and multivariable C ox regression models were used to analyse the effect of PBT administration on disease recurrence, cancer‐specific mortality, and any‐cause mortality. Results Patients' median (interquartile range [ IQR ]) age was 67 (60, 73) years and the median ( IQR ) follow‐up was 36.1 (15, 84) months. Patients who received PBT were more likely to have advanced disease ( P < 0.001), high grade tumours ( P = 0.047) and nodal metastasis ( P = 0.004). PBT was associated with a higher risk of disease recurrence ( P = 0.003), cancer‐specific mortality ( P = 0.017), and any‐cause mortality ( P = 0.010) in univariable, but not multivariable, analyses ( P > 0.05). In multivariable analyses, pathological tumour stage, pathological nodal stage, soft tissue surgical margin, lymphovascular invasion and administration of adjuvant chemotherapy were independent predictors of disease recurrence, cancer‐specific mortality and any‐cause mortality (all P values <0.002). Conclusions Patients with UCB who underwent RC and received PBT had a greater risk of disease recurrence, cancer‐specific mortality and any‐cause mortality in univariable, but not multivariable, analysis. Although the greater need for PBT with more advanced disease is probably caused by a number of factors, including surgical and cancer‐related factors, the present analysis showed that the disease characteristics rather than need for PBT led to worse outcomes.