Fossati, Nicola

AbstractObjectiveTo evaluate the relationship between pre‐operative PSA value, 68Ga‐prostate‐specific‐membrane‐antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa).Patients and methodsThe study included 164 patients diagnosed with ≤2 pelvic lymph‐node recurrence(s) of PCa documented on 68Ga‐PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high‐volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (<0.5 ng/ml), low (0.5–0.99 ng/ml), moderate (1–1.5 ng/ml) and high (>1.5 ng/ml). Clinical recurrence (CR)‐free survival after sLND was calculated using multivariable analyses and plotted over pre‐operative PSA value.ResultsMedian [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre‐operative PSA value, with highest rates for patients with pre‐operative PSA > 1.5 ng/ml (pelvic‐only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre‐operative PSA was associated with PSA response (p < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non‐linear relationship between PSA level at sLND and the 12‐month CR‐free survival (p < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml.ConclusionsIn case of PET‐detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short‐term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68Ga‐PSMA PET in biochemical recurrent PCa.

Objective To assess the relationship between the volume of the index lesion (IL) measured at multiparametric magnetic resonance imaging (mpMRI; MRIvol) and at radical prostatectomy (RPvol), stratifying it according to Prostate Imaging‐Reporting and Data System (PI‐RADS) score. Patients and Methods We identified 332 men with a positive mpMRI (single lesion with PI‐RADS ≥3) who underwent systematic plus targeted biopsy and subsequent RP at two tertiary referral centres between 2013 and 2018. All mpMRIs were reviewed by experienced radiologists using PI‐RADS scores. The study outcome was to assess the relationship between MRIvol (based on planimetry from MRI sequence best showing tumour) and RPvol (based on tumour involved area of each RP pathology slice). To achieve this endpoint, we performed a multivariable linear regression analysis (LRA) to predict RPvol using PI‐RADS, prostate‐specific antigen level, prostate volume, age, digital rectal examination, Gleason score at MRI‐targeted biopsy, biopsy history and time from mpMRI to RP as covariates. Non‐parametric locally estimated scatterplot smoothing (LOESS) function was used to graphically explore the relationship between MRIvol and RPvol, stratifying for PI‐RADS score. Results Overall, 24%, 49% and 27% of men had visible PI‐RADS 3, 4 and 5 lesions at mpMRI. The median (interquartile range [IQR]) MRIvol and RPvol were 0.67 (0.29–1.76) mL and 1.39 (0.58–4.23) mL. At LRA, MRIvol was significantly correlated with a RPvol underestimation (slope: 2.4, 95% confidence interval [CI] 0.1–46.3). The non‐parametric LOESS analysis showed a non‐linear relationship between MRIvol and RPvol. Significant underestimation was reported across all volumes with the highest differences between MRIvol and RPvol in the low volume range (<2 mL), where RPvol almost doubled MRIvol. A similar effect was observed across all PI‐RADS scores subgroups. Conclusions In the present study, mpMRI significantly underestimated the exact volume of the IL, especially for small visible lesions, regardless of PI‐RADS score. This should be considered when planning tailored focal therapy approaches often delivered to men with smaller prostatic lesions.

241 Background: Androgen deprivation represents the standard treatment for PCA with osseous metastases. We explored the role of cRP in the largest cohort of contemporary patients with mPCA treated in 4 tertiary referral centres. Methods: A total of 114 patients with mPCA, lymph node, osseous or visceral metastases underwent cRP. Surgery related complications (Clavien-Dindo classification) and functional outcome were analysed. Oncologic outcome parameters such as cancer specific & overall survival as well as biochemical and clinical-free survival were evaluated using descriptive statistical analysis. Results: Mean patient age was 61 (42-69) years. Mean and median follow-up was 39.7 months (7-75) and 47 months (28-96), resp. 93 (81.6%) and 21 (18.4%) patients had low volume and high volume mets, resp.,. 80(70.2%) pts underwent neoadjuvant ADT with LHRH analogues. Surgical approach was open retropubic RP in 104 (92%) pts and 2 (1.8%), 10 (8.8%) and 101 (89.4%) pts underwent no, limited or extended pelvic LAD, resp. Adjuvant therapy was delivered in 99 (86.8%) pts. Pathohistology revealed significant vital PCA in 100% of cases: n = 16 (14.0%) exhibited pT4a, n = 21 (18.4%) had pT2 and the remainder had pT3a/b PCA. Positive lymph nodes or positive surgical margins were identified in 61.6% and 36.8%, resp.. 110 (96.5%) are alive and 66.7% are relapse-free. 74 (64.9%) pts did not experience any surgery related complications; 15 (13.1%) pts experienced Clavien Dindo grade IIIb/IV complications and underwent reintervention. Low versus high volume (32.2% vs 50%, p = 0.03), PSA at cRP < 1ng/ml vs PSA > 4 ng/ml, (18.9% vs 45.6%, p = 0.02) were associated with relapse. Low vs high volume disease (7.1% vs 32.1%), PSA < 4ng/ml vs PSA > 4 ng/ml (6.1% vs 47.8%) and neoadjuvant vs no neoadjuvant therapy (8.75% vs 24.2%) were associated with Clavien-Dindo IIIB complications (p < 0.05). Conclusions: cRP is feasible in men with mPCA independent on the extent of disease with a low rate of significant complications and good functional outcome. About two thirds of the patients remain relapse-free after a median follow-up of close to 4 years. cRP might be an individualized treatment option in the multimodality management of mPCA.

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.

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.