Location-Based Oncological Outcomes of Sentinel Node Dissection in Radical Prostatectomy.

PURPOSE: To assess the oncological outcomes of sentinel-node dissection during radical prostatectomy according to nodal location in comparison to extended pelvic lymph node dissection. MATERIALS AND METHODS: Prospectively collected data of clinically node negative patients that underwent prostatectomy and extended lymph node dissection with or without sentinel-node from 2013 to January 2023 was retrospectively analyzed. The primary endpoint was to assess oncological outcomes on the whole population. Kaplan-Meier curves were used to depict biochemical and clinical recurrence free survival. Multivariable Cox regression models assessed the impact of nodal location on SPECT on oncological outcomes. Adjustment for case mix included: pathological T stage, ISUP grade group, initial PSA, nodal burden, age at surgery and surgical margin status. Secondarily, a propensity score match was performed according to age at surgery, PSA, biopsy ISUP, clinical T stage and Briganti risk of nodal invasion. Survival and regression analyses were than performed also in the matched population. RESULTS: 55.8% patients had at least one sentinel node outside of lymph node dissection template at SPECT/CT. Log-rank test showed comparable 36-months biochemical (P = .3) and clinical recurrence-free survival (P = .6) among patients with sentinel-node inside template, outside template or ePLND alone. At Cox regression, sentinel-node location outside template was associated with lower hazard of metastases (HR 0.62; P = .04) in the overall cohort, while in the matched cohort benefits were observed only for biochemical recurrence (HR 0.57; P = .001). CONCLUSIONS: Wider nodal resection boundaries outside "classic" template, driven by sentinel node procedure, have a positive impact on oncological outcomes in selected patient.

Use of Soft Penile Prosthesis in Grafting Surgery for Peyronie's Disease and Mild Erectile Dysfunction: Still an Option?

BACKGROUND: Plaque incision and grafting (PEG) is a primary surgical therapy for severe penile curvature in Peyronie's disease (PD); However, it can increase the risk of erectile dysfunction (ED), particularly in patients with pre-operative mild ED. Soft penile prosthesis (SPP) implantation is a viable treatment option in such cases. This study aims to compare the outcomes of PEG-only approach to PEG plus SPP implantation. METHODS: Between 2010 and 2019, 32 patients with PD and mild ED (5-item version of the International Index of Erectile Function scores: 17-21) underwent PEG surgery. Two groups were defined based on the surgery type: PEG-only and PEG plus SPP. The long-term outcomes included correction of penile bending, erection quality, intercourse ability, penile length and sensitivity. The overall satisfaction and impact of surgery on sexual activity and quality of life were also assessed. RESULTS: Of the 32 patients, 13 (40.6%) underwent PEG-only surgery, whereas 19 (59.4%) underwent PEG plus SPP. No significant differences were noted between the groups regarding pre-operative characteristics (all p > 0.1) or intra- and post-operative complication rates (all p > 0.2). The median patch area was larger in the PEG-only group (28 cm2 vs. 16.2 cm2; p = 0.001), whereas patients in the PEG plus SPP group were more likely to receive a single patch implant (100% vs. 53.8%; p < 0.001). The penile length increased in 18 patients (61.6%), with significant differences between the two groups (30% vs. 81.2%; p = 0.03). Overall, 14 patients (53.8%) reported greater satisfaction with their sexual life post-operatively, with comparable rates between the groups (p = 0.2). No significant differences were found in the post-operative 5-item version of the International Index of Erectile Function scores or severe post-operative ED (all p > 0.5). CONCLUSIONS: SPP placement during corporoplasty in patients with mild ED is safe and feasible, and it may be a suitable option for patients uncertain about inflatable prosthesis placement. The use of SPP resulted in longer penile lengths and necessitated smaller grafts. However, further data are required to understand the long-term clinical implications of this approach.

Immunohistochemistry analysis of PSMA expression at prostatic biopsy in high-risk prostate cancer: potential implications for PSMA-PET patient selection.

Introduction: Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed by normal prostatic tissue. Therefore, molecular imaging targeting PSMA (PSMA-PET) has gained particular interest and diffusion for PCa staging and restaging. Several factors may affect PSMA-PET results, and many tools have been proposed to improve patient selection. Furthermore, PSMA expression is not homogeneous among different tissues and within the prostate itself. The aims of this study were to evaluate immunohistochemistry (IHC) features of prostate biopsy samples and to assess their correlation with whole-mount specimens and PSMA-PET parameters. Methods: We included consecutive high-risk PCa patients who underwent PSMA-PET for staging proposal at our institution from January 2022 to December 2022. The PET parameters selected were SUVmax, total volume (TV), and total lesion activity (TL). Each patient underwent multiparametric MRI (mpMRI) and fusion-targeted prostate biopsy prior to surgery. IHC analyses were performed on the index lesion cores. IHC visual score (VS) (1, 2, 3) and visual pattern (VP) (membranous, cytoplasmic, and combined) and the percentage of PSMA-negative tumor areas (PSMA%neg) within biopsy cores were evaluated. Results: Forty-three patients who underwent robotic radical prostatectomy after PSMA-PET were available for analyses. Concordance between VS and VP at biopsy and final pathology showed a Cohen's kappa coefficient of 0.39 and 0.38, respectively. Patients with PSMA%neg <20% had a higher concordance in VS and VP (Cohen's kappa 0.49 and 0.4, respectively). No difference emerged in terms of median PSMA-TV (p = 0.3) and PSMA-TL (p = 0.9) according to VS at biopsy, while median SUVmax was higher in patients with VS 3 (p = 0.04). Higher SUVmax was associated with membranous and combined VP expression (p = 0.008). No difference emerged between patients with PSMA%neg <20% or PSMA%neg >20% on biopsy cores in terms of SUVmax, PSMA-TL, and PSMA-TV (p = 0.5, p = 0.5, and p = 0.9 respectively). Conclusions: We found a correlation between IHC VS and VP on targeted biopsy cores and SUVmax at PSMA-PET. However, the correlation between the IHC parameters of biopsy cores and final pathology was not as high as expected. Nevertheless, the presence of PSMA%neg <20% seems to have a better concordance in terms of visual score.

Evaluation of an institutional series of low-grade oncocytic tumor (LOT) of the kidney and review of the mutational landscape of LOT.

The 2022 WHO classification of urinary and male genital tumors introduced several novel kidney entities exhibiting eosinophilic/oncocytic features with specific mutational backgrounds. Thus, molecular techniques, such as next-generation sequencing (NGS), became more commonly used for their evaluation. We studied 12 low-grade oncocytic tumors (LOT) of the kidney (from 11 patients), identified in a cohort of 210 eosinophilic/oncocytic renal tumors, diagnosed in our institution between October 2019 and May 2023, which represented 5.7% (12/210) of all eosinophilic/oncocytic renal tumors during this period. We reviewed their clinicopathologic, histologic, and immunohistochemical features, as well as their mutational profiles. We also reviewed the literature on NGS-derived data of LOT, by selecting papers in which LOT diagnosis was rendered according to the criteria proposed initially. Median age was 65 years (mean: 63.5; range 43-79) and median tumor size was 2.0 cm (mean: 2.2; range: 0.9-3.1). All tumors were positive for PAX8, CK7, and GATA3, and negative or focally positive for CD117/KIT. We found the following gene mutations: MTOR ((6/11), 54.5%)), TSC1 ((2/11), 18.2%)), and 1 had both NOTCH1 and NOTCH4 ((1/11), 9.1%)). Wild-type status was found in 2/11 (18.2%) patients and one tumor was not analyzable. A review of 8 previous studies that included 79 LOTs revealed frequent mutations in the genes that regulate the mammalian target of rapamycin (mTOR) pathway: MTOR (32/79 (40.5%)), TSC1 (21/79 (26.6%)), and TSC2 (9/79 (11.4%)). Other mutated genes included PIK3CA, NF2, and PTEN, not typically known to affect the mTOR pathway, but potentially acting as upstream and downstream effectors. Our study shows that LOT is increasingly diagnosed in routine practice when applying the appropriate diagnostic criteria. We also confirm that the mTOR pathway is strongly implicated in the pathogenesis of this tumor mainly through MTOR, TCS1, and TSC2 mutations, but other genes could also be involved in the pathway activation, especially in LOTs without "canonical" mutations.

Is radiotherapy after radical prostatectomy associated with higher other-cause mortality?

PURPOSE: The aim of this study was to reveal the association between the other-cause mortality (OCM) and post-radical prostatectomy (RP) salvage radiotherapy (sRT) in men with prostate cancer (PCa). METHODS: A retrospective study was carried out with patients who had PCa and underwent RP ± sRT in a high-volume cancer center between 2005 and February 2019. Data from 1955 patients were subjected to a 1:1 matching for age, initial PSA, pathological (p)T/N stages, and ISUP score, which yielding 439 RP + RT (group 1) vs 439 RP-only cases (group 2), without any residual difference. Primary and secondary endpoints of the study were OCM and cancer-specific mortality (CSM). Kaplan-Meier, log-rank, and cox regression tests were used for purpose of the study. RESULTS: The median follow-up time after RP was 5.3 years (interquartile range: 4.0-7.3). After matching, of all deaths that occurred during the study period, 16 in group 1 and 35 in group 2 were attributed to other causes (p = 0.006). 5-year OCM rate of patients who received sRT (1.2%) was significantly lower compared to patients that underwent RP-only (4.4%, p < 0.001). 19 versus 16 patients died of PCa, respectively (p = 0.61). There was no CSM risk difference between groups (p = 0.29). Older patients had an increased risk of OCM (hazard ratio [HR]:1.10 [95%CI 1.05-1.17], p < 0.001) and post-RP RT was associated with lower OCM (HR: 0.28 [95%CI 0.15-0.51], p < 0.001) in multivariable model. pT/N stages and ISUP score were strongly associated with CSM, but not with OCM. CONCLUSION: OCM was not higher in patients who had sRT with or without ADT. Excess OCM in favor of RP-only patients may be cautiously explained with higher-performance status/life expectancy of patients who selected for RT after RP in our cohort.

Multiparametric magnetic resonance imaging for the differential diagnosis between granulomatous prostatitis and prostate cancer: a literature review to an intriguing diagnostic challenge.

Multiparametric magnetic resonance imaging (mpMRI) is currently the most effective diagnostic tool for detecting prostate cancer (PCa) and evaluating adenocarcinoma-mimicking lesions of the prostate gland, among which granulomatous prostatitis (GP) represents the most interesting diagnostic challenge. GP consists of a heterogeneous group of chronic inflammatory lesions that can be differentiated into four types: idiopathic, infective, iatrogenic, and associated with systemic granulomatous disease. The incidence of GP is growing due to the increase in endourological surgical interventions and the adoption of intravesical instillation of Bacillus Calmette-Guerin in patients with non-muscle invasive bladder cancer; therefore, the difficulty lies in identifying specific features of GP on mpMRI to avoid the use of transrectal prostate biopsy as much as possible.

PSMA-PET Guided Treatment in Prostate Cancer Patients with Oligorecurrent Progression after Previous Salvage Treatment.

BACKGROUND: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients. METHODS: we performed a retrospective analysis of 113 recurrent PCa after previous radical prostatectomy and salvage therapies with oligorecurrent disease at PSMA-PET (≤3 lesions in N1/M1a-b) in three high-volume European centres. Patients underwent second-line salvage treatments: MDT targeted to PSMA (including surgery and/or radiotherapy), and the conventional approach (observation or Androgen Deprivation Therapy [ADT]). Patients were stratified according to treatments (MDT vs. conventional approach). Patients who underwent MDT were stratified according to stage in PSMA-PET (N1 vs. M1a-b). The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were Metastases-free survival (MFS) and Castration Resistant PCa free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS. Multivariable Cox regression models identified predictors of progression and metastatic disease. RESULTS: Overall, 91 (80%) and 22 (20%) patients were treated with MDT and the conventional approach, respectively. The median follow-up after PSMA-PET was 31 months. Patients who underwent MDT had a similar PFS compared to the conventional approach (p = 0.3). Individuals referred to MDT had significantly higher MFS and CRPC-FS compared to those who were treated with the conventional approach (73.5% and 94.7% vs. 30.5% and 79.5%; all p ≤ 0.001). In patients undergoing MDT, no significant differences were found for PFS and MFS according to N1 vs. M1a-b disease, while CRPC-FS estimates were significantly higher in patients with N1 vs. M1a-b (100% vs. 86.1%; p = 0.02). At multivariable analyses, age (HR = 0.96) and ADT during second line salvage treatment (HR = 0.5) were independent predictors of PFS; MDT (HR 0.27) was the only independent predictor of MFS (all p ≤ 0.04) Conclusion: Patients who underwent second-line PSMA-guided MDT experienced higher MFS and CRPC-FS compared to men who received conventional management.

Histology and PSMA Expression on Immunohistochemistry in High-Risk Prostate Cancer Patients: Comparison with 68Ga-PSMA PET/CT Features in Primary Staging.

PSMA-PET/CT is a suitable replacement for conventional imaging in the primary staging of PCa. The aim of this retrospective study was to assess the correlation between parameters discovered by PSMA PET/CT in primary staging and either prostate histopathology (pT) findings or PSMA-IHC expression in a cohort of biopsy-proven high-risk PCa candidates for surgery. Clinical information (age, iPSA-value, and grading group) and PSMA-PET/CT parameters (SUVmax, PSMA tumor volume [PSMA-TV], and total lesion [PSMA-TL]) were compared with pT (including histologic pattern, Gleason grade, and lymphovascular invasion [LVI]) and PSMA-IHC features, including visual quantification (VS) with a four-tiered score (0 = negative, 1+ = weak, 2+ = moderate, 3+ = strong), growth pattern (infiltrative vs expansive), and visual pattern (cytoplasmic vs membranous). In total, 44 patients were enrolled, with a median age of 67 (IQR 57-77); the median iPSA was 9.4 ng/dL (IQR 12.5-6.0). One patient (3%) was grading group (GG) 3, 27/44 (61%) were GG4, and 16/44 (36%) were GG5. PSMA-PET/CT detection rate for the presence of primary prostate cancer was 100%. Fused/poorly formed Gleason grade 4 features were predominant (22/44-50%); a cribriform pattern was present in 18/44 (41%) and acinar in 4/44 (9%). We found that lower PSMA-TVs were mostly related to acinar, while higher PSMA-TVs correlated with a higher probability to have a cribriform pattern (p-value 0.04). LVI was present in 21/44(48%) patients. We found that higher PSMA-TV and PSMA-TL are predictive of LVI p-value 0.002 and p-value 0.01, respectively. There was no correlation between PET-parameters and perineural invasion (PNI), probably because this was present in almost all the patients. Moreover, patients with high PSMA-TL values displayed the highest PSMA-IHC expression (VS3+) with a membranous pattern. In conclusion, PSMA-TV and PSMA-TL are predictors of a cribriform pattern and LVI. These conditions are mostly related to higher aggressiveness and worse outcomes.

Transverse prostate maximum sectional area can predict clinically significant prostate cancer in PI-RADS 3 lesions at multiparametric magnetic resonance imaging.

Background: To evaluate multiparametric magnetic resonance imaging (mpMRI) parameters, such as TransPA (transverse prostate maximum sectional area), TransCGA (transverse central gland sectional area), TransPZA (transverse peripheral zone sectional area), and TransPAI (TransPZA/TransCGA ratio) in predicting prostate cancer (PCa) in prostate imaging reporting and data system (PI-RADS) 3 lesions. Methods: Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), the area under the receiver operating characteristic curve (AUC), and the best cut-off, were calculated. Univariate and multivariate analyses were carried out to evaluate the capability to predict PCa. Results: Out of 120 PI-RADS 3 lesions, 54 (45.0%) were PCa with 34 (28.3%) csPCas. Median TransPA, TransCGA, TransPZA and TransPAI were 15.4cm2, 9.1cm2, 5.5cm2 and 0.57, respectively. At multivariate analysis, location in the transition zone (OR=7.92, 95% CI: 2.70-23.29, P<0.001) and TransPA (OR=0.83, 95% CI: 0.76-0.92, P<0.001) were independent predictors of PCa. The TransPA (OR=0.90, 95% CI: 0.082-0.99, P=0.022) was an independent predictor of csPCa. The best cut-off of TransPA for csPCa was 18 (Sensitivity 88.2%, Specificity 37.2%, PPV 35.7%, NPV 88.9%). The discrimination (AUC) of the multivariate model was 0.627 (95% CI: 0.519-0.734, P<0.031). Conclusions: In PI-RADS 3 lesions, the TransPA could be useful in selecting patients requiring biopsy.

Multicenter External Validation of a Nomogram for Predicting Positive Prostate-specific Membrane Antigen/Positron Emission Tomography Scan in Patients with Prostate Cancer Recurrence.

BACKGROUND: A nomogram has recently been developed to predict 68Ga-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (PSMA-PET) results in recurrent prostate cancer (PCa) patients. OBJECTIVE: To perform external validation of the original nomogram in a multicentric setting. DESIGN, SETTING, AND PARTICIPANTS: A total of 1639 patients who underwent PSMA-PET for prostate-specific antigen (PSA) relapse after radical therapy were retrospectively included from six high-volume PET centers. The external cohort was stratified according to clinical setting categories: group 1: first-time biochemical recurrence (n = 774); group 2: PSA relapse after salvage therapy (n = 499); group-3: biochemical persistence after radical prostatectomy (n = 210); and group-4: advanced-stage PCa before second-line systemic therapies (n = 124). INTERVENTION: PSMA-PET in recurrent PCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSMA-PET detection rate was assessed in the overall population and in each subgroup. A multivariable logistic regression model was produced to evaluate the predictors of a positive scan. The performance characteristics of the model were assessed by quantifying the predictive accuracy (PA) according to model calibration. The Youden's index was used to find the best nomogram's cutoff. Decision curve analysis (DCA) was implemented to quantify the nomogram's clinical net benefit. RESULTS AND LIMITATIONS: In the external cohort, the overall detection rate was 53.8% versus 51.2% in the original population. At multivariate analysis, International Society of Urological Pathology grade group, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.02). The PA of the nomogram was identical to the original model (82.0%); the model showed an optimal calibration curve. The best nomogram's cutoff was 55%. In the DCA, the nomogram revealed clinical net benefit when the threshold nomogram probabilities were ≥20%. The retrospective design is a major limitation. CONCLUSIONS: The original nomogram exhibited excellent characteristics on external validation. The incidence of a false negative scan can be reduced if PSMA-PET is performed when the predicted probability is ≥20%. PATIENT SUMMARY: A nomogram has been developed to predict prostate-specific membrane antigen/positron emission tomography (PSMA-PET) results for recurrent prostate cancer (PCa). The nomogram represents an easy tool in the decision-making process of recurrent PCa.

Comparison of prostate cancer detection rate at targeted biopsy of hub and spoke centers mpMRI: experience matters.

BACKGROUND: Latest changes in European guidelines on prostate cancer determined a widespread of multiparametric magnetic resonance imaging (mpMRI) even in less experienced centers due to an increased demand. This could decrease diagnostic accuracy of targeted biopsy (TB) since image interpretation can be challenging and requires adequate and supervised training. Therefore we aimed to evaluate the prostate cancer (PCa) detection rate on TB according to mpMRI center's volume and experience. METHODS: We retrospectively analyzed data of 737 patients who underwent mpMRI-TB at our institution. Patients were stratified according to mpMRI center: Hub (high volume >100 exams/year with dedicated radiologists and supervised training) and Spoke center (low volume <100 exams/year without dedicated radiologists and/or supervised training). Detection rate of PCa at TB and possible predictors of clinically significant PCa (csPCa) at TB. Differences in detection rate were explored using Chi-square test. Predictors of csPCa were evaluated through uni and multivariable logistic regression. The adjustment for casemix included: age, PSA, mpMRI center, lesion's location, PSA density, PI-RADS score and index lesion's size. RESULTS: Four hundred forty-nine (60.9%) and 288 (39.1%) patients underwent mpMRI at a Hub or Spoke center, respectively. Hub group had higher detection rate for both any (60.3% vs. 48.1%) and csPCa (46.9% vs 38.7%; all P≤0.001). After stratifying for PI-RADS score, Hub group had higher detection rate for PI-RADS score 3 (csPCA 25.2% vs. 15.7%; p 0.04) and 4 (csPCa 65.7% vs. 45.7%; P=0.001). At multivariable analyses, receiving an mpMRI scan at a Spoke center was an independent predictor for csPCa on TB (OR 0.65; P=0.04). CONCLUSIONS: mpMRI performed in Hub centers provided a significantly higher PCa yield on TB. A dedicated team of experienced radiologist, a supervised training for mpMRI and a central revision of mpMRI performed in non-experienced centres are essential to avoid unnecessary and potentially harmful procedures.

Site-specific concordance of targeted and systematic biopsy cores at the index lesion on multiparametric magnetic resonance: can we spare the double-tap?

PURPOSE: To define the impact of systematic biopsy (SB) cores directed in the same area of index lesion in patients undergoing targeted biopsy (TB) and SB for prostate cancer (PCa) suspicion. METHODS: We retrospectively analyzed data of biopsy-naïve patients with one single suspicious lesion at mpMRI who underwent TB plus SB at our institution between January 2015 and September 2021. A convenient sample of 336 patients was available for our analyses. The primary outcome was to evaluate the impact of overlapping SB cores directed to the index lesion at mpMRI. The secondary outcome was to evaluate the SB cores concordance in terms of highest Gleason Score Detection with TB cores. RESULTS: 56% of patients were found to have site-specific concordance. SB cores determined disease upgrade in 22.1% patients. Thirty-one (16.4%) site-concordant patients experienced upgrade through overlapping SB cores, while 149 (79.3%) had no benefit by SB cores, and 8 (4.3%) patients had the worst ISUP at TB cores. 50% of the patients with negative-TB were upgraded to insignificant PCa, and 17.5% was upgraded from negative to unfavorable-intermediate- or high-risk PCa. Overall, 14 (19.4%) patients were also upgraded from ISUP 1 on TB to csPCa, with 28.5% of these harboring high-risk PCa. In csPCas at TB, 9 (12.5%) patients were upgraded from intermediate- to high-risk disease by SB. CONCLUSIONS: TB alone consents to identify worst ISUP PCa in vast majority of patients scheduled for biopsy. A non-negligible number of patients are upgraded via-SB cores, including also index lesion overlapping cores. Omitting these cores might lead to a suboptimal patient management.

Role of Local and/or Metastasis-directed Therapy in Patients with Hormone-sensitive M1a Prostate Cancer-A Systematic Review.

CONTEXT: It remains unclear whether men with hormone-sensitive prostate cancer (PCa) metastasized to nonregional lymph nodes (M1a) benefit from prostate-directed therapy (PDT) and/or metastasis-directed therapy (MDT). OBJECTIVE: To systematically summarize the literature regarding oncological outcomes of de novo and recurrent M1a PCa patients treated with PDT and/or MDT. EVIDENCE ACQUISITION: We searched Medline (Ovid), Embase, and Scopus according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines for reports on oncological outcomes of de novo or recurrent hormone-sensitive M1a PCa patients treated with PDT (radical prostatectomy or radiotherapy) and/or MDT (nodal radiotherapy or salvage lymph node dissection) with or without androgen deprivation therapy. A descriptive data synthesis and a methodological quality assessment were performed to evaluate the impact of PDT and/or MDT on survival in M1a PCa patients. EVIDENCE SYNTHESIS: A total of 6136 articles were screened and 24 studies were included in this systematic review. In de novo M1a PCa patients, PDT was associated with improved oncological outcomes compared with no PDT. In recurrent M1a PCa, MDT could delay the need for systemic treatment in a selection of patients, but high-level evidence from prospective phase III randomized controlled trials is still awaited. CONCLUSIONS: This systematic review summarized the limited literature data on the management of M1a PCa. Subgroup analyses suggest a role for PDT plus systemic therapy in de novo M1a PCa. MDT to distant nodal metastases delayed the need for systemic therapy in recurrent disease, but robust data are lacking. The predominantly retrospective nature of the included studies and significant heterogeneity in study designs limit the strength of evidence. PATIENT SUMMARY: We reviewed the treatment of patients with prostate cancer that has spread to lymph nodes outside the pelvis without metastases in other organ systems. There is evidence that treatment of the primary prostate tumor improves outcomes in well-selected patients and that treatment targeting distant lymph node metastases can delay the start of systemic treatment.

3D renal model for surgical planning of partial nephrectomy: A way to improve surgical outcomes.

Objective: to evaluate the impact of 3D model for a comprehensive assessment of surgical planning and quality of partial nephrectomy (PN). Materials and methods: 195 patients with cT1-T2 renal mass scheduled for PN were enrolled in two groups: Study Group (n= 100), including patients referred to PN with revision of both 2D computed tomography (CT) imaging and 3D model; Control group (n= 95), including patients referred to PN with revision of 2D CT imaging. Overall, 20 individuals were switched to radical nephrectomy (RN). The primary outcome was the impact of 3D models-based surgical planning on Trifecta achievement (defined as the contemporary absence of positive surgical margin, major complications and ≤30% postoperative eGFR reduction). The secondary outcome was the impact of 3D models on surgical planning of PN. Multivariate logistic regressions were used to identify predictors of selective clamping and Trifecta's achievement in patients treated with PN (n=175). Results: Overall, 73 (80.2%) patients in Study group and 53 (63.1%) patients in Control group achieved the Trifecta (p=0.01). The preoperative plan of arterial clamping was recorded as clampless, main artery and selective in 22 (24.2%), 22 (24.2%) and 47 (51.6%) cases in Study group vs. 31 (36.9%), 46 (54.8%) and 7 (8.3%) cases in Control group, respectively (p<0.001). At multivariate logistic regressions, the use of 3D model was found to be independent predictor of both selective or super-selective clamping and Trifecta's achievement. Conclusion: 3D-guided approach to PN increase the adoption of selective clamping and better predict the achievement of Trifecta.

Short Time Delay Between Previous Prostate Biopsy for Prostate Cancer Assessment and Holmium Laser Enucleation of the Prostate Correlates with Worse Perioperative Outcomes.

BACKGROUND: No data are available regarding the impact of time between a previous transrectal prostate biopsy (PB) and holmium laser enucleation of the prostate (HoLEP) on perioperative outcomes. OBJECTIVE: To evaluate the impact of time from PB to HoLEP on perioperative outcomes. DESIGN, SETTING, AND PARTICIPANTS: A total of 172 consecutive patients treated with HoLEP within 12 mo of a single previous transrectal PB at two tertiary centers were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were stratified into two groups according to the median time from PB to HoLEP (namely, ≤6 and >6 mo). The primary outcome was intraoperative complications. Multivariate logistic regressions were used to identify the predictors of intraoperative complications. Linear regressions were used to test the association between the time from PB to HoLEP and intraoperative complications, enucleation efficiency, and enucleation time. RESULTS AND LIMITATIONS: In total, 93 (54%) and 79 (46%) patients had PB ≤ 6 and >6 mo before HoLEP, respectively. Patients in PB ≤ 6 mo group experienced higher rates of intraoperative complications than those in PB > 6 mo group (14% vs 2.6%, p = 0.04). At multivariable analysis, time between PB and HoLEP was an independent predictor of intraoperative complications (odds ratio: 0.74; 95% confidence interval: 0.6-0.9; p = 0.006). Finally, the risk of intraoperative complications reduced by 1.5%, efficiency of enucleation increased by 4.1%, and enucleation time reduced by 1.7 min for each month passed from PB to HoLEP (all p ≤ 0.006). Selection of patients with only one previous PB represents the main limitation. CONCLUSIONS: The time from PB to HoLEP of ≤6 mo is associated with a higher risk of intraoperative complications, lower enucleation efficacy, and longer enucleation time. PATIENT SUMMARY: Patients with a prostate biopsy (PB) ≤6 mo before holmium laser enucleation of the prostate (HoLEP) had significantly worse outcomes than those with a PB > 6 mo before HoLEP.

Long-term outcomes of Holmium laser enucleation of prostate and predictive model for symptom recurrence.

INTRODUCTION AND OBJECTIVES: Holmium laser enucleation of prostate (HoLEP) represents one of the most studied surgical techniques for benign prostatic hyperplasia (BPH). Its efficacy in symptom relief has been widely depicted. However, few evidence is available regarding the possible predictors of symptom recurrence. We aimed to evaluate long-term outcomes, symptom recurrence rate, and predictors in patients that underwent HoLEP. MATERIALS AND METHODS: We retrospectively analyzed data from patients that consecutively underwent HoLEP for BPH from 2012 to 2015 at two tertiary referral centers. Functional outcomes were evaluated by uroflowmetry parameters and International Prostate Symptom Score (IPSS) questionnaire administration at follow-up visits at 12, 24, and 60 months. The primary outcome was the symptomatic patients' rate presenting lower urinary tract symptoms (LUTS) after 60 months from surgery, defined as in case of one or more of the following: IPSS more than 7, post voidal residue (PVR) more than 20 ml, need for medical therapy for LUTS or redo surgery for bladder outlet obstruction. Multivariable logistic regression analyses evaluated predictors for being symptomatic at follow-up. Covariates consisted of: preoperative peak flow rate (PFR), PVR, and IPSS, prostate volume, age (all as continuous), and surgical technique. RESULTS: A total of 567 patients were available for our analyses. Median prostate volume was 80cc, with a median PFR of 8 ml/s and median PVR of 100cc. One hundred and twenty-five (22%) patients were found to be symptomatic at follow-up. Redo surgery was needed for 25 (4.4%) patients. After adjusting for possible confounders, an increase in preoperative PVR (odds ratio [OR] 1.005) and IPSS (OR 1.12) resulted as independent predictors for symptom recurrence (all p < 0.001). CONCLUSIONS: HoLEP can provide durable symptom relief regardless of the chosen technique. Patients with an important preoperative symptom burden or a high PVR should be carefully counseled on the risk of symptom recurrence.

Novel Volumetric and Morphological Parameters Derived from Three-dimensional Virtual Modeling to Improve Comprehension of Tumor's Anatomy in Patients with Renal Cancer.

BACKGROUND: Three-dimensional (3D) models improve the comprehension of renal anatomy. OBJECTIVE: To evaluate the impact of novel 3D-derived parameters, to predict surgical outcomes after robot-assisted partial nephrectomy (RAPN). DESIGN, SETTING, AND PARTICIPANTS: Sixty-nine patients with cT1-T2 renal mass scheduled for RAPN were included. Three-dimensional virtual modeling was achieved from computed tomography. The following volumetric and morphological 3D parameters were calculated: VT (volume of the tumor); VT/VK (ratio between tumor volume and kidney volume); CSA3D (ie, contact surface area); UCS3D (contact to the urinary collecting system); Tumor-Artery3D: tumor's blood supply by tertiary segmental arteries (score = 1), secondary segmental artery (score = 2), or primary segmental/main renal artery (scoren = 3); ST (tumor's sphericity); ConvT (tumor's convexity); and Endophyticity3D (ratio between the CSA3D and the global tumor surface). INTERVENTION: RAPN with a 3D model. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three-dimensional parameters were compared between patients with and without complications. Univariate logistic regression was used to predict overall complications and type of clamping; linear regression was used to predict operative time, warm ischemia time, and estimated blood loss. RESULTS AND LIMITATIONS: Overall, 11 (15%) individuals experienced overall complications (7.2% had Clavien ≥3 complications). Patients with urinary collecting system (UCS) involvement at 3D model (UCS3D = 2), tumor with blood supply by primary or secondary segmentary arteries (Tumor-Artery3D = 1 and 2), and high Endophyticity3D values had significantly higher rates of overall complications (all p ≤ 0.03). At univariate analysis, UCS3D, Tumor-Artery3D, and Endophyticity3D are significantly associated with overall complications; CSA3D and Endophyticity3D were associated with warm ischemia time; and CSA3D was associated with selective clamping (all p ≤ 0.03). Sample size and the lack of interobserver variability are the main limits. CONCLUSIONS: Three-dimensional modeling provides novel volumetric and morphological parameters to predict surgical outcomes after RAPN. PATIENT SUMMARY: Novel morphological and volumetric parameters can be derived from a three-dimensional model to describe surgical complexity of renal mass and to predict surgical outcomes after robot-assisted partial nephrectomy.

Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy.

BACKGROUND: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown. OBJECTIVE: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM. RESULTS AND LIMITATIONS: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%. CONCLUSIONS: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials. PATIENT SUMMARY: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

The Impact of PSMA-PET on Oncologic Control in Prostate Cancer Patients Who Experienced PSA Persistence or Recurrence.

Background: Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is currently recommended to restage prostate cancer (PCa) and to guide the delivery of salvage treatments. We aim to evaluate the oncologic outcomes of patients with recurrent PCa who received PSMA-PET. Methods: 324 hormone-sensitive PCa with PSA relapse after radical prostatectomy who underwent PSMA-PET in three high-volume European Centres. Patients have been stratified as pre-salvage who never received salvage treatments (n = 134), and post-salvage, including patients who received previous salvage therapies (n = 190). Patients with oligorecurrent (≤3 lesions), PSMA-positive disease underwent PSMA-directed treatments: salvage radiotherapy (sRT) or Metastases-directed therapy (MDT). Patients with polirecurrent (>3 lesions) PSMA-positive disease were treated with systemic therapy. Patients with negative PSMA-PET were treated with sRT or systemic therapies or observation. The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were: Metastases-free survival (MFS) and Castration Resistant Pca free survival (CRPC-FS). Results: median follow up was 23 months. In the pre-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 66.2% vs. 38.9%, 95.2% vs. 73.7% and 94.9% vs. 93.1% in patients with negative vs. positive PSMA-PET, respectively (all p ≥ 0.2). In the post-salvage setting, the PFS, MFS and CRPC-FS estimates at 3 years were 59.5% vs. 29.1%, 92.7% vs. 65.1% and 98.8% vs. 88.8% in patients with negative vs. positive PSMA-PET, respectively (all p ≤ 0.01). At multivariable analyses, a positive PSMA-PET was an independent predictor of progression (HR = 2.15) and metastatic disease (HR 2.37; all p ≤ 0.03). Conclusion: PSMA-PET in recurrent PCa detects the site of recurrence guiding salvage treatments and has a prognostic role in patients who received previous salvage treatments.

Interpreting nephrometry scores with three-dimensional virtual modelling for better planning of robotic partial nephrectomy and predicting complications.

OBJECTIVE: 3D models are increasingly used as additional preoperative tools for renal surgery. We aim to evaluate the impact of 3D renal models in the assessment of PADUA, RENAL, Contact Surface Area (CSA) and Arterial Based Complexity (ABC) for the prediction of complications after Robot assisted Partial Nephrectomy (RAPN). METHODS AND MATERIALS: Overall, 57 patients with T1 and 1 patient with T2 renal mass referred to RAPN, were prospectively enrolled. 3D virtual modelling was obtained from 2D computed tomography (CT). Two radiologists recorded PADUA2D, RENAL2D, CSA2D and ABC2D by evaluation of 2D images; two bioengineers recorded PADUA3D, RENAL3D, CSA3D and ABC3D by evaluation of the 3D model, using MeshMixer software. To evaluate the concordance between 2D and 3D nephrometry scores, Cohen's j coefficient was calculated. Receiver-operating characteristic (ROC) curves were generated to evaluate the accuracy of 3D and 2D nephrometry scores to predict overall complications. Finally, the impact of 3D model on clamping approach during RAPN was compared to 2D imaging. RESULTS: PADUA3D, RENAL3D, CSA3D and ABC3D scores had a significant different distribution compared to PADUA2D, RENAL2D, CSA2D and ABC2D (all p≤0.03). 2D nephrometry scores may be unchanged, reduced or increased after assessment by 3D models: CSA3D, PADUA3D, RENAL3D and ABC3D were reduced in14%, 26%, 29% and 16% and increased in 16%, 36%, 38% and 29% of cases, respectively. At ROC curve analysis, PADUA3D, RENAL3D and ABC3D showed were significantly better accuracy to predict complications compared to PADUA2D, RENAL2D and ABC2D. PADUA3D (OR: 1.66), RENAL3D (OR: 1.69) and ABC3D (OR: 2.44) revealed a significant correlation with postoperative complications (all P ≤0.03). CONCLUSION: Nephrometry scores calculated via 3D models predict complications after RAPN with higher accuracy than conventional 2D imaging.