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Purpose: We assessed the diagnostic yield of consecutive transperineal targeted biopsy of multiparametric magnetic resonance imaging index lesion and secondary lesion and additive systematic biopsy in patients who received combined targeted biopsy+systematic biopsy of prostate., Materials and Methods: Of 1,467 patients with targeted biopsy+systematic biopsy, analyses were restricted to 571 patients with index lesion+secondary lesion, Prostate Imaging-Reporting and Data System score ≥3. Index lesion was defined as having the greatest Prostate Imaging-Reporting and Data System score and/or lesion volume as opposed to secondary lesion. We retrospectively compared clinically significant prostate cancer rates (ie, Gleason Grade Group ≥2) between index lesion+secondary lesion and index lesion+secondary lesion+systematic biopsy. Subgroup analyses in men with ipsilateral index lesion+secondary lesion focused on contralateral systematic biopsy. Multivariable logistic regression analyses to predict any clinically significant prostate cancer included age, previous biopsies, prostate specific antigen density, respective index lesion/secondary lesion volumes, side relation, Prostate Imaging-Reporting and Data System strata, and number of targeted biopsy and systematic biopsy cores., Results: Clinically significant prostate cancer rates for index lesion+secondary lesion vs index lesion+secondary lesion+systematic biopsy were 38% vs 42% ( P = .2) at expense of significantly higher median number of biopsy cores (9 vs 25, P < .001). In the subgroup with ipsilateral index lesion+secondary lesion (n = 236), contralateral systematic biopsy detected clinically significant prostate cancer in 17%. In the narrower subgroup with ipsilateral index lesion+secondary lesion (n = 131) without any clinically significant prostate cancer, contralateral systematic biopsy detected clinically significant prostate cancer in 3.8%. Multivariable logistic regression analyses confirmed contralateral systematic biopsy as independent predictor, but performed similarly without systematic biopsy information (area under the curve 87.1% vs 86.6%)., Conclusions: Targeted biopsy of secondary lesion should be included in targeted biopsy protocols due to added diagnostic information. However, for targeted biopsy of index lesion+secondary lesion additional systematic biopsy is of limited informative value in terms of overall clinically significant prostate cancer detection. However, when index lesion+secondary lesion are ipsilateral, contralateral systematic biopsy should be recommended for purpose of prostate lobe information. Our results indicate great potential to reduce systematic biopsy cores and associated potential morbidity, and warrant prospective evaluation.

Purpose: We assessed whether sampling of the transitional zone can be spared in patients with exclusively peripheral prostate cancer (PCa)-suspicious multiparametric magnetic resonance imaging (mpMRI) lesions who undergo combined mpMRI targeted (TBx) and systematic prostate biopsies (SBx)., Materials and Methods: Of 1,685 patients who underwent extended SBx including transitional zone sampling and had TBx of ≥1 lesion in the peripheral and/or transitional zone, we selected 863 patients with exclusively peripheral PCa-suspicious lesions and negative transitional zone mpMRI. Clinically significant PCa (csPCa) was defined as Gleason score (GS) ≥3+4. Within the selected cohort we performed a retrospective head-to-head comparison of csPCa detection rates between biopsy protocols: A) combination of peripheral TBx plus extended SBx including transitional zone sampling vs B) peripheral TBx plus SBx without any transitional zone sampling. Analyses were complemented with multivariable logistic regression models (LRMs) in the total cohort for predicting csPCa in SBx transitional zone sampling., Results: Compared to the extended protocol (A), omission of systematic transitional zone sampling (B) yielded similar PCa detection for csPCa (48% vs 47%) and GS 3+3 (21% vs 20%). Only 2.0% csPCa was additionally detected with transitional zone SBx sampling (A). LRM confirmed that intraprostatic zonal distribution of mpMRI lesions independently influences csPCa detection rates of transitional zone SBx sampling., Conclusions: A peripheral TBx plus SBx without any transitional zone sampling protocol (B) yields similar csPCa detection rates as the standard extended protocol (A) but may reduce biopsy-related morbidity. This zone-dependent biopsy strategy warrants prospective evaluation to optimize the extent of systematic biopsies in presence of suspicious mpMRI lesions.

Purpose: We sought to address the impact of preoperative prostate specific membrane antigen (PSMA) positron emission tomography (PET) findings prior to radical prostatectomy and pelvic lymph node dissection on biochemical recurrence and time to adjuvant or salvage treatment., Materials and Methods: Between 2013 and 2017, 64 intermediate and 166 high risk (230) prostate cancer patients received 68 Ga-PSMA-11 PET followed by radical prostatectomy and pelvic lymph node dissection. Biochemical recurrence-free and therapy-free survivalwere determined. For all time-to-event analyses, univariable and multivariable Cox proportional hazards models and univariable Kaplan-Meier analyses were applied, with a significance threshold of p <0.05., Results: The overall sensitivity, specificity, positive predictive value and negative predictive value of PSMA PET for pN1 disease was 48.5%, 95.7%, 82.1% and 82.2%, respectively. Median followup was 30.2 months. Biochemical recurrence occurred in 50.4% (116) of patients and adjuvant or salvage treatment was performed in 46.5% (107). Worst biochemical recurrence-free and therapy-free survival was observed in pN1 patients who also exhibited PSMA PET positive lymph node, followed by pN1 patients without PSMA PET positive lymph node and patients without evidence of lymph node metastasis on histology and PSMA PET (median biochemical recurrence-free survival 1.7 vs. 7.5 vs. >36 months, median therapy-free survival 2.6 vs. 8.9 vs. >36 months)., Conclusions: Patients with positive lymph node on PSMA PET prior to radical prostatectomy have to expect early biochemical recurrence and adjuvant/salvage therapy, despite thorough pelvic lymph node dissection. Therefore, results from PSMA PET can be used for patients' consultation and more stringent followup as well as for planning of neoadjuvant/adjuvant therapy.

Purpose: We analyzed the number of multiparametric magnetic resonance imaging targeted biopsy cores per lesion needed to detect prostate cancer in patients treated with radical prostatectomy., Materials and Methods: Analyses focused on targeted biopsy of magnetic resonance imaging lesions suspicious for prostate cancer with a PI-RADS® (Prostate Imaging Reporting and Data System) score of 3 or greater and consecutive radical prostatectomy. Descriptive statistics included the frequency/proportion and IQR. Multivariable logistic regression analyses on the per lesion level were used to predict the number of targeted biopsies with prostate cancer., Results: In the total cohort of 771 radical prostatectomy cases 437 (57%) and 334 (43%) were systematic transrectal ultrasound guided biopsy naïve or had 1 or more prior negative systematic transrectal ultrasound guided biopsies, respectively. A maximum PI-RADS score of 3, 4 and 5 was present in 67 (8.7%), 567 (74%) and 137 patients (18%), respectively. A total of 1,459 multiparametric magnetic resonance imaging lesions suspicious for prostate cancer were identified for analysis. Prostate cancer was detected based on an initial, second, third, or fourth or greater targeted biopsy in 79%, 92%, 98% and 100% of cases, respectively. The rate of prostate cancer detection on the first targeted biopsy core increased with higher PI-RADS scores of 3, 4 and 5 (67%, 79% and 87%, respectively). The number of prior negative systematic transrectal ultrasound guided biopsies and pathological tumor stage emerged as independent predictors on multivariate analysis, addressing the need for 2 or more targeted biopsy cores to detect clinically significant prostate cancer., Conclusions: Radical prostatectomy based analyses demonstrated that most cancers could be detected by 2 targeted biopsies only while in a minority of cases 3 or more targeted biopsies were necessary. Such findings might indicate that the targeted biopsy procedure and the related technology have improved, especially in patients with intermediate/high risk prostate cancer.

Purpose: Based on findings in transrectal ultrasound guided biopsy series standard sampling of the prostate targets the posterior/peripheral zone. However, a substantial proportion of lesions that are prostate cancer suspicious and PI-RADS™ (Prostate Imaging Reporting and Data System) 3 or greater on magnetic resonance imaging is located in the anterior segment of the prostate, requiring deeper placement and targeting of the biopsy needle., Materials and Methods: Overall 1,161 patients underwent magnetic resonance imaging/ultrasound fusion guided targeted biopsy. Prostate cancer suspicious lesions on magnetic resonance imaging were dichotomized into anterior vs posterior prostate segments. Patients were stratified by the number of prior negative systematic biopsy sessions. Descriptive statistics included the frequency and proportion of multiparametric magnetic resonance imaging findings and corresponding histological results., Results: Targeted biopsy was performed in 513 patients (44%) who were systematic biopsy naïve, 396 (34%) with 1 prior negative systematic biopsy and 252 (22%) with 2 or more prior negative systematic biopsies. When patients were stratified by the number of prior systematic biopsy sessions, the proportion with exclusively anterior, PI-RADS 3 or greater lesions on magnetic resonance imaging increased from 3.5% to 9.1% (p = 0.006). Unfavorable 3 + 4 and 4 + 3 or greater primary Gleason patterns were identified in exclusively anterior vs posterior lesions in 31% vs 21% of the 448 patients, of whom 64 had exclusively anterior and 384 had posterior PI-RADS 3 or greater lesions, respectively, on magnetic resonance imaging. Multivariable logistic regression analyses confirmed these findings., Conclusions: After multiple previous negative systematic biopsy sessions the proportion of anterior lesions on magnetic resonance imaging increased. Such lesions harbored a greater amount of unfavorable prostate cancer. Therefore, image guidance for precise targeting should be considered, especially after initially negative transrectal ultrasound guided systematic biopsy., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Experimental evidence suggests that phosphodiesterase type 5 inhibitors may suppress tumor growth, postpone metastasis and prolong survival, but clinical data are lacking. We studied the effect of phosphodiesterase type 5 inhibitors on biochemical recurrence after radical prostatectomy for prostate cancer., Materials and Methods: The study was comprised of 4,752 consecutive patients with localized prostate cancer treated with bilateral nerve sparing radical prostatectomy between January 2000 and December 2010. Of these patients 1,110 (23.4%) received phosphodiesterase type 5 inhibitors postoperatively while 3,642 (76.6%) did not. The risk of biochemical recurrence was compared between the phosphodiesterase type 5 inhibitor group and the nonphosphodiesterase type 5 inhibitor group. Cox multivariate proportional hazard models and confidence intervals were used to estimate the hazard ratio of biochemical recurrence associated with phosphodiesterase type 5 inhibitor use. Propensity score matched analysis was performed., Results: Median followup was 60.3 months (IQR 36.7-84.5). Five-year biochemical recurrence-free survival estimates in the phosphodiesterase type 5 inhibitor vs nonphosphodiesterase type 5 inhibitor groups were 84.7% (95% CI 82.1-87.0) and 89.2% (95% CI 88.1-90.3), respectively (p=0.0006). Multivariate regression analysis showed that phosphodiesterase type 5 inhibitor use was an independent risk factor for biochemical recurrence (HR 1.38, 95% CI 1.11-1.70, p=0.0035) and this was also true after propensity score matching., Conclusions: Contrary to experimental data, the use of phosphodiesterase type 5 inhibitors after radical prostatectomy may adversely impact biochemical recurrence. Further studies are needed to validate our results., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: The prognostic significance of a tertiary Gleason pattern in the radical prostatectomy specimen is controversial. We tested the impact of a tertiary Gleason pattern on adverse histopathological features and biochemical recurrence rates after radical prostatectomy., Materials and Methods: We assessed data on 11,226 consecutive patients treated with radical prostatectomy at our institution between June 2007 and February 2013. We compared 2,396 patients with (22.4%) and 8,260 without (77.5%) a tertiary Gleason pattern for adverse histopathological features (extraprostatic extension, seminal vesicle invasion, positive surgical margins and lymph node invasion) using the chi-square test. The effect of a tertiary Gleason pattern on biochemical recurrence was tested in univariable and multivariable models. Subanalyses were then done for different radical prostatectomy Gleason groups (6 or less, 3 + 4 and 4 + 3)., Results: A tertiary Gleason pattern was statistically significantly associated with all evaluated histopathological parameters (each p <0.001). It was an independent predictor of biochemical recurrence (HR 1.43, p <0.001). On subanalysis only a tertiary Gleason pattern independently predicted biochemical recurrence in the patient cohort with a radical prostatectomy Gleason score of 3 + 4 and 4 + 3. However, it failed to attain independent predictor status in patients with a radical prostatectomy Gleason score of 6 or less., Conclusions: A tertiary Gleason pattern is a significant and independent predictor of biochemical recurrence after radical prostatectomy with the strongest prognostic effect in cases with Gleason scores 3 + 4 and 4 + 3. Therefore, a tertiary Gleason pattern should be recorded in the pathological report., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We tested the relationship between caseload and total hospital charges after stratifying by minimally invasive and open radical prostatectomy., Materials and Methods: We evaluated 1,188 vs 3,354 men treated with minimally invasive vs open radical prostatectomy in the Florida Hospital Inpatients data file in 2008. Caseload was defined as the count of procedures performed by each surgeon between the study start on January 1, 2008 and the date of each procedure. Patients were divided into tertiles based on their procedure specific caseload. Univariate and multivariate analysis was done to address the relation between caseload and total hospital charges for the minimally invasive and open procedures. Covariates were patient age, race, comorbidity, and length of stay., Results: Median total hospital charges for minimally invasive and open radical prostatectomy were $33,234 and $33,674, respectively (p=0.03). Median total hospital charges in the low, intermediate and high minimally invasive vs open procedure caseload tertiles were $41,765, $34,799 and $28,780 vs $35,642, $34,726 and $32,726, respectively. On multivariate analysis with the high minimally invasive caseload tertile as the reference category the increments of the probability of charges in excess of the 2008 median of $33,588 were 3.9 and 8.1-fold for the intermediate and low caseload minimally invasive procedures, and 2.5, 3.6 and 2.8-fold for the high, intermediate and low caseload open procedures, respectively (each p<0.001)., Conclusions: Overall median total hospital charges are virtually the same for minimally invasive and open radical prostatectomy. However, total hospital charges for the minimally invasive procedure have a more sensitive caseload effect, as evidenced by the wider distribution of the median of minimally invasive caseload specific total hospital charges vs that of open radical prostatectomy. The high caseload minimally invasive procedure resulted in the lowest total hospital charges relative to all other minimally invasive and open radical prostatectomy categories., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Radical prostatectomy is the standard of care for localized prostate cancer. Numerous previous reports show the relationship between surgical experience and various outcomes. We examined the effect of surgical experience on complications and transfusion rates, and determined individual surgeon annual caseload trends in a contemporary radical prostatectomy cohort., Materials and Methods: We analyzed annual caseload temporal trends in 34,803 patients who underwent surgery between 1999 and 2008 in Florida. Logistic regression models controlled for clustering among surgeons addressed the relationship of surgical experience, defined as the number of radical prostatectomies done since January 1, 1999 until each radical prostatectomy, with complications and transfusions., Results: During the study period the proportion of surgeons in the high annual caseload tertile (24 radical prostatectomies or greater yearly) and the proportion of patients treated by those surgeons increased from 5% to 10% and from 20% to 55%, respectively. Conversely complication and transfusion rates decreased from 14.3% to 9.2% and 12.6% to 6.9%, respectively. Radical prostatectomies done by surgeons in the high surgical experience tertile (86 or greater radical prostatectomies) decreased the risk of any complication by 33% and of any transfusion by 30% vs those in patients operated on by surgeons in the low surgical experience tertile (27 or fewer radical prostatectomies)., Conclusions: The proportion of surgeons in the high annual caseload tertile and the proportion of patients treated by these surgeons steadily increased during the last decade. Complication and transfusion rates decreased with time. The implications of these encouraging findings may result in improved outcomes in patients with surgically managed prostate cancer., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: A positive surgical margin after radical prostatectomy is considered an adverse prognostic feature. However, few groups have explored the potential interaction between surgical margin status and other cancer characteristics, specifically pathological stage. We addressed the first degree of interaction between positive surgical margins and other established adverse predictors of biochemical recurrence after radical prostatectomy., Materials and Methods: We used univariate and multivariate analysis to test the effect of surgical margin status on biochemical recurrence in 4,490 patients treated at a single institution between 1992 and 2008. We systematically tested all first-degree interactions between surgical margin status, and pretreatment prostate specific antigen, pT and pN stage, and radical prostatectomy Gleason sum. If interactions were significant, we quantified the effect on the biochemical recurrence rate., Results: Overall 850 patients (18.9%) had positive surgical margins. In those with negative vs positive surgical margins the 5-year biochemical recurrence-free survival rate was 95% vs 83%, 74% vs 62% and 47% vs 29% for pT2, pT3a and pT3b disease, respectively. In multivariate models only the pT stage-surgical margin status interaction achieved independent predictor status (p = 0.003). Negative vs positive surgical margin multivariate HRs were 1 vs 2.9, 2.3 vs 4.3 and 4.1 vs 5.6 in pT2, pT3a and pT3b cases, respectively., Conclusions: Compared to negative surgical margins, positive surgical margins increase the absolute biochemical recurrence 5-year rate by 12% to 18%. More importantly, positive surgical margins may substantially worsen the prognosis beyond that of the original pathological disease stage., (Copyright © 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: Inguinal hernia is considered one of the major morbidities after radical prostatectomy. We compared inguinal hernia repair rates in patients treated with radical prostatectomy for localized prostate cancer relative to those of 2 nonsurgically treated groups of patients, namely individuals who underwent prostate biopsy or transurethral resection of the prostate, and a surgically treated group of patients who underwent pelvic lymph node dissection, within a large North American database., Materials and Methods: Using the Quebec Health Plan database we identified 5,478 men treated with radical prostatectomy vs 6,933, 7,697 and 532 who underwent prostate biopsy, transurethral resection of the prostate or pelvic lymph node dissection, respectively, between 1990 and 2000. Kaplan-Meier plots graphically explored inguinal hernia repair rates. Univariable and multivariable Cox regression analyses examined variables associated with inguinal hernia repair after either group. Covariates consisted of age, year of treatment and the Charlson comorbidity index., Results: The 1, 2, 5 and 10-year inguinal hernia repair rates after radical prostatectomy were 4.4%, 6.7%, 11.7% and 17.1%, respectively. For the same points after prostate biopsy the rates were 1.7%, 2.9%, 6.1% and 9.8% vs 1.7%, 2.6%, 5.5% and 9.2%, respectively, after transurethral resection of the prostate, and 0.8%, 2.4%, 4.9% and 9.3% after pelvic lymph node dissection (pairwise log rank tests p <0.001). On multivariable Cox regression analyses the rate of inguinal hernia repair was 1.9, 2.1 and 1.7-fold higher for patients who underwent radical prostatectomy vs prostate biopsy, transurethral resection of the prostate and pelvic lymph node dissection, respectively (all p <0.001)., Conclusions: Radical prostatectomy predisposes to higher inguinal hernia repair rates than in the 3 examined control groups. A higher rate of inguinal hernia repair after radical prostatectomy warrants consideration in the discussion of radical prostatectomy perioperative complications., (2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)