Prostate-specific membrane antigen radioguided surgery with negative histopathology: an in-depth analysis.

PURPOSE: To identify reasons for negative histopathology of specimens from prostate-specific membrane antigen (PSMA) radioguided surgery (PSMA-RGS) in recurrent prostate cancer (PCa) after prostatectomy. METHODS: Of 302 patients who underwent PSMA-RGS, 17 (5.6%) demonstrated a negative histopathology. Preoperative data, PSMA PET, PSMA SPECT, and follow-up information were analyzed retrospectively to differentiate true/false positive (TP/FP) from true/false negative (TN/FN) lesions. RESULTS: The median prostate-specific antigen at PET was 0.4 ng/ml (interquartile range [IQR] 0.3-1.2). Twenty-five index lesions (median short axis 7 mm, IQR 5-8; median long-axis 12 mm, IQR 8-17) had a median SUVmax of 4 (IQR 2.6-6; median PSMA expression score 1, IQR 1-1). Six lesions were TP, twelve were FP, one was TN, and six remained unclear. All TP lesions were in the prostatic fossa or adjacent to the internal iliac arteries. Three suspected local recurrences were FP. All FP lymph nodes were located at the distal external iliac arteries or outside the pelvis. A low PSMA-expressing TN node was identified next to a common iliac artery. Unclear lesions were located next to the external iliac arteries or outside the pelvis. CONCLUSION: In most cases with a negative histopathology from PSMA-RGS, lesions were FP on PSMA PET. Unspecific uptake should be considered in low PSMA-expressing lymph nodes at the distal external iliac arteries or outside the pelvis, especially if no PSMA-positive lymph nodes closer to the prostatic fossa are evident. Rarely, true positive metastases were missed by surgery or histopathology.

PSA-density, DRE, and PI-RADS 5: potential surrogates for omitting biopsy?

OBJECTIVE: In contrast to other malignancies, histologic confirmation prior treatment in patients with a high suspicion of clinically significant prostate cancer (csPCA) is common. To analyze the impact of extracapsular extension (ECE), cT-stage defined by digital rectal examination (DRE), and PSA-density (PSA-D) on detection of csPCA in patients with at least one PI-RADS 5 lesion (hereinafter, "PI-RADS 5 patients"). MATERIALS AND METHODS: PI-RADS 5 patients who underwent MRI/Ultrasound fusion biopsy (Bx) between 2016 and 2020 were identified in our institutional database. Uni- and multivariable logistic-regression models were used to identify predictors of csPCA-detection (GGG ≥ 2). Risk models were adjusted for ECE, PSA-D, and cT-stage. Corresponding Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were calculated. RESULTS: Among 493 consecutive PI-RADS 5 patients, the median age and PSA was 69 years (IQR 63-74) and 8.9 ng/ml (IQR 6.0-13.7), respectively. CsPCA (GGG ≥ 2) was detected in 405/493 (82%); 36/493 patients (7%) had no cancer. When tabulating for PSA-D of > 0.2 ng/ml/cc and > 0.5 ng/ml/cc, csPCA was found in 228/253 (90%, PI-RADS5 + PSA-D > 0.2 ng/ml/cc) and 54/54 (100%, PI-RADS5 + PSA-D > 0.5 ng/ml/cc). Finally, a model incorporating PSA-D and cT-stage achieved an AUC of 0.79 (CI 0.74-0.83). CONCLUSION: In PI-RADS 5 patients, PSA-D and cT-stage emerged as strong predictors of csPCA at biopsy. Moreover, when adding the threshold of PSA-D > 0,5 ng/ml/cc, all PI-RADS 5 patients were diagnosed with csPCA. Therefore, straight treatment for PCA can be considered, especially if risk-factors for biopsy-related complications such as obligatory dual platelet inhibition are present.

Size of lymph-node metastases in prostate cancer patients undergoing radical prostatectomy: implication for imaging and oncologic follow-up of 2705 lymph-node positive patients.

BACKGROUND: Despite modern imaging modalities, lymph-node staging before radical prostatectomy (RP) remains challenging in patients with prostate cancer (PCa). The visibility of lymph-node metastases (LNMs) is critically influenced by their size. OBJECTIVE: This study aims to describe the distribution of maximal tumor diameters (i.e., size) in LNMs of pN1-PCa at RP and its consequences on visibility in preoperative imaging and oncological outcomes. DESIGN, SETTING, AND PARTICIPANTS: A total of 2705 consecutive patients with pN1-PCa at RP, harboring a cumulative 7510 LNMs, were analyzed. Descriptive and multivariable analyses addressed the risk of micrometastases (MM)-only disease and the visibility of LNMs. Kaplan-Meier curves and Cox analyses were used for biochemical recurrence-free survival (BCRFS) stratified for MM-only disease. RESULTS: The median LNM size was 4.5mm (interquartile range (IQR): 2.0-9.0 mm). Of 7510 LNMs, 1966 (26%) were MM (≤ 2mm). On preoperative imaging, 526 patients (19%) showed suspicious findings (PSMA-PET/CT: 169/344, 49%). In multivariable analysis, prostate-specific antigen (PSA) (OR 0.98), age (OR 1.01), a Gleason score greater than 7 at biopsy (OR 0.73), percentage of positive cores at biopsy (OR 0.36), and neoadjuvant treatment (OR 0.51) emerged as independent predictors for less MM-only disease (p < 0.05). Patients with MM-only disease compared to those harboring larger LNMs had a longer BCRFS (median 60 versus 29 months, p < 0.0001). CONCLUSION: Overall, 26% of LNMs were MM (≤ 2mm). Adverse clinical parameters were inversely associated with MM at RP. Consequently, PSMA-PET/CT did not detect a substantial proportion of LNMs. LNM size and count are relevant for prognosis.

Robot-assisted vs open retropubic radical prostatectomy: a propensity score-matched comparative analysis based on 15 years and 18,805 patients.

PURPOSE: To compare oncological, functional, and surgical outcomes of a large cohort of patients who underwent open retropubic radical prostatectomy (ORP) or robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Data from 18,805 RPs performed with either the open or the robot-assisted approaches at a single tertiary referral center between 2008 and 2022 were analyzed. The impact of surgical approach on biochemical recurrence-free survival, salvage radiotherapy-free survival, and metastasis-free survival was analyzed by log-rank test and Kaplan-Meier analysis in a propensity score (PS)-based matched cohort. Intraoperative and postoperative surgical outcomes were assessed. One-week, 3-month, and 12-month continence rates and 12-month erectile function (EF) were analyzed. RESULTS: No statistically significant differences in oncological outcomes were found between ORP and RARP. A slight statistically significant difference in favor of RARP was noted in urinary continence at 3 months (RARP vs. ORP: 81% vs. 77%, p = 0.007) and 12 months (91% vs. 89.3%, p = 0.008), respectively. The rate of EF was statistically significantly higher (60%) after RARP than after ORP (45%, p < 0.001). CONCLUSION: Both RARP and ORP yielded similar oncological outcomes. RARP offered a slight advantage in terms of continence recovery, but its clinical significance may be less meaningful. RARP resulted in significantly improved postoperative EF, suggesting a potential influence of both surgical experience and minimally invasive approach.

Comparative analysis of robot-assisted and open approach for PSMA-radioguided surgery in recurrent prostate cancer.

PURPOSE: To compare the oncological and surgical outcomes of patients with recurrent prostate cancer (PCa) who underwent either open or newly established robot-assisted salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS). MATERIALS AND METHODS: Patients who consecutively underwent PSMA-RGS for PCa recurrence between January 2021 and December 2022 were identified. The rate of complete biochemical response, biochemical recurrence-free survival [BFS], and the rate of salvage therapy were evaluated. Univariable and multivariable regression models tested the association between the surgical approach and surgical outcomes. RESULTS: Overall, 85 patients were selected, with 61 patients (72%) undergoing open PSMA-RGS and 24 patients (28%) receiving a robot-assisted approach. The oncological outcomes of the two groups were comparable (12-month BFS: 41% (Confidence interval (CI): 29-58%) vs. 39% (CI: 19-79%), p = 0.9, respectively). According to multivariable regression models, the robotic approach did not significantly influence estimated blood loss (EBL) (ß = -40, 95% CI: -103, 22; p = 0.2) and significantly increased operative time (OT) (ß = 28, 95% CI: 10, 46; p = 0.002). No Clavien-Dindo III-V complications were reported in the robotic group. CONCLUSION: Both, the open as well as the robot-assisted approach for PSMA-RGS had comparable oncological outcomes. No safety concerns arose for the robotic-assisted approach offering a potentially improved quality of life for patients.

Histopathological results of radical prostatectomy specimen of men younger than 50 years of age at the time of surgery: possible implications for prostate cancer screening programs?

INTRODUCTION: Prostate cancer (PCa) detection is usually achieved by PSA measurement and, if indicated, further diagnostics. The recent EAU guidelines recommend a first PSA test at the age of 50 years, if no family history of PCa or BRCA2 mutation exists. However, some men might harbor significant PCa at younger age; thus we evaluated the histopathological results of men treated with radical prostatectomy (RP) in their 40 s at our institution. MATERIALS AND METHODS: We relied on the data of all patients who underwent RP in our institution between 1992 and 2020 and were younger than 50 years at the time of surgery. The histopathological results are descriptively presented. Moreover, we tested the effect of a positive family history on the descriptive results. RESULTS: Overall, 1225 patients younger than 50 years underwent RP at our institution. Median age was 47 years. Most patients showed favorable histopathological characteristics. However, 20% of patients had extraprostatic disease (≥ pT3a), 15% had ISUP Gleason grade group ≥ 3, and 7% had positive lymph nodes (pN1). Patients with a known positive family history did not have a higher rate of adverse disease as their counterparts with a negative family history. DISCUSSION: Our data show that the majority of patients who were diagnosed with PCa at a very young age had favorable histopathological RP characteristics. However, a non-negligible proportion of patients already showed locally advanced disease and would have probably benefited from earlier PCa detection. This should be kept in mind when PCa screening recommendations are proposed.

Safety and efficiency of repeat salvage lymph node dissection for recurrence of prostate cancer using PSMA-radioguided surgery (RGS) after prior salvage lymph node dissection with or without initial RGS support.

BACKGROUND AND OBJECTIVE: Metastasis-directed therapy is a feasible option for low PSA, recurrent locoregional metastatic prostate cancer. After initial salvage surgery, patients with good response might consider a repeat salvage surgery in case of recurrent, isolated, and PSMA-positive metastases. This analysis aimed to evaluate the oncological outcome and safety of repeat PSMA-targeted radioguided surgery (RGS) after either prior RGS or "standard" salvage lymph node dissection (SLND). MATERIALS AND METHODS: We identified 37 patients undergoing repeat RGS after prior SLND (n = 21) (SLND-RGS) or prior RGS (n = 16) (RGS-RGS) between 2014 and 2021 after initial radical prostatectomy with or without pelvic radiation therapy at two German tertiary referral centers. Kaplan-Meier analyses and uni-/multivariable Cox regression models were used to investigate factors associated with biochemical recurrence-free survival (BRFS) and treatment-free survival (TFS) after repeat salvage surgery. RESULTS AND LIMITATIONS: Complete Biochemical Response (cBR, PSA < 0.2 ng/ml) was observed in 20/32 patients (5 NA). Median overall BRFS [95% confidence interval (CI)] after repeat salvage surgery was 10.8 months (mo) (5.3-22). On multivariable regression, only age (HR 1.09, 95% CI 1.01-1.17) and preoperative PSA (HR 1.23, 95% CI 1.01-1.50) were associated with shorter BRFS, although PSA (HR 1.16, 95% CI 0.99-1.36) did not achieve significant predictor status in univariable analysis before (p value = 0.07). Overall, one year after second salvage surgery, 89% of the patients (number at risk: 19) did not receive additional treatment and median TFS was not reached. Clavien-Dindo grade > 3a complications were observed in 8% (3/37 patients). Limitations are the retrospective evaluation, heterogeneous SLND procedures, lack of long-term follow-up data, and small cohort size. CONCLUSION: In this study, repeat RGS was safe and provided clinically meaningful biochemical recurrence- and treatment-free intervals for selected cases. Patients having low preoperative PSA seemed to benefit most of repeat RGS, irrespective of prior SLND or RGS or the time from initial RP/first salvage surgery.

Impact of positive surgical margin length and Gleason grade at the margin on oncologic outcomes in patients with nonorgan-confined prostate cancer.

PURPOSE: Positive surgical margins (PSM) represent a poor prognostic factor at radical prostatectomy (RP). To investigate the impact of PSM, its length, the focality and the Gleason grade at the PSM, on the oncologic outcomes in nonorgan-confined RP patients. METHODS: Within a high-volume center database, we identified patients who harbored non-organ-confined (pT3) prostate cancer (PCa) at RP between 2010 and 2016. Only patients without lymph node invasion were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of PSM on biochemical recurrence (BCR), metastasis, and cancer-specific death after RP in patients without adjuvant radiotherapy. RESULTS: Overall, 3705 patients were identified. Of those, 27.2% (n = 1007) harbored PSM. At 96 months after RP, BCR-free, metastasis-free and cancer-specific survival was 41.6 versus 57.5%, 82.7 versus 88.6%, and 94.7 versus 98.5% for patients with versus without PSM (all p < 0.001). BCR-free, metastasis-free and cancer-specific survival rates at 96 months were 56.7 versus 26.5% (p < 0.001), 94.4 versus 67.4% (p < 0.001), and 100.0 versus 87.1% (p < 0.01) for Gleason pattern 3 versus ≥ 4 at the margin and 45.0 versus 27.8% (p < 0.01), 83.3 versus 82.3% (p = 0.2), and 95.2 versus 92.7% (p = 0.3) for <4 mm versus ≥4 mm length of margin. In multivariable Cox models PSM was an independent predictor for BCR (hazard ratio [HR]:1.53, p < 0.001) and cancer-specific death (HR:2.75, p = 0.02). In subgroups of patients with PSM only, Gleason ≥ 4 at the margin (HR:1.60, p < 0.01) and length of PSM (HR:1.02, p < 0.05) was an independent predictor of BCR. CONCLUSION: PSM represents an independent predictor for worse oncologic outcome in nonorgan-confined PCa at RP. Gleason ≥ 4 at the margin was associated with the development of BCR, metastasis, and with cancer-specific death after RP. Next to margin status, Gleason at the margin and its length carry important information that should be reported for the specimen.

Optimizing Combined Magnetic Resonance Imaging (MRI)-Targeted and Systematic Biopsy Strategies: Sparing the Multiparametric MRI-Negative Transitional Zone in Presence of Exclusively Peripheral Multiparametric MRI-Suspect Lesions.

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.

Precision-guidance vs Systematic Sampling: Optimizing Biopsy Assessment of Secondary Prostate Cancer Suspicious Multiparametric Magnetic Resonance Imaging Lesions.

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.

Pan-segmental intraprostatic lesions involving mid-gland and apex of prostate (mid-apical lesions): assessing the true value of extreme apical biopsy cores.

OBJECTIVE: When considering increased morbidity of apical biopsies, the added diagnostic value of separate targeting of mid-gland and apical segment of the pan-segmental mid-apical mpMRI prostate cancer (PCa) suspicious lesions was assessed. MATERIALS AND METHODS: A total of 420 patients with a single mpMRI PCa-suspicious PI-RADS ≥ 3 intraprostatic lesion extending from the mid-gland to the apical segment of the gland underwent transrectal MRI-targeted (TBx) and systematic prostate biopsy. Clinically significant PCa (CsPCa) was defined as Gleason Score (GS) ≥ 3 + 4. PCa detection rates of TBx cores were assessed according to targeted anatomical segments. Finally, the diagnostic values of two theoretical TBx protocols utilizing 1-core (A) vs. 2-cores (B) per anatomical segment were compared. RESULTS: TBx within the pan-segmental mid-apical lesions yielded 44% of csPCa. After stratification into mid- vs. apical segment of the lesion, csPCa was detected in 36% (mid-gland) and 32% (apex), respectively. Within the patients who had no csPCa detection by mid-gland sampling (64%, n = 270), extreme apical TBx yielded additional 8.1% of csPCa. Comparison of extreme apical TBx strategy B vs. overall PCa detection in our cohort revealed corresponding similar rates of 49 vs.50% and 31 vs.32%, respectively. CONCLUSION: Separate analyses of both segments, mid-gland and apex, clearly revealed the diagnostic contribution of apical TBx. Our findings strongly suggest to perform extreme apical TBx even within pan-segmental lesions. Moreover, our results indicate that a higher number of cores sampled from the mid-gland segment might be avoided if complemented with a two-core extreme apical TBx.

Suitability of conventional systematic vs. MRI-guided targeted biopsy approaches to assess surgical treatment delay for radical prostatectomy.

OBJECTIVES: To assess if systematic (SBx) vs. transrectal or transperineal mpMRI-ultrasound targeted combined with systematic (TBx + SBx) biopsy confer different effects on treatment delay to radical prostatectomy measured as Gleason grade group (GGG) upgrade of prostate cancer (PCa). MATERIALS AND METHODS: We relied on a multi-institutional cohort of localized PCa patients who underwent RP in Martini-Klinik, Hamburg, or Prostate Center Northwest, Gronau, between 2014 and 2022. Analyses were restricted to PCa GGG 1-3 diagnosed at SBx (n = 4475) or TBx + SBx (n = 1282). Multivariable logistic regression modeling (MVA) predicting RP GGG upgrade of ≥ 1 was performed separately for SBx and TBx + SBx. RESULTS: Treatment delay to RP of < 90, 90-180 and 180-365 days was reported in 59%, 35% and 6.2% of SBx and in 60%, 34% and 5.9% of the TBx + SBx patients, respectively. Upgrade to GGG ≥ 4 at RP was detected in 15% of SBx patients and 0.86% of TBx patients. In MVA performed for SBx, treatment delay yielded independent predictor status (OR 1.17 95% CI 1.02-1.39, p = 0.028), whereas for TBx + SBx MVA, statistical significance was not achieved. CONCLUSION: Treatment delay remained independently associated with radical prostatectomy GGG upgrade after adjustment for clinical variables in the patients diagnosed with SBx alone, but not in those who received combined TBx + SBx. These findings can be explained through inherent misclassification rates of SBx, potentially obfuscating historical observations of natural PCa progression and potential dangers of treatment delay. Thus, mpMRI-guided combined TBx + SBx appears mandatory for prospective delay-based examinations of PCa.

Twenty-year trends in prostate cancer stage and grade migration in a large contemporary german radical prostatectomy cohort.

BACKGROUND: A trend towards inverse stage migration in prostate cancer (PCa) was reported. However, previous analyses did not take into account potential differences in sampling strategies (number of biopsy cores), which might have confounded these reports. MATERIAL AND METHODS: Within our single-institutional database we identified PCa patients treated with radical prostatectomy (RP) between 2000 and 2020 (n = 21,646). We calculated the estimated annual percentage change (EAPC) for D'Amico risk groups, biopsy Gleason Grade Group (GGG), PSA and cT stage as well as postoperative RP GGG and pT stage relying on log linear regression methodology. Subsequently, we repeated the analyses after adjustment for number of cores obtained at biopsy. RESULTS: Absolute rates of D'Amico low risk decreased (-30.1%), while intermediate and high risk increased (+21.2% and +9.0%, respectively). Rates of GGG I decreased (-50.0%), while GGG II-V increased, with the largest increase in GGG II (+22.5%). This trend, albeit less pronounced, was also recorded after adjusted EAPC analyses (p < .05). Specifically, EAPC values for D'Amico low vs intermediate vs high risk were -1.07%, +0.37%, +0.45%, respectively, and EAPC values for GGG ranged between -0.71% (GGG I) and +0.80% (GGG IV). Finally, an increase in ≥cT2 (EAPC: +3.16%) was displayed (all p < .001). These trends were confirmed in EAPC calculations in RP GGG and pT stages (p < .001). CONCLUSION: Our findings confirm the trend towards less frequent treatment of low risk PCa and more frequent treatment of high risk PCa, also after adjustment for number of biopsy cores.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. METHODS: In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. RESULTS: A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). CONCLUSIONS: The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .).

Regional Lymph Node Metastasis on Prostate Specific Membrane Antigen Positron Emission Tomography Correlates with Decreased Biochemical Recurrence-Free and Therapy-Free Survival after Radical Prostatectomy: A Retrospective Single-Center Single-Arm Observational Study.

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 68Ga-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.

Combined systematic versus stand-alone multiparametric MRI-guided targeted fusion biopsy: nomogram prediction of non-organ-confined prostate cancer.

OBJECTIVE: Based on unfavorable oncological and functional outcomes of non-organ-confined (NOC) prostate cancer (PCa), defined as ≥ pT3, pN1 or both, we aimed to develop a NOC prediction tool based on multiparametric MRI-guided targeted fusion biopsy (TBx). MATERIALS AND METHODS: Analyses were restricted to 594 patients with simultaneous PCa detection at systematic biopsy (SBx), TBx and subsequent radical prostatectomy (RP) at our institution. Development (n = 396; cohort 1) and validation cohorts (n = 198; cohort 2) were used to develop and validate the NOC nomogram. A head-to-head comparison was performed between stand-alone TBx model and combined TBx/SBx model. Second validation was performed in patients with positive TBx, but negative SBx (n = 193; cohort 3). RESULTS: The most parsimonious TBx model included three independent predictors of NOC: pretreatment PSA (OR 1.05 95% CI: 1.01-1.08), highest TBx-detected Gleason pattern (3 + 3 [REF] vs. ≥ 4 + 5; OR 9.3 95% CI 3.8-22) and presence of TBx-detected perineural invasion (OR 2.2 95% CI: 1.3-3.6). The combined TBx/SBx model had the same predictors. For the stand-alone TBx and combined TBx/SBx model, external validation yielded accuracy of 76.5% (95% CI: 69.3-83.1) and 76.6% (95% CI: 69.4-83.6) within cohort 2. The external validation of the stand-alone TBx model yielded 72.4% (95% CI: 65.0-79.6) accuracy within cohort 3. CONCLUSION: Our stand-alone TBx-based nomogram can identify PCa patients at the risk of NOC, using three simple variables, with the similar accuracy as the TBx/SBx-based model. It is non-inferior to combined TBx/SBx-based model and performs with sufficient accuracy in specific patients with positive TBx, but negative SBx.

Minimum Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy Cores Needed for Prostate Cancer Detection: Multivariable Retrospective, Lesion Based Analyses of Patients Treated with Radical Prostatectomy.

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.

Automated multiparametric localization of prostate cancer based on B-mode, shear-wave elastography, and contrast-enhanced ultrasound radiomics.

OBJECTIVES: The aim of this study was to assess the potential of machine learning based on B-mode, shear-wave elastography (SWE), and dynamic contrast-enhanced ultrasound (DCE-US) radiomics for the localization of prostate cancer (PCa) lesions using transrectal ultrasound. METHODS: This study was approved by the institutional review board and comprised 50 men with biopsy-confirmed PCa that were referred for radical prostatectomy. Prior to surgery, patients received transrectal ultrasound (TRUS), SWE, and DCE-US for three imaging planes. The images were automatically segmented and registered. First, model-based features related to contrast perfusion and dispersion were extracted from the DCE-US videos. Subsequently, radiomics were retrieved from all modalities. Machine learning was applied through a random forest classification algorithm, using the co-registered histopathology from the radical prostatectomy specimens as a reference to draw benign and malignant regions of interest. To avoid overfitting, the performance of the multiparametric classifier was assessed through leave-one-patient-out cross-validation. RESULTS: The multiparametric classifier reached a region-wise area under the receiver operating characteristics curve (ROC-AUC) of 0.75 and 0.90 for PCa and Gleason > 3 + 4 significant PCa, respectively, thereby outperforming the best-performing single parameter (i.e., contrast velocity) yielding ROC-AUCs of 0.69 and 0.76, respectively. Machine learning revealed that combinations between perfusion-, dispersion-, and elasticity-related features were favored. CONCLUSIONS: In this paper, technical feasibility of multiparametric machine learning to improve upon single US modalities for the localization of PCa has been demonstrated. Extended datasets for training and testing may establish the clinical value of automatic multiparametric US classification in the early diagnosis of PCa. KEY POINTS: • Combination of B-mode ultrasound, shear-wave elastography, and contrast ultrasound radiomics through machine learning is technically feasible. • Multiparametric ultrasound demonstrated a higher prostate cancer localization ability than single ultrasound modalities. • Computer-aided multiparametric ultrasound could help clinicians in biopsy targeting.

A comparative study of robot-assisted and open radical prostatectomy in 10 790 men treated by highly trained surgeons for both procedures.

OBJECTIVE: To compare oncological, functional and surgical outcomes of open retropubic radical prostatectomy (ORP) vs robot-assisted laparoscopic radical prostatectomy (RARP). PATIENTS AND METHODS: We identified 10 790 consecutive treated patients within our prospective database (2008-2016) who underwent either ORP (7007 patients) or RARP (3783). All procedures were performed by seven highly trained surgeons performing both surgical approaches regularly. Oncological (48-month biochemical recurrence [BCR] rate), functional (urinary continence, erectile function), and surgical outcomes (rate of nerve-sparing [NS] procedures, lymph node yield, surgical margin [SM] status, length of hospital stay [LOS], operation time, blood loss, transfusion rate, time to catheter removal) were assessed. Kaplan-Meier, multivariable Cox and logistic regression models were used to test for BCR and functional outcome differences. RESULTS: No statistically significant difference regarding oncological outcome distinguished between ORP vs RARP. For functional outcomes, the 1-week continence rates were higher in the ORP group (25.8% vs 21.8%, P < 0.001). At 3 months, no statistically significant differences were observed. At 12 months, continence rates were modestly higher in the RARP group (90.3% vs 88.8%, P = 0.01). This effect was no longer observed after stratification for age-groups. The 12-month potency rates were similar in ORP vs RARP (80.3% vs 83.6%, P = 0.33). For surgical outcomes, there was no significant difference in the rates of NS procedures, lymph node yield, SM status, and LOS. Conversely, operation time was shorter in ORP, and blood loss, transfusion rates and time to catheter removal were significantly lower in RARP. CONCLUSIONS: Both surgical approaches, performed in a high-volume centre by the same surgeons, achieve excellent, comparable oncological and functional outcomes. However, a modest advantage for RARP for surgical outcomes was observed, most likely attributable to its minimally invasive nature, and better teaching capabilities. Consequently, more than the surgical approach itself, the well-trained surgeon remains the most important factor to achieve satisfactory outcomes.

Inverse stage migration patterns in North American patients undergoing local prostate cancer treatment: a contemporary population-based update in light of the 2012 USPSTF recommendations.

PURPOSE: Recent studies demonstrated ongoing inverse stage migration in prostate cancer (PCa) patients towards more advanced and unfavorable tumors. The USPSTF grade D recommendation may impact this trend in North American patients. We assessed contemporary stage migration and treatment trends in a large North American cohort diagnosed with PCa 2009-2014. METHODS: Time-trend analyses were performed in patients within the Surveillance, Epidemiology, and End Results database, with complete data of clinical tumor stage, biopsy Gleason score, and validated PSA values, resulting in 211,645 assessable patients. Patients were stratified according to their different treatment methods [radical prostatectomy (RP), radiotherapy (RT), and no local treatment (NLT)] and according to clinical and pathological risk stratification (D'Amico and CAPRA-S score). RESULTS: Over time, proportions of D'Amico low-risk (LR) decreased, with an increase in intermediate-to-high-risk (IR/HR) patients. These trends were more distinct in men ≥ 70 years. NLT proportions increased, most notably in D'Amico LR and/or older patients. Conversely, RP proportions remained stable in younger HR and increased in older HR patients. Similar patterns were demonstrated in the RP-treated subgroup: D'Amico HR, pT3, and/or lymph-node invasion or CAPRA-S HR proportions increased from 23.5 to 30.8, 24.3 to 32.9, and 10.7 to 16.3% (each p ≤ 0.015). CONCLUSIONS: Inverse stage migration with increase of unfavorable PCa continues in most contemporary North American patients. However, a paradigm shift to treat LR patients with less invasive methods (NLT) was demonstrated. Contrary, HR patients increasingly undergo LT. Future studies with long-term follow-up might answer if inverse stage migration vs. treatment trends translate into different PCa metastases/mortality rates vs. proposed NLT benefits, particularly related to USPSTF-recommended reduced PSA screening.