Multidisciplinary real-world management of metastatic castration-sensitive prostate cancer: a French national study (PROFILE study).

While androgen deprivation therapy (ADT) has been the standard of care for patients with metastatic castration-sensitive prostate cancer (mCSPC), recent strategies like intensification of systemic treatment [12] (i.e. adding another treatment to ADT) and radiotherapy have improved overall survival. PROFILE, a national retrospective multicentric real world study, involved patients with mCSPC recruited by medical oncologists, urologists, and radiation oncologists, and who started treatment between November 2020 and May 2021. Patients by sites were included consecutively. Data were collected from medical records. Primary objectives were to:(1)describe retrospectively the characteristics of whole population of patients with mCSPC as well as subgroups defined by prognostic factors in France at diagnosis; (2) identify current practices for managing mCSPC in a real-life clinical setting. Among the 416 patients with mCSPC included in the PROFILE study, 315 (76%) were synchronous (metastasis at the initial diagnosis) and 101 (24%) were metachronous patients (metastasis diagnosed post-progression). A majority (83% of synchronous and 73% of metachronous patients) received an intensified systemic treatment (ADT plus ARSI [androgen-receptor signaling inhibitors] ± chemotherapy ± primary tumour radiotherapy ± metastasis-directed therapy (MDT)), while only 40% of low-volume patients received prostate radiotherapy. This study depicts the standardization of new therapeutic strategies for patients with mCSPC in France with most of them receiving an intensified treatment, mainly with ADT + ARSI (64% of synchronous intensified patients and 76% of metachronous intensified patients). Most of patients were assessed using conventional imaging (CT scan and/or bone scan). Overall, PROFILE results are in line with French and European guidelines for diagnosis, management, and follow-up of such patients. [12,13].

Circulating Biomarkers Predictive of Treatment Response in Patients with Hormone-sensitive or Castration-resistant Metastatic Prostate Cancer: A Systematic Review.

BACKGROUND AND OBJECTIVE: Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa. METHODS: We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level. KEY FINDINGS AND LIMITATIONS: The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to 177Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB). CONCLUSIONS AND CLINICAL IMPLICATIONS: BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies. PATIENT SUMMARY: We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.

PARP inhibitors in prostate cancers, is it time for combinations?

Despite several improvements in outcomes, metastatic prostate cancer remains deadly. Alterations in the homologous recombination repair (HRR) pathway are associated with more aggressive disease. Olaparib and rucaparib, two poly-ADP-ribose polymerase (PARP) inhibitors, have received approval from the authorities of several countries for their anti-tumoral effects in patients with metastatic castration-resistant prostate cancers harboring HRR gene alterations, in particular BRCA2. More recently, it has been hypothesized that new hormonal therapies (NHTs) and PARP inhibitors (PARPi) could have synergistic actions and act independently of HRR deficiency. This review proposes to discuss the advantages and disadvantages of PARPi used as monotherapy or in combination with NHTs and whether there is a need for molecular selection.

The impact of prostate volume estimation on the risk-adapted biopsy decision based on prostate-specific antigen density and magnetic resonance imaging score.

PURPOSE: Utility of prostate-specific antigen density (PSAd) for risk-stratification to avoid unnecessary biopsy remains unclear due to the lack of standardization of prostate volume estimation. We evaluated the impact of ellipsoidal formula using multiparametric magnetic resonance (MRI) and semi-automated segmentation using tridimensional ultrasound (3D-US) on prostate volume and PSAd estimations as well as the distribution of patients in a risk-adapted table of clinically significant prostate cancer (csPCa). METHODS: In a prospectively maintained database of 4841 patients who underwent MRI-targeted and systematic biopsies, 971 met inclusions criteria. Correlation of volume estimation was assessed by Kendall's correlation coefficient and graphically represented by scatter and Bland-Altman plots. Distribution of csPCa was presented using the Schoots risk-adapted table based on PSAd and PI-RADS score. The model was evaluated using discrimination, calibration plots and decision curve analysis (DCA). RESULTS: Median prostate volume estimation using 3D-US was higher compared to MRI (49cc[IQR 37-68] vs 47cc[IQR 35-66], p < 0.001). Significant correlation between imaging modalities was observed (τ = 0.73[CI 0.7-0.75], p < 0.001). Bland-Altman plot emphasizes the differences in prostate volume estimation. Using the Schoots risk-adapted table, a high risk of csPCa was observed in PI-RADS 2 combined with high PSAd, and in all PI-RADS 4-5. The risk of csPCa was proportional to the PSAd for PI-RADS 3 patients. Good accuracy (AUC of 0.69 and 0.68 using 3D-US and MRI, respectively), adequate calibration and a higher net benefit when using 3D-US for probability thresholds above 25% on DCA. CONCLUSIONS: Prostate volume estimation with semi-automated segmentation using 3D-US should be preferred to the ellipsoidal formula (MRI) when evaluating PSAd and the risk of csPCa.

Outcomes after radical nephrectomy with vena cava thrombectomy using multidisciplinary approach: a single center experience.

INTRODUCTION: To describe the perioperative outcomes in patients treated with radical nephrectomy with cava thrombectomy at all thrombi levels using a multidisciplinary approach, with or without extracorporeal circulation (ECC), and to identify factors associated with perioperative morbidity. METHODS: We retrospectively identified 42 patients who were diagnosed with renal cell carcinoma (RCC) and a vena cava thrombus and treated with radical nephrectomy and cava thrombectomy by a double surgical team at Lyon University Hospital from 2008 through 2021. The surgeons operated in the cardiothoracic operating theater to proceed with median sternotomy or ECC, if necessary. The primary endpoint of this study was perioperative morbidity and mortality assessed using the Clavien-Dindo scale. Complications were recorded until 90 days after surgery, and those classified as grade IIIa or higher were considered high-grade complications. RESULTS: Overall, 32 (76%) patients required ECC. No intraoperative mortality occurred; however, two patients (5%) died within 30 days. Complications occurred within 30 days in 30 patients (72%), with severe complications observed in 10 patients (24%). No further complications occurred between 30 and 90 days. Multivariate analysis revealed that age, thrombus level, ECC, American Society of Anesthesiologists physical status, symptoms, and metastasis at presentation were not significantly associated with high-grade complications (p>0.05). CONCLUSIONS: Multidisciplinary approach is essential and frequent use of ECC, when achieved by a trained team, may facilitate surgery, and is associated with low perioperative morbidity, especially for patients with high-level thrombi.

Preparing for the Worst: Management and Predictive Factors of Open Conversion During Minimally Invasive Renal Tumor Surgery (UroCCR-135 Study).

Background and objective: Data regarding open conversion (OC) during minimally invasive surgery (MIS) for renal tumors are reported from big databases, without precise description of the reason and management of OC. The objective of this study was to describe the rate, reasons, and perioperative outcomes of OC in a cohort of patients who underwent MIS for renal tumor initially. The secondary objective was to find the factors associated with OC. Methods: Between 2008 and 2022, of the 8566 patients included in the UroCCR project prospective database (NCT03293563), who underwent laparoscopic or robot-assisted minimally invasive partial (MIPN) or radical (MIRN) nephrectomy, 163 experienced OC. Each center was contacted to enlighten the context of OC: "emergency OC" implied an immediate life-threatening situation not reasonably manageable with MIS, otherwise "elective OC". To evaluate the predictive factors of OC, a 2:1 paired cohort on the UroCCR database was used. Key findings and limitations: The incidence rate of OC was 1.9% for all cases of MIS, 2.9% for MIRN, and 1.4% for MIPN. OC procedures were mostly elective (82.2%). The main reason for OC was a failure to progress due to anatomical difficulties (42.9%). Five patients (3.1%) died within 90 d after surgery. Increased body mass index (BMI; odds ratio [OR]: 1.05, 95% confidence interval [CI]: 1.01-1.09, p = 0.009) and cT stage (OR: 2.22, 95% CI: 1.24-4.25, p = 0.008) were independent predictive factors of OC. Conclusions and clinical implications: In MIS for renal tumors, OC was a rare event (1.9%), caused by various situations, leading to impaired perioperative outcomes. Emergency OC occurred once every 300 procedures. Increased BMI and cT stage were independent predictive factors of OC. Patient summary: The incidence rate of open conversion (OC) in minimally invasive surgery for renal tumors is low. Only 20% of OC procedures occur in case of emergency, and others are caused by various situations. Increased body mass index and cT stage were independent predictive factors of OC.

Predicting contralateral extraprostatic extension in unilateral high-risk prostate cancer: a multicentric external validation study.

PURPOSE: Accurate prediction of extraprostatic extension (EPE) is crucial for decision-making in radical prostatectomy (RP), especially in nerve-sparing strategies. Martini et al. introduced a three-tier algorithm for predicting contralateral EPE in unilateral high-risk prostate cancer (PCa). The aim of the study is to externally validate this model in a multicentric European cohort of patients. METHODS: The data from 208 unilateral high-risk PCa patients diagnosed through magnetic resonance imaging (MRI)-targeted and systematic biopsies, treated with RP between January 2016 and November 2021 at eight referral centers were collected. The evaluation of model performance involved measures such as discrimination (AUC), calibration, and decision-curve analysis (DCA) following TRIPOD guidelines. In addition, a comparison was made with two established multivariable logistic regression models predicting the risk of side specific EPE for assessment purposes. RESULTS: Overall, 38%, 48%, and 14% of patients were categorized as low, intermediate, and high-risk groups according to Martini et al.'s model, respectively. At final pathology, EPE on the contralateral prostatic lobe occurred in 6.3%, 12%, and 34% of patients in the respective risk groups. The algorithm demonstrated acceptable discrimination (AUC 0.68), comparable to other multivariable logistic regression models (p = 0.3), adequate calibration and the highest net benefit in DCA. The limitations include the modest sample size, retrospective design, and lack of central revision. CONCLUSION: Our findings endorse the algorithm's commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients.

Transperineal or Transrectal Magnetic Resonance Imaging-targeted Biopsy for Prostate Cancer Detection.

BACKGROUND AND OBJECTIVE: A notable paradigm shift has emerged in the choice of prostate biopsy approach, with a transition from transrectal biopsy (TRBx) to transperineal biopsy (TPBx) driven by the lower risk of severe urinary tract infections. The impact of this change on detection of clinically significant prostate cancer (csPCa) remains a subject of debate. Our aim was to compare the csPCa detection rate of TRBx and TPBx. METHODS: Patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for clinically localized PCa at 15 European referral centers from 2016 to 2023 were included. A propensity score matching (PSM) analysis was performed to minimize selection biases. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). KEY FINDINGS AND LIMITATIONS: Of 3949 patients who met the study criteria, 2187 underwent TRBx and 1762 underwent TPBx. PSM resulted in 1301 matched pairs for analysis. Patient demographics and tumor characteristics were comparable in the matched cohorts. TPBx versus TRBx was associated with greater detection of csPCa, whether defined as International Society of Urological Pathology grade group ≥2 (51% vs 45%; OR 1.37, 95% CI 1.15-1.63; p = 0.001) or grade group ≥3 (29% vs 23%; OR 1.38, 95% CI 1.13-1.67; p = 0.001). Similar results were found when considering MRI-targeted biopsy alone and after stratifying patients according to tumor location, Prostate Imaging-Reporting and Data System score, and clinical features. Limitations include the retrospective nature of the study and the absence of centralized MRI review. CONCLUSIONS: Our findings bolster existing understanding of the additional advantages offered by TPBx. Further randomized trials to fully validate these findings are awaited. PATIENT SUMMARY: We compared the rate of detection of clinically significant prostate cancer with magnetic resonance imaging (MRI)-guided biopsies in which the sample needle is passed through the perineum or the rectum. Our results suggest that the perineal approach is associated with better detection of aggressive prostate cancer.

Does Overgrading on Targeted Biopsy of Magnetic Resonance Imaging-visible Lesions in Prostate Cancer Lead to Overtreatment?

BACKGROUND AND OBJECTIVE: Targeted biopsy of the index prostate cancer (PCa) lesion on multiparametric magnetic resonance imaging (MRI) is effective in reducing the risk of overdiagnosis of indolent PCa. However, it remains to be determined whether MRI-targeted biopsy can lead to a stage shift via overgrading of the index lesion by focusing only on the highest-grade component, and to a subsequent risk of overtreatment. Our aim was to assess whether overgrading on MRI-targeted biopsy may lead to overtreatment, using radical prostatectomy (RP) specimens as the reference standard. METHODS: Patients with clinically localized PCa who had positive MRI findings (Prostate Imaging-Reporting and Data System [PI-RADS] score ≥3) and Gleason grade group (GG) ≥2 disease detected on MRI-targeted biopsy were retrospectively identified from a prospectively maintained database that records all RP procedures from eight referral centers. Biopsy grade was defined as the highest grade detected. Downgrading was defined as lower GG for the RP specimen than for MRI-targeted biopsy. Overtreatment was defined as downgrading to RP GG 1 for cases with GG ≥2 on biopsy, or to RP low-burden GG 2 for cases with GG ≥3 on biopsy. KEY FINDINGS AND LIMITATIONS: We included 1020 consecutive biopsy-naïve patients with GG ≥2 PCa on MRI-targeted biopsy in the study. Pathological analysis of RP specimens showed downgrading in 178 patients (17%). The transperineal biopsy route was significantly associated with a lower risk of downgrading (odds ratio 0.364, 95% confidence interval 0.142-0.814; p = 0.022). Among 555 patients with GG 2 on targeted biopsy, only 18 (3.2%) were downgraded to GG 1 on RP. Among 465 patients with GG ≥3 on targeted biopsy, three (0.6%) were downgraded to GG 1 and seven were downgraded to low-burden GG 2 on RP. The overall risk of overtreatment due to targeted biopsy was 2.7% (28/1020). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our multicenter study revealed no strong evidence that targeted biopsy results could lead to a high risk of overtreatment. PATIENT SUMMARY: In the diagnosis pathway for prostate cancer, results for targeted biopsies guided by magnetic resonance imaging (MRI) scans lead to a negligible proportion of overtreatment.

Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

BACKGROUND AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI. METHODS: The lesions targeted at biopsy in the MRI-FIRST dataset were retrospectively delineated and assessed using a previously developed algorithm. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score assigned prospectively before biopsy and the algorithm score calculated retrospectively in the regions of interest were compared for diagnosing GG ≥2 cancer, using the areas under the curve (AUCs), and sensitivities and specificities calculated with predefined thresholds (PIRADSv2 scores ≥3 and ≥4; algorithm scores yielding 90% sensitivity in the training database). Ten predefined biopsy strategies were assessed retrospectively. KEY FINDINGS AND LIMITATIONS: After excluding 19 patients, we analysed 232 patients imaged on 16 different scanners; 85 had GG ≥2 cancer at biopsy. At patient level, AUCs of the algorithm and PI-RADSv2 were 77% (95% confidence interval [CI]: 70-82) and 80% (CI: 74-85; p = 0.36), respectively. The algorithm's sensitivity and specificity were 86% (CI: 76-93) and 65% (CI: 54-73), respectively. PI-RADSv2 sensitivities and specificities were 95% (CI: 89-100) and 38% (CI: 26-47), and 89% (CI: 79-96) and 47% (CI: 35-57) for thresholds of ≥3 and ≥4, respectively. Using the PI-RADSv2 score to trigger a biopsy would have avoided 26-34% of biopsies while missing 5-11% of GG ≥2 cancers. Combining prostate-specific antigen density, the PI-RADSv2 and algorithm's scores would have avoided 44-47% of biopsies while missing 6-9% of GG ≥2 cancers. Limitations include the retrospective nature of the study and a lack of PI-RADS version 2.1 assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The algorithm provided robust results in the multicentre multiscanner MRI-FIRST database and could help select patients for biopsy. PATIENT SUMMARY: An artificial intelligence-based algorithm aimed at diagnosing aggressive cancers on prostate magnetic resonance imaging showed results similar to expert human assessment in a prospectively acquired multicentre test database.

Interest of the POSPOM score in estimating postoperative complication risk after radical cystectomy.

INTRODUCTION: Identifying patients at risk after cystectomy for cancer is essential. The POSPOM score is a non-specific urological surgery score for estimating postoperative hospital mortality. This study sought to validate the POSPOM score for predicting postoperative morbidity and mortality after cystectomy. METHODS: The study retrospectively included all patients undergoing cystectomy for muscle-invasive or locally advanced bladder cancer between 2010 and 2019 in one center. The primary objective was validation of the POSPOM score for calculating severe postoperative morbidity [Clavien-Dindo (CDC)≥3] and 90-day mortality after cystectomy. Secondary objectives were comparison to other predictive scores [Charlson (CCI), ASA]. RESULTS: At 90days, out of 167 patients, 26% (n=44) had a CDC≥3 complication and 8.4% (n=14) had died. POSPOM correlated with the risk of death at 90days (P<0.001) and postoperative transfusion (P<0.01). Patients with CDC≥3 complications had higher CCI and POSPOM (median 6.5 vs. 5, P<0.01 and 6.49% vs. 5.58%, P=0.029, respectively). Patients who died postoperatively had higher CCI and POSPOM (median 8 vs. 6, P<0.001 and 23.9% vs. 5.58%, P<0.001, respectively). The prognostic value of the POSPOM score for predicting mortality appears better [AUC=0.886 (0.798-0.973)] compared with CCI [AUC=0.812 (0.710-0.915)] and ASA [AUC=0.739 (0.630-0.849)], but not for predicting morbidity. CONCLUSION: This study confirms the robustness of the POSPOM score for estimating mortality and its limitations for predicting postoperative morbidity.

Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Biopsies for Prostate Cancer Diagnosis: Final Results of the Randomized PERFECT trial (CCAFU-PR1).

BACKGROUND: Recent guidelines favor transperineal (TP) prostate biopsies over the transrectal (TR) approach due to a reduced sepsis risk. Yet, evidence from controlled trial comparing both approaches within the MRI-targeted pathway for significant prostate cancer (PCa) detection is lacking. OBJECTIVE: To compare the significant PCa detection rate between magnetic resonance imaging (MRI)-targeted TR and TP approaches in biopsy-naïve patients. DESIGN, SETTING, AND PARTICIPANTS: In this noninferiority controlled trial, we randomized (ratio 1:1) 270 MRI-positive biopsy-naïve patients. INTERVENTION: MRI-targeted TP versus TR biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: The primary outcome was the detection rate of significant PCa (International Society of Urological Pathology [ISUP] ≥2) in MRI-targeted biopsies. Secondary outcomes were any-grade PCa detection, detection on concomitant systematic biopsy, complications, and functional outcomes. RESULTS AND LIMITATIONS: Targeted biopsies identified significant PCa in 47.2% of TP and 54.2% of TR participants (-7%, p = 0.6235). On a per-lesion analysis, posterior lesions yielded higher detection rates via TR (59.0% vs 44.3%, p = 0.0443), while anterior lesions were more frequently detected via TP (40.6% vs 26.5%, p = 0.2228). The overall (any grade) cancer detection rate in targeted biopsies was comparable between groups: 71.3% (TP) versus 64.1% (TR; p = 0.2209) with significantly more ISUP 1 cases detected in the TP arm. Adverse events of grade ≥2 were not different between TP (35.7%) and TR (40.5%, p = 0.4256). One TR patient (0.8%) experienced grade 3 sepsis. Quality of life, and urinary and sexual function, as well as pain scores, were comparable between groups. CONCLUSIONS: Despite a comparable overall detection rate for any-grade PCa, noninferiority of TP over TR for MRI-targeted biopsies for significant PCa detection was not demonstrated. However, MRI lesion location influenced biopsy route performance, suggesting that a pragmatic approach based on lesion location might enhance significant PCa assessment. PATIENT SUMMARY: This trial compared the efficacy and safety of two biopsy approaches for prostate cancer diagnosis. Both approaches seem complementary according to the lesion location.

The Added Value of Side-specific Systematic Biopsy in Patients Diagnosed by Magnetic Resonance Imaging-targeted Prostate Biopsy.

BACKGROUND: Systematic biopsy (SB) combined with magnetic resonance imaging (MRI)-targeted biopsy is still recommended considering the risk of missing clinically significant prostate cancer (csPCa). OBJECTIVE: To evaluate the added value in csPCa detection on side-specific SB relative to MRI lesion and to externally validate the Noujeim risk stratification model that predicts the risk of csPCa on distant SB cores relative to the index MRI lesion. DESIGN, SETTING, AND PARTICIPANTS: Overall, 4841 consecutive patients diagnosed by MRI-targeted biopsy and SB for Prostate Imaging Reporting and Data System score ≥3 lesions were identified from a prospectively maintained database between January 2016 and April 2023 at 15 European referral centers. A total of 2387 patients met the inclusion criteria and were included in the analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: McNemar's test was used to compare the csPCa detection rate between several biopsy strategies including MRI-targeted biopsy, side-specific SB, and a combination of both. Model performance was evaluated in terms of discrimination using area under the receiver operation characteristic curve (AUC), calibration plots, and decision curve analysis. Clinically significant prostate cancer was defined as International Society of Urological Pathology grade group ≥2. RESULTS AND LIMITATIONS: Overall, the csPCa detection rate was 49%. Considering MRI-targeted biopsy as reference, the added values in terms of csPCa detection were 5.8% (relative increase of 13%), 4.2% (relative increase of 9.8%), and 2.8% (relative increase of 6.1%) for SB, ipsilateral SB, and contralateral SB, respectively. Only 35 patients (1.5%) exclusively had csPCa on contralateral SB (p < 0.001). Considering patients with csPCa on MRI-targeted biopsy and ipsilateral SB, the upgrading rate was 2% (20/961) using contralateral SB (p < 0.001). The Noujeim model exhibited modest performance (AUC of 0.63) when tested using our validation set. CONCLUSIONS: The added value of contralateral SB was negligible in terms of cancer detection and upgrading rates. The Noujeim model could be included in the decision-making process regarding the appropriate prostate biopsy strategy. PATIENT SUMMARY: In the present study, we collected a set of patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for the detection of prostate cancer. We found that biopsies taken at the opposite side of the MRI suspicious lesion have a negligible impact on cancer detection. We also validate a risk stratification model that predicts the risk of cancer on biopsies beyond 10 mm from the initial lesion, which could be used in daily practice to improve the personalization of the prostate biopsy.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer: A Systematic Review (French ccAFU).

The aim of this study was to systematically review the current evidence regarding the oncological and functional outcomes of salvage radical prostatectomy (sRP) for recurrent prostate cancer. A systematic review was conducted throughout September 2022 using the PubMed, Science Direct, Scopus, and Embase databases. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. A total of 55 studies (3836 patients) met our eligibility criteria. The vast majority of men included had radiation therapy (including brachytherapy) as their first-line treatment (n = 3240, 84%). Other first-line treatments included HIFU (n = 338, 9%), electroporation (n = 59, 2%), proton beam therapy (n = 54, 1.5%), cryotherapy (n = 34, 1%), focal vascular targeted photodynamic therapy (n = 22, 0.6%), and transurethral ultrasound ablation (n = 19, 0.5%). Median preoperative PSA, at the time of recurrence, ranged from 1.5 to 14.4 ng/mL. The surgical approach was open in 2300 (60%) cases, robotic in 1465 (38%) cases, and laparoscopic in 71 (2%) cases. Since 2019, there has been a clear increase in robotic versus conventional surgery (1245 versus 525 cases, respectively). The median operative time and blood loss ranged from 80 to 297 min and 75 to 914 mL, respectively. Concomitant lymph node dissection was performed in 2587 cases (79%). The overall complication rate was 34%, with a majority of Clavien grade I or II complications. Clavien ≥ 3 complications ranged from 0 to 64%. Positive surgical margins were noted in 792 cases (32%). The median follow-up ranged from 4.6 to 94 months. Biochemical recurrence after sRP ranged from 8% to 51.5% at 12 months, from 0% to 66% at 22 months, and from 48% to 59% at 60 months. The specific and overall survival rates ranged from 13.4 to 98% and 62 to 100% at 5 years, respectively. Urinary continence was maintained in 52.1% of cases. sRP demonstrated acceptable oncological outcomes. These results, after sRP, are influenced by several factors, and above all by pre-treatment assessment, including imaging, with the development of mpMRI and metabolic imaging. Our results demonstrated that SRP can be considered a suitable treatment option for selected patients, but the level of evidence remains low.

MRI lesion size is more important than the number of positive biopsy cores in predicting adverse features and recurrence after radical prostatectomy: implications for active surveillance criteria in intermediate-risk patients.

INTRODUCTION: To determine associations between prostate cancer (PCa) tumor burden measured on biopsy or multiparametric magnetic resonance imaging (mpMRI) and outcomes in intermediate-risk (IR) International Society of Urological Pathology (ISUP) grade 2 men managed with primary radical prostatectomy (RP). METHODS: This retrospective, multicenter study was conducted in eight referral centers. The cohort included IR PCa patients who had ISUP 2 at biopsy. We defined biopsy tumor burden as low/high based on the absence/presence of more than 25% positive cores. Tumor burden on imaging was defined as low/high based on maximum lesion diameter, <15 mm and ≥15 mm at mpMRI, respectively. The histological endpoint of the study was adverse features at RP, defined as ≥pT3a stage and/or lymph node invasion and/or ISUP ≥3 at final pathology. The clinical endpoint was biochemical recurrence (BCR) after RP. RESULTS: A total of 698 IR patients was included, of whom 335 (48%) had adverse features. In multivariate logistic regression analysis, there was no statistical association between tumor burden at biopsy and adverse features (p = 0.7). Tumor size ≥15 mm at mpMRI was significantly associated with adverse pathology (OR 1.65, 95%CI 1.14-2.39; p = 0.01). No significant association was observed between tumor burden at biopsy and BCR (p = 0.4). Tumor size ≥15 mm at mpMRI was significantly associated with BCR (HR 1.96, 95% CI 1.01-3.80; p = 0.04). CONCLUSIONS: Our data support extending the inclusion criteria to ISUP 2 men with >25% positive cores, provided they have a low tumor size at mpMRI (<15 mm). Prospective studies should be performed to validate these findings.

A Novel Nomogram to Identify Candidates for Focal Therapy Among Patients with Localized Prostate Cancer Diagnosed via Magnetic Resonance Imaging-Targeted and Systematic Biopsies: A European Multicenter Study.

BACKGROUND: Suitable selection criteria for focal therapy (FT) are crucial to achieve success in localized prostate cancer (PCa). OBJECTIVE: To develop a multivariable model that better delineates eligibility for FT and reduces undertreatment by predicting unfavorable disease at radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: Data were retrospectively collected from a prospective European multicenter cohort of 767 patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies followed by RP in eight referral centers between 2016 and 2021. The Imperial College of London eligibility criteria for FT were applied: (1) unifocal MRI lesion with Prostate Imaging-Reporting and Data System score of 3-5; (2) prostate-specific antigen (PSA) ≤20 ng/ml; (3) cT2-3a stage on MRI; and (4) International Society of Urological Pathology grade group (GG) 1 and ≥6 mm or GG 2-3. A total of 334 patients were included in the final analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was unfavorable disease at RP, defined as GG ≥4, and/or lymph node invasion, and/or seminal vesicle invasion, and/or contralateral clinically significant PCa. Logistic regression was used to assess predictors of unfavorable disease. The performance of the models including clinical, MRI, and biopsy information was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis. A coefficient-based nomogram was developed and internally validated. RESULTS AND LIMITATIONS: Overall, 43 patients (13%) had unfavorable disease on RP pathology. The model including PSA, clinical stage on digital rectal examination, and maximum lesion diameter on MRI had an AUC of 73% on internal validation and formed the basis of the nomogram. Addition of other MRI or biopsy information did not significantly improve the model performance. Using a cutoff of 25%, the proportion of patients eligible for FT was 89% at the cost of missing 30 patients (10%) with unfavorable disease. External validation is required before the nomogram can be used in clinical practice. CONCLUSIONS: We report the first nomogram that improves selection criteria for FT and limits the risk of undertreatment. PATIENT SUMMARY: We conducted a study to develop a better way of selecting patients for focal therapy for localized prostate cancer. A novel predictive tool was developed using the prostate-specific antigen (PSA) level measured before biopsy, tumor stage assessed via digital rectal examination, and lesion size on magnetic resonance imaging (MRI) scans. This tool improves the prediction of unfavorable disease and may reduce the risk of undertreatment of localized prostate cancer when using focal therapy.

Magnetic Resonance Imaging Follow-up of Targeted Biopsy-negative Prostate Lesions.

BACKGROUND: The optimal radiological follow-up of prostate lesions negative on magnetic resonance imaging (MRI)-targeted biopsy (MRI-TB) is yet to be optimised. OBJECTIVE: To present medium-term radiological and clinical follow-up of biopsy-negative lesions. DESIGN, SETTING, AND PARTICIPANTS: The records for men who underwent multiparametric MRI at the UCLH one-stop clinic for suspected prostate cancer between September 2017 and March 2020 were reviewed (n = 1199). Patients with Likert 4 or 5 lesions were considered (n = 495), and those with a subsequent negative MRI-TB comprised the final study population (n = 91). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline and follow-up MRI and biopsy data (including prostate-specific antigen [PSA], prostate volume, radiological scores, and presence of any noncancerous pathology) were extracted from reports. The last follow-up date was the date of the last test or review in clinic. RESULTS AND LIMITATIONS: Median follow-up was 1.8 yr (656 d, interquartile range [IQR] 359-1008). At baseline, the median age was 65.4 yr (IQR 60.7-70.0), median PSA was 7.1 ng/ml (IQR 4.7-10.0), median prostate volume was 54 ml (IQR 39.5-75.0), and median PSA density (PSAD) was 0.13 ng/ml2 (IQR 0.09-0.18). Eighty-six men (95%) had Likert 4 lesions, while the remaining five (5%) had Likert 5 lesions. Only 21 men (23%) had a single lesion; most had at least two. Atrophy was the most prevalent pathology on MRI-TB, present in 64 men (74%), and followed by acute inflammation in 42 (46%), prostatic intraepithelial neoplasia in 33 (36%), chronic inflammation in 18 (20%), atypia in 13 (14%), and granulomatous inflammation in three (3%). Fifty-eight men had a second MRI study (median 376 d, IQR 361-412). At the second MRI, median PSAD decreased to 0.11 ng/ml2 (IQR 0.08-0.18). A Likert 4 or 5 score persisted only in five men (9%); 40 men (69%) were scored Likert 3, while the remaining 13 (22%) were scored Likert 2 (no lesion). Of 45 men with a Likert ≥3 score, most only had one lesion at the second MRI (28 men; 62%). Of six men with repeat MRI-TB during the study period, two were subsequently diagnosed with prostate cancer and both had persistent Likert 4 scores (at baseline and at least one follow-up MRI). CONCLUSIONS: Most biopsy-negative MRI lesions in the prostate resolve over time, but any persistent lesions should be closely monitored. PATIENT SUMMARY: Lesions in the prostate detected via magnetic resonance imaging (MRI) scans that are negative for cancer on biopsy usually resolve. Repeat MRI can indicate persistent lesions that might need a second biopsy.

Association Between 5α-Reductase Inhibitors and Prostate Cancer Mortality: A Systematic Review and Meta-analysis.

Importance: Recently, several large, high-quality analyses have shown opposing results regarding the association between 5α-reductase inhibitor (5-ARI) use and prostate cancer (PCa) mortality. Objective: To systematically evaluate the current evidence regarding 5-ARI use and PCa mortality. Data Sources: A literature search began in and was conducted through August 2022 using PubMed/Medline, Embase, and Web of Science databases. Study Selection: Studies were deemed eligible if they included male patients of any age who were 5-ARI users and were compared with those who were nonusers if they analyzed PCa mortality in randomized clinical trials and prospective or retrospective cohort studies. Data Extraction and Synthesis: This study was reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Adjusted hazard ratios (HRs) were extracted from published articles. Data analysis was performed in August 2022. Main Outcomes and Measures: The primary outcome was PCa mortality among 5-ARI users vs nonusers. The inverse variance method with adjusted HRs and random-effect models were used to determine the association between 5-ARI use and PCa mortality. Two subgroup analyses were performed to assess the effect of 2 main confounders: prostate-specific antigen level and PCa diagnosis at baseline. Results: Among 1200 unique records screened, 11 studies met the inclusion criteria. A total of 3 243 575 patients were included: 138 477 users of 5-ARI and 3 105 098 nonusers. There was no statistically significant association between 5-ARI use and PCa mortality (adjusted HR, 1.04; 95% CI, 0.80-1.35; P = .79). No significant association was found when the analysis was restricted to studies that excluded patients with a diagnosis of PCa at baseline (adjusted HR, 1.00; 95% CI, 0.60-1.67; P = .99) or the analysis was restricted to prostate-specific antigen-adjusted studies (adjusted HR, 0.76; 95% CI, 0.57-1.03; P = .08). Conclusions and Relevance: This systematic review and meta-analysis, which draws on 2 decades of epidemiologic literature and includes more than 3 million patients, found no statistically significant association between 5-ARI use and PCa mortality but provides important data to inform clinical care.

Expanding inclusion criteria for active surveillance in intermediate-risk prostate cancer: a machine learning approach.

PURPOSE: To develop new selection criteria for active surveillance (AS) in intermediate-risk (IR) prostate cancer (PCa) patients. METHODS: Retrospective study including patients from 14 referral centers who underwent pre-biopsy mpMRI, image-guided biopsies and radical prostatectomy. The cohort included biopsy-naive IR PCa patients who met the following inclusion criteria: Gleason Grade Group (GGG) 1-2, PSA < 20 ng/mL, and cT1-cT2 tumors. We relied on a recursive machine learning partitioning algorithm developed to predict adverse pathological features (i.e., ≥ pT3a and/or pN + and/or GGG ≥ 3). RESULTS: A total of 594 patients with IR PCa were included, of whom 220 (37%) had adverse features. PI-RADS score (weight:0.726), PSA density (weight:0.158), and clinical T stage (weight:0.116) were selected as the most informative risk factors to classify patients according to their risk of adverse features, leading to the creation of five risk clusters. The adverse feature rates for cluster #1 (PI-RADS ≤ 3 and PSA density < 0.15), cluster #2 (PI-RADS 4 and PSA density < 0.15), cluster #3 (PI-RADS 1-4 and PSA density ≥ 0.15), cluster #4 (normal DRE and PI-RADS 5), and cluster #5 (abnormal DRE and PI-RADS 5) were 11.8, 27.9, 37.3, 42.7, and 65.1%, respectively. Compared with the current inclusion criteria, extending the AS criteria to clusters #1 + #2 or #1 + #2 + #3 would increase the number of eligible patients (+ 60 and + 253%, respectively) without increasing the risk of adverse pathological features. CONCLUSIONS: The newly developed model has the potential to expand the number of patients eligible for AS without compromising oncologic outcomes. Prospective validation is warranted.

Risk stratification for early biochemical recurrence of prostate cancer in the era of multiparametric magnetic resonance imagining-targeted biopsy.

BACKGROUND: Multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy are nowadays recommended in the prostate cancer (PCa) diagnostic pathway. Ploussard and Mazzone have integrated these tools into novel risk classification systems predicting the risk of early biochemical recurrence (eBCR) in PCa patients who underwent radical prostatectomy (RP). We aimed to assess available risk classification systems and to define the best-performing. METHODS: Data on 1371 patients diagnosed by MRI-targeted biopsy and treated by RP between 2014 and 2022 at eight European tertiary referral centers were analyzed. Risk classifications systems included were the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) risk groups, the Cancer of the Prostate Risk Assessment (CAPRA) score, the International Staging Collaboration for Cancer of the Prostate (STAR-CAP) classification, the Ploussard and Mazzone models, and ISUP grade group. Kaplan-Meier analyses were used to compare eBCR among risk classification systems. Performance was assessed in terms of discrimination quantified using Harrell's c-index, calibration, and decision curve analysis (DCA). RESULTS: Overall, 152 (11%) patients had eBCR at a median follow-up of 31 months (interquartile range: 19-45). The 3-year eBCR-free survival rate was 91% (95% confidence interval [CI]: 89-93). For each risk classification system, a significant difference among survival probabilities was observed (log-rank test p < 0.05) except for NCCN classification (p = 0.06). The highest discrimination was obtained with the STAR-CAP classification (c-index 66%) compared to CAPRA score (63% vs. 66%, p = 0.2), ISUP grade group (62% vs. 66, p = 0.07), Ploussard (61% vs. 66%, p = 0.003) and Mazzone models (59% vs. 66%, p = 0.02), and EAU (57% vs. 66%, p < 0.001) and NCCN (57% vs. 66%, p < 0.001) risk groups. Risk classification systems demonstrated good calibration characteristics. At DCA, the CAPRA score showed the highest net benefit at a probability threshold of 9%-15%. CONCLUSIONS: The performance of risk classification systems using MRI and MRI-targeted information was less optimistic when tested in a contemporary set of patients. CAPRA score and STAR-CAP classification were the best-performing and should be preferred for treatment decision-making.