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.

External validation and comparison of magnetic resonance imaging-based risk prediction models for prostate biopsy stratification.

PURPOSE: Magnetic resonance imaging (MRI) is a promising tool for risk assessment, potentially reducing the burden of unnecessary prostate biopsies. Risk prediction models that incorporate MRI data have gained attention, but their external validation and comparison are essential for guiding clinical practice. The aim is to externally validate and compare risk prediction models for the diagnosis of clinically significant prostate cancer (csPCa). METHODS: A cohort of 4606 patients across fifteen European tertiary referral centers were identified from a prospective maintained database between January 2016 and April 2023. Transrectal or transperineal image-fusion MRI-targeted and systematic biopsies for PI-RADS score of ≥ 3 or ≥ 2 depending on patient characteristics and physician preferences. Probabilities for csPCa, defined as International Society of Urological Pathology (ISUP) grade ≥ 2, were calculated for each patients using eight models. Performance was characterized by area under the receiver operating characteristic curve (AUC), calibration, and net benefit. Subgroup analyses were performed across various clinically relevant subgroups. RESULTS: Overall, csPCa was detected in 2154 (47%) patients. The models exhibited satisfactory performance, demonstrating good discrimination (AUC ranging from 0.75 to 0.78, p < 0.001), adequate calibration, and high net benefit. The model described by Alberts showed the highest clinical utility for threshold probabilities between 10 and 20%. Subgroup analyses highlighted variations in models' performance, particularly when stratified according to PSA level, biopsy technique and PI-RADS version. CONCLUSIONS: We report a comprehensive external validation of risk prediction models for csPCa diagnosis in patients who underwent MRI-targeted and systematic biopsies. The model by Alberts demonstrated superior clinical utility and should be favored when determining the need for a prostate biopsy.

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.

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.

Optimizing multiparametric magnetic resonance imaging-targeted biopsy and prostate cancer grading accuracy.

PURPOSE: To assess the most efficient biopsy method to improve International Society of Urological Pathology (ISUP) grade group accuracy with final pathology of the radical prostatectomy (RP) specimen in the era of magnetic resonance imaging (MRI)-driven pathway. METHODS: A total of 753 patients diagnosed by transrectal MRI-targeted and systematic biopsies (namely "standard method"), treated by RP, between 2016 and 2021 were evaluated. Biopsy methods included MRI-targeted biopsy, side-specific systematic biopsies relative to index MRI lesion and combination of both. Number of MRI-targeted biopsy cores and positive cores needed per index MRI lesion were assessed. Multivariable analysis was performed to analyze predictive factors of upgrading using MRI targeted and ipsilateral systematic biopsies method. RESULTS: Overall, ISUP grade group accuracy varied among biopsy methods with upgrading rate of 35%, 49%, 27%, and 24% for MRI targeted, systematic, MRI targeted and ipsilateral systematic biopsies and standard methods, respectively (p < 0.001). A minimum of two positive MRI-targeted biopsies cores per index MRI lesion were required when testing MRI targeted and ipsilateral systematic biopsies method to reach equivalent accuracy compared to standard method. Omitting contralateral systematic biopsies spared an average of 5.9 cores per patient. At multivariable analysis, only the number of positive MRI-targeted biopsy cores per index MRI lesion was predictive of upgrading. CONCLUSION: MRI targeted and ipsilateral systematic biopsies allowed an accurate definition of ISUP grade group and appears to be an interesting alternative when compared with standard method, reducing total number of biopsy cores needed.

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.

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.

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.

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.

Optimal PSA density threshold and predictive factors for the detection of clinically significant prostate cancer in patient with a PI-RADS 3 lesion on MRI.

INTRODUCTION: While Prostate Imaging Reporting and Data System (PI-RADS) 4 and 5 lesions usually justify prostate biopsy (PBx), the management of a PI-RADS 3 lesion can be discussed. The aim of our study was to determine the optimal prostate-specific antigen density (PSAD) threshold and predictive factors of clinically significant prostate cancer (csPCa) in patients with a PI-RADS 3 lesion on MRI. PATIENTS AND METHODS: Using our prospectively maintained database, we conducted a monocentric retrospective study, including all patients with a clinical suspicious of prostate cancer (PCa), all of them had a PI-RADS 3 lesion on the mpMRI prior to PBx. Patients under active surveillance or displaying suspicious digital rectal examination were excluded. Clinically significant (csPCa) was defined as PCa with any ISUP grade group ≥ 2 (Gleason ≥ 3 + 4). RESULTS: We included 158 patients. The detection rate of csPCa was 22.2%. In case of PSAD ≤ 0.15 ng/ml/cm3, PBx would be omitted in 71.5% (113/158) of men at the cost of missing 15.0% (17/113) of csPCa. With a threshold of 0.15 ng/ml/cm3, the sensitivity and the specificity were 0.51 and 0.78 respectively. The positive predictive value was 0.40 and the negative predictive value was 0.85. According to multivariate analysis, age (OR = 1.10, CI95% 1.03-1.19, P = 0.007), and PSAD ≥ 0.15 ng/ml/cm3 (OR = 3.59, CI95% 1.41-9.47, P = 0.008) were independent predictive factors of csPCa. Previous negative PBx was negatively associated with csPCa (OR = 0.24, CI 95% 0.07-0.66, P = 0.01). CONCLUSION: Our result suggests that the optimal PSAD threshold was 0.15 ng/ml/cm3. However, in this case omitting PBx in 71.5% of cases would be at the cost of missing 15.0% of csPCa. PSAD should not be used alone, other predictive factors as age and PBx history should also be considered in the discussion with the patient, to avoid PBx while missing few csPCa.

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.

Impact of age on the Quadrella index assessing oncological and functional results after prostate brachytherapy: A 6-year analysis.

Purpose: As the oncological results of prostate brachytherapy (BT) are excellent for low-risk (LR) or favorable intermediate-risk (FIR) prostate cancer (PCa), evaluating the side effects has become a major issue, especially for young men. The objective of the study was to compare the oncologic and functional results of BT using Quadrella index for patients aged 60 or less compared with older patients. Material and methods: From June, 2007 to June, 2017, 222 patients, including 70 ≤ 60 years old and 152 > 60 years old, underwent BT for LR-FIR PCa, with good erectile function at baseline according to International Index of Erectile Function-5 (IIEF-5) > 16. Quadrella index was achieved under the following circumstances: 1) Absence of biological recurrence (Phoenix criteria); 2) Absence of erectile dysfunction (ED) (IIEF-5 > 16); 3) No urinary toxicity (international prostate score symptom) IPSS < 15 or IPSS > 15, and ΔIPSS < 5; 4) No rectal toxicity (RT) (Radiation Therapy Oncology Group, RTOG = 0). Patients were treated on demand with phosphodiesterase inhibitors (PDE5i) post-operatively. Results: The Quadrella index was satisfied for about 40-80% of patients ≤ 60 years vs. 33-46% for older patients during 6-year follow-up (significant difference from the second year). At year 5, 100% of evaluable patients aged ≤ 60 and 91.8% > 60 (p = 0.29) reached Phoenix criteria. The criterion of ED (IIEF-5 < 16) largely explained the validity rate of Quadrella alone. There was no ED for 67.2-81.4% of patients ≤ 60 years compared with 40.0-56.1% for patients > 60 (significant difference since year 4 in favor of young men). After two years of follow-up, more than 90% of patients in both the groups showed neither urinary nor rectal toxicities. Conclusions: For young men displaying LR-FIR PCa, BT appears to be a first-class therapeutic option, as the oncological results were at least equivalent to those of older patients with good long-term tolerance.

Expanding Active Surveillance Criteria for Low- and Intermediate-risk Prostate Cancer: Can We Accurately Predict the Risk of Misclassification for Patients Diagnosed by Multiparametric Magnetic Resonance Imaging-targeted Biopsy?

Models predicting the risk of adverse pathology (ie, International Society of Urological Pathology [ISUP] grade group ≥3, pT3, and/or pN1) among patients operated by radical prostatectomy (RP) have been proposed to expand active surveillance (AS) inclusion criteria. We aimed to test these models in a set of 1062 low-risk and favorable intermediate-risk prostate cancer (PCa) patients diagnosed by multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy. We hypothesized that the inclusion of radiological features into a novel model would improve patient selection. Performance was assessed using discrimination, calibration, and decision curve analysis (DCA). Available models were characterized by poor discrimination (areas under the receiver operating characteristic curve [AUCs] of 59% and 60%), underestimation of predicted risk on calibration plots, and a small amount of net benefit against a probability threshold of 40-50% at the DCA. The development of a novel model slightly improved discrimination (AUC of 63% vs 59%, p = 0.001, and 63% vs 60%, p = 0.07) and net benefit against threshold probabilities of ≥30%. This first multicenter study demonstrated the poor performance of models predicting adverse pathology and that implementation of MRI and MRI-targeted biopsy in this setting was not associated with a clear improvement in patient selection. Patients harboring low-risk or favorable intermediate-risk PCa and candidates for RP cannot be referred accurately to an AS program without a non-negligible risk of misclassification. PATIENT SUMMARY: We tested prediction models that could expand the selection of prostate cancer patients for active surveillance. Models were inaccurate and associated with a high risk of misclassification despite the implementation of multiparametric magnetic resonance imaging and targeted biopsies.

External Validation of Models for Prediction of Side-specific Extracapsular Extension in Prostate Cancer Patients Undergoing Radical Prostatectomy.

BACKGROUND: Predicting the risk of side-specific extracapsular extension (ECE) is essential for planning nerve-sparing radical prostatectomy (RP) in patients with prostate cancer (PCa). OBJECTIVE: To externally validate available models for prediction of ECE. DESIGN, SETTING, AND PARTICIPANTS: Sixteen models were assessed in a cohort of 737 consecutive PCa patients diagnosed via multiparametric magnetic resonance imaging (MRI)-targeted and systematic biopsies and treated with RP between January 2016 and November 2021 at eight referral centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Model performance was evaluated in terms of discrimination using area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA). RESULTS AND LIMITATIONS: Overall, ECE was identified in 308/1474 (21%) prostatic lobes. Prostatic lobes with ECE had higher side-specific clinical stage on digital rectal examination and MRI, number of positive biopsy cores, and International Society of Urological Pathology grade group in comparison to those without ECE (all p < 0.0001). Less optimistic performance was observed in comparison to previous published studies, although the models described by Pak, Patel, Martini, and Soeterik achieved the highest accuracy (AUC ranging from 0.73 to 0.77), adequate calibration for a probability threshold <40%, and the highest net benefit for a probability threshold >8% on DCA. Inclusion of MRI-targeted biopsy data and MRI information in models improved patient selection and clinical usefulness. Using model-derived cutoffs suggested by their authors, approximately 15% of positive surgical margins could have been avoided. Some available models were not included because of missing data, which constitutes a limitation of the study. CONCLUSIONS: We report an external validation of models predicting ECE and identified the four with the best performance. These models should be applied for preoperative planning and patient counseling. PATIENT SUMMARY: We validated several tools for predicting extension of prostate cancer outside the prostate gland. These tools can improve patient selection for surgery that spares nerves affecting recovery of sexual potency after removal of the prostate. They could potentially reduce the risk of finding cancer cells at the edge of specimens taken for pathology, a finding that suggests that not all of the cancer has been removed.

Magnetic Resonance Imaging-based T-staging to Predict Biochemical Recurrence after Radical Prostatectomy: A Step Towards the iTNM Classification.

BACKGROUND: Local staging of prostate cancer (PCa) still relies on digital rectal examination (DRE), which therefore remains the standard for risk stratification in guideline recommendations, clinical trials, and patient counseling. This issue is increasingly controversial as multiparametric magnetic resonance imaging (mpMRI) has become the most influential diagnostic tool for local staging of PCa over the past two decades. OBJECTIVE: To compare various models of T category based on DRE or mpMRI to predict early biochemical recurrence (BCR) after radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter cohort study was conducted between 2014 and 2021. A total of 1436 patients were recruited across eight referral centers in France, Italy, Switzerland, and Belgium. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: BCR was defined as two prostate-specific antigen values of ≥0.2 ng/ml during follow-up. Harrell's concordance index (C index) was used to compare the discrimination of four models of T staging based on DRE (model 1: cT1 vs cT2 vs cT3) or mpMRI (model 2: organ-confined disease vs extracapsular extension [iECE] vs seminal vesicle invasion [iSVI]; model 3: Prostate Imaging-Reporting and Data System [PI-RADS] ≤3 vs PI-RADS 4 vs PI-RADS 5; and model 4: iT2a [PI-RADS ≤3] vs iT2b [PI-RADS 4] vs iT2c [PI-RADS 5 excluding ECE or SVI] vs iT3a [ECE] vs iT3b [SVI]) to predict BCR. RESULTS AND LIMITATIONS: Overall, 74 (5%), 845 (59%), 482 (34%), and 35 (2%) patients had low-, intermediate-, high-, and very high-risk PCa, respectively, according to the Mazzone risk classification. After median follow-up of 16 mo, 113 patients experienced BCR. Although the new five-group mpMRI-based T classification system (model 4) had the highest prognostic discrimination (C index 0.694) for predicting early BCR on multivariable analysis, there was overlap between the 95% confidence intervals of the models. On sensitivity analysis, the new mpMRI-based T staging still had a higher C index than DRE for predicting BCR when excluding cN1 patients and comparing it with a five-group DRE-based T classification (cT1c vs cT2a vs cT2b vs cT2c vs cT3), but the overlap between the 95% confidence intervals of the models remained. The main limitation is the short follow-up. CONCLUSIONS: We described an alternative mpMRI-based T staging for prediction of early BCR after RP for PCa. Our results need to be validated externally before they can be applied in clinical practice. PATIENT SUMMARY: At present, digital rectal examination of the prostate is used to stage prostate cancer. We developed an alternative model for staging that uses information from magnetic resonance imaging (MRI) scans to predict cancer outcomes for men undergoing surgical removal of the prostate.

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.

Impact of Multiparametric MRI and PSA Density on the Initial Indication or the Maintaining in Active Surveillance During Follow-Up in low-Risk Prostate Cancer.

INTRODUCTION: A greater selection of candidates for active surveillance (AS) of prostate cancer (PCa) may decrease the rate of delayed treatment. We aimed to study: 1) the impact of MRI and PSA density (PSAd) at baseline on the final status, and 2) the impact of bio-clinical features during the follow-up on pursuing AS. MATERIALS AND METHODS: This retrospective, monocentric study between June 2013 and July 2020, included 99 patients in AS (median follow-up: 19 months [18-92]). All MRI were reviewed by a single radiologist. Lost to follow-up were 17 patients and 6 patients chose treatment by themselves. Treatment was proposed in case of upgrading (≥ GG2) or increasing PCa volume. RESULTS: Impact of MRI and PSAd at baseline:  Combining PSAd ≤ 0.15 and PIRADS ≤ 3, the probability to remain in AS was 72%. This rate reached 83% when PSAd ≤ 0.10 was associated to normal MRI.  During follow-up:  One hundred fifty-seven prostatic biopsies (PBx) were performed and 38 (24%) found PCa upgrading. The association between negative MRI and PSAd ≤ 0.10, during follow-up, had an excellent NPV to predict treatment (95%). This combination concerned 25% (37/151) of surveillance biopsies that could have been avoided at the cost of delaying upgrading in 3% (1/37). In multivariate analysis, only PIRADS ≥ 4 before PBx was associated to a risk of treatment during follow-up (OR, 10.4 [95% CI, 4.2-25.8]; P < .0001). CONCLUSION: Using PSAd and MRI at baseline to select patients showed excellent performances to predict the maintenance in AS. During follow-up, MRI PIRADS ≥ 4 was associated to an increased risk of treatment.

Stratifying patients with intermediate-risk prostate cancer: Validation of a new model based on MRI parameters and targeted biopsy and comparison with NCCN and AUA subclassifications.

OBJECTIVE: Intermediate-risk prostate cancer regroups heterogeneous patients with different oncologic outcomes. Aim of the study is to validate a novel intermediate-risk subclassification ("magnetic resonance imaging [MRI] subclassification") that defines favorable and unfavorable diseases based on multiparametric MRI parameters and compare it to NCCN and AUA intermediate-risk subclassifications. METHODS: A total of 429 patients treated with radical prostatectomy for NCCN intermediate-risk prostate cancer were identified. Using MRI subclassification, a favorable disease was defined as an organ-confined disease on MRI and international society of urological pathology Grade Group 1 to 2 on targeted biopsy. Remaining was classified as unfavorable. Univariable and multivariable analysis tested MRI subclassification in predicting overall unfavorable disease (OUD: pT3-4 and/or pN1 and/or International Society of Urological Pathology Grade Group ≥ 3), the need for adjuvant therapy and early biochemical recurrence (eBCR). Performance of NCCN, AUA, and MRI models was compared in term of OUD proportion and eBCR prediction using Harrell's c-index, calibrations plots, and decision curve analysis. RESULTS: Median (interquartile range) follow-up was 12 months (4-28). In multivariable analysis, MRI subclassification was an independent factor for OUD (odds ratio [OR]: 4.54 [2.85-7.22], P < 0.001), the need for adjuvant therapy (OR: 3.42 [1.36-8.57], P = 0.009), and eBCR (HR: 2.62 [1.18-5.83], P = 0.018). Using this model, the proportion of unfavorable disease decreased from 73.7% and 63.9% to 35.9% (P < 0.001) associated to an increasing proportion of OUD when compared to NCCN and AUA models (63.9% and 67.1%-77.9% respectively, P < 0.001). Performance of the 3 models for eBCR prediction tended to be similar with a poor accuracy ranged from 58.7% to 66.7% (P > 0.05), permanent miscalibration and a net benefit at decision curve analysis. CONCLUSIONS: We validated an intermediate-risk subclassification based on MRI and targeted biopsy that potentially improves patient selection by reducing the number of patients considered at unfavorable risk while increasing proportion of patients harboring poor oncologic outcomes. Its performance for eBCR detection was comparable to NCCN and AUA models.

External validation of the Briganti nomogram predicting lymph node invasion in patients with intermediate and high-risk prostate cancer diagnosed with magnetic resonance imaging-targeted and systematic biopsies: A European multicenter study.

OBJECTIVE: To validate a nomogram predicting lymph node invasion (LNI) in prostate cancer patients undergoing radical prostatectomy taking into consideration multiparametric-magnetic resonance imaging (mp-MRI) parameters and targeted biopsies in a western European cohort. PATIENTS AND METHODS: A total of 473 men diagnosed by targeted biopsies, using software-based MRI-ultrasound image fusion system, and operated by radical prostatectomy with extended pelvic lymph node dissection across 11 Europeans centers between 2012 and 2019 were identified. Area under the curve of the receiver operator characteristic curve, calibration plot and decision curve analysis were used to evaluated the performance of the model. RESULTS: Overall, 56 (11.8%) patients had LNI on final pathologic examination with a median (IQR) of 13 (9-18) resected nodes. Significant differences (all P < 0.05) were found between patients with and without LNI in terms of preoperative PSA, clinical stage at DRE and mp-MRI, maximum diameter of the index lesion, PI-RADS score, Grade Group on systematic and targeted biopsies, total number of dissected lymph nodes, final pathologic staging and Grade Group. External validation of the prediction model showed a good accuracy with an area under the curve calculated as 0.8 (CI 95% 0.75-0.86). Graphic analysis of calibration plot and decision curve analysis showed a slight underestimation for predictive probability for LNI between 3% and 22% and a high net benefit. A cut-off at 7% was associated with a risk of missing LNI in 2.6%, avoiding unnecessary surgeries in 55.9%. CONCLUSIONS: We report an external validation of the nomogram predicting LNI in patients treated with extended pelvic lymph node dissection in a western European cohort and a cut-off at 7% seems appropriate.

Prospective four years of evaluation of erectile function after low-dose-rate prostate brachytherapy using baseline IIEF-5 > 16.

PURPOSE: Prostate brachytherapy (BT) is a validated treatment for localized prostate cancer (CaP) and an attractive therapy option for patients seeking to preserve erectile function (EF). The aim of this paper is to prospectively assess EF evolution during 4 years after BT. MATERIAL AND METHODS: Between February 2007 and July 2012, 179 patients underwent an exclusive Iodine-125 BT, for low-intermediate favorable risk CaP of whom, 102 had an initial international index of erectile function 5 score (IIEF-5) > 16 and were included in the study. Of those, 12.7% received neo-adjuvant hormonotherapy (HT) to decrease the prostate volume. Post-BT intake of phosphodiesterase inhibitors (PDE5i) was not an exclusion criterion. Erectile function was prospectively assessed using a validated questionnaire IIEF-5 before treatment and annually for 4 years. RESULTS: At 1-year follow-up, 54% of patients preserved an IIEF-5 > 16 and only 8% suffered from severe ED. During the next 3 years, the results were not statistically different. The mean IIEF-5 lost 4 points during the first year, 17 vs. 21, and remained stable during the following 3 years. We did not find any significant differences in the proportion of patients treated by PDE5i (18-20%). As for patients with a normal preoperative IIEF-5 (> 21) (n = 52), 35-42% preserved a normal EF and 71-77% maintained an IIEF-5 > 16, including 13-19% of patients who needed PDE5i. Those results were stable for over 4 years. CONCLUSIONS: During the first 4 years after BT, more than half of patients maintained an IIEF-5 > 16, and EF results remained stable. Severe erectile dysfunction (ED) was very rare.