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.

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.

Does using a laser improve outcomes of conventional circumcision in adult and children populations? Results from a systematic review and meta-analysis.

BACKGROUND: Male circumcision is a well-known old surgery, and several recently developed techniques have been scaled up, including the introduction of laser technology, as alternative approaches to overcome morbidity of conventional surgery scalpel/suture method OBJECTIVES: We aimed to perform a systematic review and meta-analysis of studies comparing laser circumcision versus conventional circumcision technique in terms of perioperative outcomes and efficacy (complications, unacceptable appearance, reoperation rate) both in children and adults. MATERIALS AND METHODS: This review was performed following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. Continuous variables were analyzed using the inverse variance of the mean difference with a random effect, 95% confidence interval (CI), and p-value. The incidence of complications, unacceptable appearance, and reoperation rate were pooled using the Cochran-Mantel-Haenszel Method with the random effect model and reported as odds ratio (OR), 95% CI, and p-value. Significance was set at p-value ≤0.05 and 95%CI. RESULTS: Seven studies were included. In comparison to the conventional circumcision, laser circumcision shoved lower visual analogue score at 24-h, and 7 days after surgery, a lower rate of overall complication rate (OR 0.33, 95% CI 0.24-0.47, p < 0.001), scarring (OR 0.09, 95% CI 0.02, 0.41, p = 0.002), and unacceptable appearance (OR 0.09, 95% CI 0.05, 0.15, p < 0.001). We found no statistically significant difference in surgical time, and incidence of bleeding, infection, wound dehiscence, and reoperation rate. DISCUSSION AND CONCLUSION: Our review infers that laser-assisted circumcision is certainly a safe and strong contender as the procedure of choice in both children and adult populations.

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.

MRI/US fusion prostate biopsy in men on active surveillance: Our experience.

AIM: The upgrading or staging in men with prostate cancer (PCA) undergoing active surveillance (AS), defined as Gleason score (GS) ≥ 3+4 or more than 2 area with cancer, was investigated in our experience using the software-based fusion biopsy (FB). METHODS: We selected from our database, composed of 620 biopsies, only men on AS according to criteria of John Hopkins Protocol (T1c, < 3 positive cores, GS = 3+3 = 6). Monitoring consisted of PSA measurement every 3 months, a clinical examination every 6 months, confirmatory FB within 6 months and then annual FB in all men. The suspicious MRI lesions were scored according to the Prostate Imaging Reporting and Data System (PI-RADS) classification version 2. FB were performed with a transrectal elastic free-hand fusion platform. The overall and clinically significant cancer detection rate was reported. Secondary, the diagnostic role of systematic biopsies was evaluated. RESULTS: We selected 56 patients on AS with mean age 67.4 years, mean PSA 6.7 ng/ml and at least one follow-up MRI-US fusion biopsy (10 had 2 or 3 follow-up biopsies). Lesions detected by MRI were: PIRADS-2 in 5, PIRADS-3 in 28, PIRADS-4 in 18 pts and PIRADS-5 in 5 patients. In each MRI lesion, FB with 2.1 ± 1.1 cores were taken with a mean total cores of 13 ± 2.4 including the systematic cores. The overall cancer detection rate was 71% (40/56): 62% (25/40) in target core and 28% (15/40) in systematic core. The overall significant cancer detection rate was 46% (26/56): 69% (18/26) in target vs 31% (8/26) in random cores. CONCLUSIONS: The incidence of clinical significant cancer was 46% in men starting active surveillance, but it was more than doubled using MRI/US Target Biopsy 69% (18/26) rather than random cores (31%, 8/26). However, 1/3 of disease upgrades would have been missed if only the targeted biopsies were performed. Based on our experience, MRI/US fusion target biopsy must be associated to systematic biopsies to improve detection of significant cancer, reducing the risks of misclassification.

Accuracy of elastic fusion biopsy in daily practice: Results of a multicenter study of 2115 patients.

OBJECTIVES: To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice. METHODS: We retrospectively enrolled 2115 patients from 15 institutions in four European countries undergoing transrectal Koelis fusion biopsy from 2010 to 2017. A variable number of target (usually 2-4) and random cores (usually 10-14) were carried out, depending on the clinical case and institution habits. The overall and clinically significant prostate cancer detection rates were assessed, evaluating the diagnostic role of additional random biopsies. The cancer detection rate was correlated to multiparametric magnetic resonance imaging features and clinical variables. RESULTS: The mean number of targeted and random cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0), respectively. The cancer detection rate of Koelis biopsies was 58% for all cancers and 43% for clinically significant prostate cancer. The performance of additional, random cores improved the cancer detection rate of 13% for all cancers (P < 0.001) and 9% for clinically significant prostate cancer (P < 0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively. Clinical stage and Prostate Imaging Reporting and Data System score were predictors of prostate cancer detection in multivariate analyses. Prostate-specific antigen was associated with prostate cancer detection only for clinically significant prostate cancer. CONCLUSIONS: Koelis fusion biopsy offers a good cancer detection rate, which is increased in patients with a high Prostate Imaging Reporting and Data System score and clinical stage. The performance of additional, random cores seems unavoidable for correct sampling. In our experience, the Prostate Imaging Reporting and Data System score and clinical stage are predictors of prostate cancer and clinically significant prostate cancer detection; prostate-specific antigen is associated only with clinically significant prostate cancer detection, and a higher number of biopsy cores are not associated with a higher cancer detection rate.

Blue light cystoscopy with hexylaminolevulinate: Our 7 years experience.

AIM: The objective of the present study is to evaluate the diagnostic accuracy of hexylaminolevulinate (HAL) blue light cystoscopy compared with standard white light cystoscopy (WLC) in daily practice. MATERIALS AND METHODS: An observational, comparative, controlled (within patient) study was carried out at our Center. 61 consecutive patients with suspected or confirmed bladder cancer were recruited for the study from January 2008 until January 2015. Patients with suspected bladder cancer (positive cytology with negative WLC) or history of previous high-grade NMIBC or CIS were included in the study. Biopsies/resection of each positive lesion/suspicious areas were always taken after the bladder was inspected under WLC and BLC. Diagnoses of bladder tumor or CIS were considered as positive results, and the presence of normal urothelium in the biopsy specimen as negative result. RESULTS: 61 BLC were performed. 15/61 (24.5%) with suspected initial diagnosis of NMIBC and 46/61 (75.5%) with a history of high-risk non-muscle invasive bladder cancer (NMIBC). We performed a total of 173 biopsies/TURBT of suspicious areas: 129 positive only to the BLC and 44 both positive to WLC and BLC. 84/173 biopsies/TURBT were positive for cancer. All 84 NMIBC were positive to the BLC, while 35/84 were positive to the WLC with a sensitivity of BLC and WLC respectively of 100% and 41.7%. Sensitivity of WLC for highgrade NMIBC and CIS was 34.1% and 39% respectively while sensitivity of BLC for high-grade NMIBC and CIS was 100%. The specificity of the WLC was 79.9% compared to 48.5% of the BLC. The positive predictive value of BLC and WLC were respectively 48% (95% CI: 0.447-0.523) and 79% (95% CI: 0.856-0.734). CONCLUSIONS: Our data confirm those reported in the literature: BLC increases the detection rate of NMIBC particularly in high risk patients (history of CIS or high grade). BLC is a powerful diagnostic tool in the diagnosis of bladder cancer if malignancy is suspected (positive urine cytology) and if conventional WLC is negative.

MRI/US fusion prostate biopsy: Our initial experience.

AIM: The objective of this study is to present our initial experience with magnetic resonance imaging/ultrasound (MRI/US) fusion biopsy using the Koelis Trinity device after the first consecutive 59 patients. MATERIALS AND METHODS: 59 consecutive patients with suspected prostate cancer (PCA) underwent prostate biopsy using Trinity Koelis® (Koelis, Grenoble, France). We divided the patients into 2 groups: patients with a previous negative mapping underwent to a MRI/US fusion re-biopsy (Group A); and biopsy-naïve patients who underwent to a first stereotactic 3-D mapping of the prostate (Group B). Group A (22 patients):mean age 64 years (CI 48-73), mean PSA = 7.7 ng/ml (CI 4.2- 9.9); mean prostate volume 55 ml(CI 45-82), Digital Rectal Examination (DRE) positive in 2/22, number of lesions detected by MRI 1.4, mean cores from each MRI target lesion 3 (CI 2-5), mean total cores 15 ( CI 12-19). Group B (37 patients): mean age 66 years (CI 49-77), mean PSA= 4.7 (3.2- 7.9); mean prostate volume 45 ml (33-67), DRE positive in 5/37, mean total cores 14 ( CI 10-16) Results: In Group A 10/22 patients were positive for PCA (overall detection rate of 45.5%): 6 PCA were detected by target biopsy and 4 cancer by random biopsy. Significant prostate cancer (defined as the presence of Gleason pattern 4) was detected in 4/10 patients (Significant PCA detection rate of 40%) and all significant PCA were detected by MRI target biopsy. All PCA detected by random biopsy had Gleason score 3 + 3 = 6. In Group B (biopsy naïve patients) 14/37 patients were positive for PCA (overall detection rate of 37.8%), Significant prostate cancer was detected in 5/14 patients (Significant PCA detection rate of 35,7%). No significant side effects were recorded. CONCLUSIONS: Our overall detection rate was 45.5% and 37.8% in Group A (patients with previous negative biopsy and persistent suspicion of PCA) and in Group B (biopsy naïve patients) respectively; clinical significant PCA detection rate was respectively 40% and 35.7%. These results are similar to current literature and promising for the future. We believe that using platforms of co-registered MRI/US fusion biopsy can potentially improve risk stratification and reduces understaging, undergrading and the need for repeat biopsies in biopsy naïve patients (using a stereotactic first mapping) and in patients with previous negative biopsy and persistent suspicion of PCA ( using a second MRI/US fusion biopsy).