Introduction

A functional tool to optimize patient selection for magnetic resonance imaging (MRI)-guided prostate biopsy (MRGB) is an unmet clinical need. We sought to develop a prostate cancer risk calculator (PCRC-MRI) that combines MRI and clinical characteristics to aid decision-making for MRGB in North American men.

Methods

Two prospective registries containing 2354 consecutive men undergoing MRGB (September 2009 to April 2019) were analyzed. Patients were randomized into five groups, with one group randomly assigned to be the validation cohort against the other four groups as the discovery cohort. The primary outcome was detection of clinically significant prostate cancer (csPCa) defined as Gleason grade group ≥2. Variables included age, ethnicity, digital rectal exam (DRE), prior biopsy, prostate-specific antigen (PSA), prostate volume, PSA density, and MRI score. Odds ratios (OR) were calculated from multivariate logistic regression comparing two models: one with clinical variables only (clinical) against a second combining clinical variables with MRI data (clinical+MRI).

Results

csPCa was present in 942 (40%) of the 2354 men available for study. The positive and negative predictive values for csPCa in the clinical+MRI model were 57% and 89%, respectively. The area under the curve of the clinical+MRI model was superior to the clinical model in discovery (0.843 vs. 0.707, p<0.0001) and validation (0.888 vs. 0.757, p<0.0001) cohorts. Use of PCRC-MRI would have avoided approximately 16 unnecessary biopsies in every 100 men. Of all variables examined, Asian ethnicity was the most protective factor (OR 0.46, 0.29-0.75) while MRI score 5 indicated greatest risk (OR15.8, 10.5-23.9).

Conclusions

A risk calculator (PCRC-MRI), based on a large North American cohort, is shown to improve patient selection for MRGB, especially in preventing unnecessary biopsies. This tool is available at https://www.uclahealth.org/urology/prostate-cancer-riskcalculator and may help rationalize biopsy decision-making.

Objective

To investigate safety, efficacy, and quality of life impact of hemi-gland cryotherapy for clinically-significant prostate cancer (CaP), when patient selection and follow-up includes MRI-guided biopsy.

Methods

Twenty-nine men with unilateral CaP (all clinically significant with prostate volume <60 cc) were enrolled in a prospective observational trial of hemi-gland cryotherapy. Mean patient age was 68.7 years. Median prostate-specific antigen (PSA) was 6.6 ng/mL. MRI-guided biopsy (3T-MRI, Artemis US fusion) was used for diagnosis and repeated at 6-month follow-up in all men. Treatment was under general anesthesia using the BTG/Galil system. Validated questionnaires were used to determine effects of treatment on urinary and sexual function and quality of life.

Results

Cryotherapy was completed satisfactorily in all 29 cases in <60 minutes with no intraoperative complications. Significant decreases in PSA (median decrease 5.6 ng/mL) and PSA density (median decrease 0.14 ng/mL/cc) were observed (P < .01). At 6 months, 23 patients (79%) demonstrated no residual cancer on follow-up MRI-guided biopsy of the treated side. Three patients (10%) revealed micro-residual disease. Three patients (10%) had residual cancer and underwent further treatment. Ipsilateral MRI lesions were present before treatment in 26 patients and after treatment in only 2, reflecting the gross ablative effect; however, MRI showed disappearance of lesions in 4 patients with residual tumor on biopsy. The single complication was 1 case of transient urinary retention; 85% of men who were sexually active continued without change after treatment. Voiding function was unchanged.

Conclusion

Hemi-gland cryoablation for clinically-significant CaP is well-tolerated, and when patients are selected and followed by MRI/US fusion biopsy, cancer control appears promising at 6 months.

BACKGROUND: Hemiablation is a less morbid treatment alternative for appropriately selected patients with unilateral prostate cancer (PCa). However, to the authors knowledge, traditional diagnostic techniques inadequately identify appropriate candidates. In the current study, the authors quantified the accuracy for identifying hemiablation candidates using contemporary diagnostic techniques, including multiparametric magnetic resonance imaging (mpMRI) and MRI-fusion with complete systematic template biopsy. METHODS: A retrospective analysis of patients undergoing MRI and MRI-fusion prostate biopsy, including full systematic template biopsy, prior to radical prostatectomy in a single tertiary academic institution between June 2010 and February 2018 was performed. Hemiablation candidates had unilateral intermediate-risk PCa (Gleason score [GS] of 3+4 or 4+3, clinical T classification ≤T2, and prostate-specific antigen level <20 ng/dL) on MRI-fusion biopsy and 2) no contralateral highly or very highly suspicious Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) MRI lesions. Hemiablation candidates were inappropriately selected if pathologists identified contralateral GS ≥3+4 or high-risk ipsilateral PCa on prostatectomy. The authors tested a range of hemiablation inclusion criteria and performed multivariable analysis of preoperative predictors of undetected contralateral disease. RESULTS: Of 665 patients, 92 met primary hemiablation criteria. Of these 92 patients, 44 (48%) were incorrectly identified due to ipsilateral GS ≥3+4 tumors crossing the midline (21 patients), undetected distinct contralateral GS ≥3+4 tumors (20 patients), and/or ipsilateral high-risk PCa (3 patients) on prostatectomy. The rate of undetected contralateral disease ranged from 41% to 48% depending on inclusion criteria. On multivariable analysis, men with anterior index tumors were found to be 2.4 times more likely to harbor undetected contralateral GS ≥3+4 PCa compared with men with posterior lesions (P < .05). CONCLUSIONS: Clinicians and patients must weigh the risk of inadequate oncologic treatment against the functional benefits of hemiablation. Further investigation into methods for improving patient selection for hemiablation is necessary.

Purpose

The underlying premise of prostate cancer active surveillance (AS) is that cancers likely to metastasize will be recognized and eliminated before cancer-related disease can ensue. Our study was designed to determine the prostate cancer upgrading rate when biopsy guided by magnetic resonance imaging (MRGBx) is used before entry and during AS.

Materials and methods

The cohort included 519 men with low- or intermediate-risk prostate cancer who enrolled in prospective studies (NCT00949819 and NCT00102544) between February 2008 and February 2020. Subjects were preliminarily diagnosed with Gleason Grade Group (GG) 1 cancer; AS began when subsequent MRGBx confirmed GG1 or GG2. Participants underwent confirmatory MRGBx (targeted and systematic) followed by surveillance MRGBx approximately every 12 to 24 months. The primary outcome was tumor upgrading to ≥GG3.

Results

Upgrading to ≥GG3 was found in 92 men after a median followup of 4.8 years (IQR 3.1-6.5) after confirmatory MRGBx. Upgrade-free probability after 5 years was 0.85 (95% CI 0.81-0.88). Cancer detected in a magnetic resonance imaging lesion at confirmatory MRGBx increased risk of subsequent upgrading during AS (HR 2.8; 95% CI 1.3-6.0), as did presence of GG2 (HR 2.9; 95% CI 1.1-8.2) In men who upgraded ≥GG3 during AS, upgrading was detected by targeted cores only in 27%, systematic cores only in 25% and both in 47%. In 63 men undergoing prostatectomy, upgrading from MRGBx was found in only 5 (8%).

Conclusions

When AS begins and follows with MRGBx (targeted and systematic), upgrading rate (≥GG3) is greater when tumor is initially present within a magnetic resonance imaging lesion or when pathology is GG2 than when these features are absent.

Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9×10^-7 and GAB2, p = 2.0×10^-6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS-versus treatment for the initial management of patients with low-risk PC.