A prostate biopsy risk calculator based on MRI: development and comparison of the Prospective Loyola University multiparametric MRI (PLUM) and Prostate Biopsy Collaborative Group (PBCG) risk calculators.

OBJECTIVES: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC. PATIENTS AND METHODS: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts. RESULTS: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05). CONCLUSIONS: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa.

Risk of prostate cancer for men with prior negative biopsies undergoing magnetic resonance imaging compared with biopsy-naive men: A prospective evaluation of the PLUM cohort.

BACKGROUND: Men with prior negative prostate biopsies have a lower risk of being diagnosed with prostate cancer in comparison with biopsy-naive men. However, the relative clinical utility of identified lesions on multiparametric magnetic resonance imaging (mpMRI) is uncertain between the 2 settings. METHODS: Patients from the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (January 2015 to June 2020) were examined. The detection of any prostate cancer and clinically significant prostate cancer (Gleason score ≥ 3 + 4) was stratified by Prostate Imaging-Reporting and Data System (PI-RADS) scores in the prior negative and biopsy-naive settings. Multivariable logistic regression models (PLUM models) assessed predictors, and decision curve analyses were used to estimate the clinical utility of PI-RADS cutoffs relative to the models. RESULTS: Nine hundred men (420 prior negative patients and 480 biopsy-naive patients) were included. Prior negative patients had lower risks of any prostate cancer (27.9% vs 54.4%) and clinically significant prostate cancer (20.0% vs 38.3%) in comparison with biopsy-naive patients, and this persisted when they were stratified by PI-RADS (eg, PI-RADS 3: 13.6% vs 27.4% [any prostate cancer] and 5.2% vs 15.4% [clinically significant prostate cancer]). The rate of detection of clinically significant prostate cancer was 5.3% among men with prior negative biopsy and PI-RADS ≤ 3. Family history and Asian ancestry were significant predictors among biopsy-naive patients. PLUM models demonstrated a greater net benefit and reduction in biopsies (45.8%) without missing clinically significant cancer in comparison with PI-RADS cutoffs (PI-RADS 4: 34.0%). CONCLUSIONS: Patients with prior negative biopsies had lower prostate cancer detection by PI-RADS score category in comparison with biopsy-naive men. Decision curve analyses suggested that many biopsies could be avoided by the use of the PLUM models or a PI-RADS 4 cutoff without any clinically significant cancer being missed. LAY SUMMARY: Men with a prior negative prostate biopsy had a lower risk of harboring prostate cancer in comparison with those who never had a biopsy. This was true even when patients in each group had similar multiparametric magnetic resonance imaging (mpMRI) findings in terms of Prostate Imaging-Reporting and Data System (PI-RADS)-graded lesions. Decision curve analyses showed that many biopsies could be avoided by the use of the Prospective Loyola University mpMRI prediction models or a PI-RADS 4 cutoff for patients with prior negative biopsies.

Low suspicion lesions on multiparametric magnetic resonance imaging predict for the absence of high-risk prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? Over-treatment of indolent prostate cancer lesions is a problem which can result in increased human and medical costs. Lesions with a low suspician level at mpMRI of the prostate have low risk of including high risk prostate cancer. OBJECTIVE: To determine whether multiparametric magnetic resonance imaging (mpMRI) has the potential to identify patients at low risk for cancer, thus obviating the need for biopsy. Prostate cancer is currently diagnosed by random biopsies, resulting in the discovery of multiple low-risk cancers that often lead to overtreatment. PATIENTS AND METHODS: We reviewed 800 consecutive patients who underwent a 3 Tesla mpMRI of the prostate with an endorectal coil from March 2007 to November 2011. All suspicious lesions were independently reviewed by two radiologists using T2-weighted, diffusion-weighted, spectroscopic and dynamic contrast-enhanced MRI sequences. Patients with only low suspicion lesions (maximum of two positive parameters on mpMRI) who subsequently underwent transrectal ultrasonography (TRUS)/MRI fusion targeted biopsy were selected for analysis. RESULTS: In total, 125 patients with only low suspicion prostatic lesions on mpMRI were identified. On TRUS/MRI fusion biopsy, 77 (62%) of these patients had no cancer detected, 38 patients had Gleason 6 disease and 10 patients had Gleason 7 (3+4) disease. There were 30 patients with cancer detected on biopsy who qualified for active surveillance using 2011 National Comprehensive Cancer Network guidelines. No cases of high-risk (≥ Gleason 4+3) cancer were identified on biopsy and, of the fifteen patients who underwent radical prostatectomy at our institution, none were pathologically upgraded to high-risk cancer. Thus, for patients with only low suspicion lesions, 107 (88%) patients either had no cancer or clinically insignificant disease. CONCLUSIONS: The results obtained in the present study show that low suspicion lesions on mpMRI are associated with either negative biopsies or low-grade tumours suitable for active surveillance. Such patients have a low risk of harbouring high-risk prostate cancers.

Targeted therapeutic strategies for the management of renal cell carcinoma.

PURPOSE OF REVIEW: This article reviews recent developments in the use of systemic targeted therapies for the treatment of advanced clear and nonclear cell renal cell carcinoma (RCC). The genetic/molecular basis of each form of RCC is discussed and current treatments and clinical trials are described. RECENT FINDINGS: The treatment of advanced RCC continues to be a major challenge for uro-oncologists. The rapid growth in therapeutic options has brought much needed improvements in overall and progression-free survival, although durable complete responses remain elusive. The recent identification of mutations in genes involved in chromatin remodeling will likely lead to the investigation of whether components of this critical process can also be valid therapeutic targets in clear cell RCC. Similarly, efforts to decipher the molecular mechanisms underlying nonclear cell variants of RCC are beginning to engender novel therapeutic strategies directed against these rarer forms of kidney cancer. Despite the availability of multiple treatment options, several challenges remain: selecting the best first-line or subsequent therapy for a given patient, the optimal sequencing of the various agents available, designing trials with appropriate comparison arms and endpoints, and identifying well tolerated and effective drug combinations. SUMMARY: Agents targeting the vascular endothelial growth factor and mammalian target of rapamycin pathways remain the mainstay in the management of metastatic RCC. Ongoing and future studies are expected to facilitate the development of therapeutic regimens that incorporate agents with improved tolerability and enhanced efficacy by continuing to capitalize on the strides made by basic and translational scientists in uncovering the mechanisms underlying the various forms of RCC.