Context Although prostate cancer (PCa) screening reduces the incidence of advanced disease and mortality, trade-offs include overdiagnosis and resultant overtreatment. Objective To review primary data on PCa overdiagnosis and overtreatment. Evidence acquisition Electronic searches were conducted in Cochrane Central Register of Controlled Trials, PubMed, and Embase from inception to July 2013 for original articles on PCa overdiagnosis and overtreatment. Supplemental articles were identified through hand searches. Evidence synthesis The lead-time and excess-incidence approaches are the main ways used to estimate overdiagnosis in epidemiological studies, with estimates varying widely. The estimated number of PCa cases needed to be diagnosed to save a life has ranged from 48 down to 5 with increasing follow-up. In clinical studies, generally lower rates of overdiagnosis have been reported based on the frequency of low-grade minimal tumors at radical prostatectomy (1.7–46.8%). Autopsy studies have reported PCa in 18.5–38.5%, although not all are low grade or low volume. Factors influencing overdiagnosis include the study population, screening protocol, and background incidence, limiting generalizability between settings. Reported rates of overtreatment vary widely in the literature, although contemporary international studies suggest increasing use of conservative management. Conclusions Epidemiological, clinical, and autopsy studies have been used to examine PCa overdiagnosis, with estimates ranging widely from 1.7% to 67%. Correspondingly, estimates of overtreatment vary widely based on patient features and may be declining internationally. Careful patient selection for screening and reducing overtreatment are important to preserve the benefits and reduce the downstream harms of prostate-specific antigen testing. Because all of these estimates are extremely population and context specific, this must be considered when using these data to inform policy. Patient summary Screening reduces spread and death from prostate cancer (PCa) but overdiagnoses some low-risk tumors that may not have caused harm. Because treatment has potential side effects, it is critical that not all patients with PCa receive aggressive treatment.

Patients sustaining a pelvic fracture with GUI have an increase in morbidity. Although GUI was not an independent predictor of mortality, patients who sustained a pelvic fracture with GUI had a greater number of concomitant injuries resulting in an increase in overall mortality compared with those without an associated GUI.

Purpose An optimal prostate biopsy in clinical practice is based on a balance between adequate detection of clinically significant prostate cancers (sensitivity), assuredness regarding the accuracy of negative sampling (negative predictive value [NPV]), limited detection of clinically insignificant cancers, and good concordance with whole-gland surgical pathology results to allow accurate risk stratification and disease localization for treatment selection. Inherent within this optimization is variation of the core number, location, labeling, and processing for pathologic evaluation. To date, there is no consensus in this regard. The purpose of this review is 3-fold: 1. To define the optimal number and location of biopsy cores during primary prostate biopsy among men with suspected prostate cancer, 2. To define the optimal method of labeling prostate biopsy cores for pathologic processing that will provide relevant and necessary clinical information for all potential clinical scenarios, and 3. To determine the maximal number of prostate biopsy cores allowable within a specimen jar that would not preclude accurate histologic evaluation of the tissue. Materials and Methods A bibliographic search covering the period up to July, 2012 was conducted using PubMed®. This search yielded approximately 550 articles. Articles were reviewed and categorized based on which of the three objectives of this review was addressed. Data was extracted, analyzed, and summarized. Recommendations based on this literature review and our clinical experience is provided. Results The use of 10–12-core extended-sampling protocols increases cancer detection rates (CDRs) compared to traditional sextant sampling methods and reduces the likelihood that patients will require a repeat biopsy by increasing NPV, ultimately allowing more accurate risk stratification without increasing the likelihood of detecting insignificant cancers. As the number of cores increases above 12 cores, the increase in diagnostic yield becomes marginal. Only limited evidence supports the use of initial biopsy schemes involving more than 12 cores or saturation. Apical and laterally directed sampling of the peripheral zone increases CDR, reduces the need for repeat biopsies, and predicts pathological features on prostatectomy while transition-zone biopsies do not. There is little data to suggest that knowing the exact site of an individual positive biopsy core provides meaningful clinical information. However, determining laterality of cancer on biopsy may be helpful for both predicting sites of extracapsular extension and therapeutic planning. Placement of multiple biopsy cores in a single container (>2) appears to compromise pathologic evaluation, which can reduce CDR and increase the likelihood of equivocal diagnoses. Conclusions A 12-core systematic biopsy that incorporates apical and far-lateral cores in the template distribution allows maximal cancer detection, avoidance of a repeat biopsy, and adequate information for both identifying men who need therapy and...

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BACKGROUND Increasing evidence supports the use of MRI-ultrasound fusion-targeted prostate biopsy (MRF-TB) to improve the detection of clinically significant prostate cancer (PCa) while limiting detection of indolent disease compared to systematic 12-core biopsy (SB). OBJECTIVE We report results of MRF-TB and SB and the relationship between biopsy outcomes and pre-biopsy MRI in 601 men presenting to our center. DESIGN/SETTING/PARTICIPANTS Retrospective analysis of a prospectively acquired cohort of men presenting for prostate biopsy over a 26-month period. A total of 601 of 803 consecutively eligible men were included. INTERVENTIONS All men were offered pre-biopsy MRI and assigned a maximum MRI suspicion score (mSS). Men with an MRI abnormality underwent combined MRF-TB and SB. OUTCOMES Detection rate of all PCa and high-grade PCa (Gleason score (GS)≥7) were compared by McNemar's test. RESULTS MRF-TB detected fewer GS6 PCa (75 vs 121, p<0.001) and more GS≥7 PCa (158 vs 117, p<0.001) than SB. Increasing mSS was associated with increasing detection of GS≥7 PCa (p<0.001), but had no relationship to the detection of GS6 PCa. The prediction of GS≥7 disease by mSS varied according to biopsy history. Compared to SB, MRF-TB identified more GS≥7 cancer in men with no prior biopsy (88 vs 72, p=0.012), with prior negative biopsy (28 vs 16, p=0.010), and with prior cancer diagnosis (42 vs 29, p=0.043). MRF-TB detected fewer GS6 cancers in men with no prior biopsy (32 vs 60, p<.001) and prior cancer (30 vs 46, p=0.034). Limitations include retrospective design and potential for selection bias given a referral population. CONCLUSIONS MRI-US fusion-targeted biopsy detects more high-grade cancer than systematic biopsy while limiting detection of GS6 cancer in men presenting for prostate biopsy. These findings suggest that pre-biopsy mpMRI and MRF-TB should be considered in all men undergoing prostate biopsy and, in conjunction with biopsy indication, mSS may ultimately help identify a select group of men at low risk of high-grade cancer in whom prostate biopsy may not be warranted.

Purpose Optimization of prostate biopsy requires addressing the shortcomings of standard systematic transrectal ultrasound guided biopsy, including false-negative rates, incorrect risk stratification, detection of clinically insignificant disease and the need for repeat biopsy. Magnetic resonance imaging is an evolving noninvasive imaging modality that increases the accurate localization of prostate cancer at the time of biopsy, and thereby enhances clinical risk assessment and improves the ability to appropriately counsel patients regarding therapy. In this review we 1) summarize the various sequences that comprise a prostate multiparametric magnetic resonance imaging examination along with its performance characteristics in cancer detection, localization and reporting standards; 2) evaluate potential applications of magnetic resonance imaging targeting in prostate biopsy among men with no previous biopsy, a negative previous biopsy and those with low stage cancer; and 3) describe the techniques of magnetic resonance imaging targeted biopsy and comparative study outcomes. Materials and Methods A bibliographic search covering the period up to October 2013 was conducted using MEDLINE®/PubMed®. Articles were reviewed and categorized based on which of the 3 objectives of this review was addressed. Data were extracted, analyzed and summarized. Results Multiparametric magnetic resonance imaging consists of anatomical T2-weighted imaging coupled with at least 2 functional imaging techniques. It has demonstrated improved prostate cancer detection sensitivity up to 80% in the peripheral zone and 81% in the transition zone. A prostate cancer magnetic resonance imaging suspicion score has been developed, and is depicted using the Likert or PI-RADS (Prostate Imaging Reporting and Data System) scale for better standardization of magnetic resonance imaging interpretation and reporting. Among men with no previous biopsy, magnetic resonance imaging increases the frequency of significant cancer detection to 50% in low risk and 71% in high risk patients. In low risk men the negative predictive value of a combination of negative magnetic resonance imaging with prostate volume parameters is nearly 98%, suggesting a potential role in avoiding biopsy and reducing over detection/overtreatment. Among men with a previous negative biopsy 72% to 87% of cancers detected by magnetic resonance imaging guidance are clinically significant. Among men with a known low risk cancer, repeat biopsy using magnetic resonance targeting demonstrates a high likelihood of confirming low risk disease in low suspicion score lesions and of upgrading in high suspicion score lesions. Techniques of magnetic resonance imaging targeted biopsy include visual estimation transrectal ultrasound guided biopsy; software co-registered magnetic resonance imaging-ultrasound, transrectal ultrasound guided biopsy; and in-bore magnetic resonance imaging guided biopsy. Although the improvement in accuracy and efficiency of visual estimation biopsy compared to systematic...

PURPOSE To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer. METHODS Patients with clinical T2-4aN0/XM0 muscle-invasive bladder cancer eligible for RC were enrolled. The initial six patients received lead-in pembrolizumab 200 mg once 2 weeks prior to pembrolizumab 200 mg once on day 1, cisplatin 70 mg/m2 once on day 1, and gemcitabine 1,000 mg/m2 once on days 1 and 8 every 21 days for four cycles. This schedule was discontinued for toxicity and subsequent patients received cisplatin 35 mg/m2 once on days 1 and 8 without lead-in pembrolizumab. The primary end point was pathologic downstaging (< pT2N0) with null and alternative hypothesis rates of 35% and 55%, respectively. Secondary end points were toxicity including patient-reported outcomes, complete pathologic response (pT0N0), event-free survival, and overall survival. Association of pathologic downstaging with programmed cell death ligand 1 staining was explored. RESULTS Thirty-nine patients were enrolled between June 2016 and March 2020 (72% cT2, 23% cT3, and 5% cT4a). Patients received a median of four cycles of therapy. All patients underwent RC except one who declined. Twenty-two of 39 patients (56% [95% CI, 40 to 72]) achieved < pT2N0 and 14 of 39 (36% [95% CI, 21 to 53]) achieved pT0N0. Most common adverse events (AEs) of any grade were thrombocytopenia (74%), anemia (69%), neutropenia (67%), and hypomagnesemia (67%). One patient had new-onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Clinicians consistently under-reported AEs when compared with patients. CONCLUSION Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe. A global study of perioperative chemotherapy plus pembrolizumab or placebo is ongoing.

A negative prebiopsy mpMRI confers an overall NPV of 82% on 12-core biopsy for all cancer and 98% for GS ≥7 cancer. Based on biopsy indication, these findings assist in prebiopsy risk stratification for detection of high-risk disease and may provide guidance in the decision to pursue biopsy.