Association Between Multiparametric Magnetic Resonance Imaging of the Prostate and Oncological Outcomes after Primary Treatment for Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT: The diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis has been extensively explored. Little is known about the prognostic value of mpMRI suspicion scores and other quantitative mpMRI information. OBJECTIVE: To systematically review the current literature assessing the relationship between pretreatment mpMRI and oncological outcomes after primary treatment for PCa to assess the role of mpMRI as a prognostic tool. EVIDENCE ACQUISITION: A computerized bibliographic search of MEDLINE/PubMed, EMBASE, Scopus, and the Cochrane Library CENTRAL databases was performed for all studies assessing the relationship between mpMRI and oncological outcomes after primary treatment for PCa. The review protocol is registered in the PROSPERO database (CRD42020209899). EVIDENCE SYNTHESIS: A total of six studies were included. Reliable evidence is still limited in this field. The Prostate Imaging-Reporting and Data System (PI-RADS) score was an independent predictor of biochemical recurrence (BCR) after radical prostatectomy (RP) in the majority of the studies included. The tumor volume at mpMRI was not significantly associated with BCR after RP for PCa. Data on disease progression and PCa-specific mortality are limited. Heterogeneity among the studies was substantial. CONCLUSIONS: The review shows that PI-RADS scores provide information on the future likelihood of cancer recurrence or progression, at least for men undergoing RP. We are of the view that this information should be taken into account to identify men at higher risk of unfavorable outcomes. PATIENT SUMMARY: A higher Prostate Imaging-Reporting and Data System score for magnetic resonance imaging of the prostate seems to be positively associated with oncological failure in prostate cancer and should be incorporated into future risk models

Prostate biopsy-related infection: a systematic review of risk factors, prevention strategies, and management approaches

A systematic review to identify risk factors for prostate biopsy-related infection, preventative strategies, and optimal management of infectious complications was conducted. Significant risk factors for postbiopsy infection include urogenital infection, antibiotic use, international travel, hospital exposure, bacteriuria, previous transrectal biopsy, and resistance of fecal flora to antibiotic prophylaxis (especially fluoroquinolones). Patients at risk may benefit from an adjusted biopsy protocol comprising transrectal biopsy under targeted prophylaxis, and/or the use of rectal disinfection techniques or using a transperineal approach. Management of biopsy-related infection should be based on individual risk and local resistance profiles with input from multiple specialties

High-throughput imaging assay for drug screening of 3D prostate cancer organoids

First Published June 11, 2021New treatments are required for advanced prostate cancer; however, there are fewer preclinical models of prostate cancer than other common tumor types to test candidate therapeutics. One opportunity to increase the scope of preclinical studies is to grow tissue from patient-derived xenografts (PDXs) as organoid cultures. Here we report a scalable pipeline for automated seeding, treatment and an analysis of the drug responses of prostate cancer organoids. We established organoid cultures from 5 PDXs with diverse phenotypes of prostate cancer, including castrate-sensitive and castrate-resistant disease, as well as adenocarcinoma and neuroendocrine pathology. We robotically embedded organoids in Matrigel in 384-well plates and monitored growth via brightfield microscopy before treatment with poly ADP-ribose polymerase inhibitors or a compound library. Independent readouts including metabolic activity and live-cell imaging-based features provided robust measures of organoid growth and complementary ways of assessing drug efficacy. Single organoid analyses enabled in-depth assessment of morphological differences between patients and within organoid populations and revealed that larger organoids had more striking changes in morphology and composition after drug treatment. By increasing the scale and scope of organoid experiments, this automated assay complements other patient-derived models and will expedite preclinical testing of new treatments for prostate cancer.Nicholas Choo, Susanne Ramm, Jennii Luu, Jean M. Winter, Luke A. Selth, Amy R. Dwyer … et al

Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review

Context The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed. Objective To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent. Evidence acquisition A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021. Evidence synthesis We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy. Conclusions Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers. Patient summary We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact

Guidelines of guidelines: focal therapy for prostate cancer, is it time for consensus?

Objective: To provide a summary and discussion of international guidelines, position statements and consensus statements in relation to focal therapy (FT) for prostate cancer (PCa). Methods: The European Association of Urology-European Association of Nuclear Medicine-European Society for Radiotherapy and Oncology-European Society of Urogential Radiology-International Society of Urological Pathology-International Society of Geriatric Oncology and American Urological Association-American Society for Radiation Oncology-Society of Urologic Oncology guidelines were interrogated for recommendations for FT. PubMed and Ovid Medline were searched for consensus statements. Only studies in English since 2015 were included. Reference lists of the included articles were also interrogated and a manual search for studies was also performed. Results: Our results showed a lack of long-term randomised data for FT. International Urological guidelines emphasised the need for more high-quality clinical trials with robust oncological and toxicity outcomes. Consensus and positions statements were heterogenous. Conclusion: A globally accepted guideline for FT planning, technique and follow-up are still yet to be determined. Well-designed studies with long-term follow-up and robust clinical and toxicity endpoints are needed to improve our understanding of FT and create uniform guidelines to streamline management and follow-up

Loss of SNAI2 in Prostate Cancer Correlates With Clinical Response to Androgen Deprivation Therapy

PURPOSE: Androgen receptor (AR) signaling is important in prostate cancer progression, and therapies that target this pathway have been the mainstay of treatment for advanced disease for over 70 years. Tumors eventually progress despite castration through a number of well-characterized mechanisms; however, little is known about what determines the magnitude of response to short-term pathway inhibition. METHODS: We evaluated a novel combination of AR-targeting therapies (degarelix, abiraterone, and bicalutamide) and noted that the objective patient response to therapy was highly variable. To investigate what was driving treatment resistance in poorly responding patients, as a secondary outcome we comprehensively characterized pre- and post-treatment samples using both whole-genome and RNA sequencing. RESULTS: We find that resistance following short-term treatment differs molecularly from typical progressive castration-resistant disease, associated with transcriptional reprogramming, to a transitional epithelial-to-mesenchymal transition (EMT) phenotype rather than an upregulation of AR signaling. Unexpectedly, tolerance to therapy appears to be the default state, with treatment response correlating with the prevalence of tumor cells deficient for SNAI2, a key regulator of EMT reprogramming. CONCLUSION: We show that EMT characterizes acutely resistant prostate tumors and that deletion of SNAI2, a key transcriptional regulator of EMT, correlates with clinical response