MRI in early detection of prostate cancer Purpose of review The use of MRI in the early detection of prostate cancer (PCa) is increasing rapidly. In the last couple of years, there have been a number of key publications that have led to its adoption in the UK and European guidelines. Recent findings PROMIS showed that standard biopsy missed up to half of clinically significant disease, compared with 5 mm template mapping biopsy. Three studies then compared the standard transrectal ultrasound (TRUS) pathway with an MRI with or without targeted biopsy pathway. These showed that MRI-targeted biopsies detect more clinically significant disease and reduce overdetection of indolent disease whilst allowing between one-third to one half of men to avoid an immediate biopsy. Cost-effectiveness data show that using MRI to determine who gets a biopsy and how that biopsy is done is a cost-neutral approach when men at lowest risk do not undergo biopsy. Summary Prostate MRI is a useful and cost-effective tool for early detection of PCa that minimizes the impact of overdetection and overtreatment whilst maximizing the detection of PCa, which could benefit from treatment. The next challenge is to ensure that centres offering MRI are able to offer high-quality MRI acquisition and reporting.

The role of prostate-specific membrane antigen PET/computed tomography in primary staging of prostate cancer Purpose of review Functional imaging with PET combined with computed tomography (CT) is of emerging interest in prostate cancer (PCa). Development of prostate-specific membrane antigen (PSMA) radiolabelled ligands has thrust PET/CT into the limelight as an alternative to conventional imaging techniques, and the evidence base to support its utility in primary staging of newly diagnosed PCa is rapidly growing. This review focuses on the most recent and important publications evaluating PSMA PET/CT in primary staging of PCa. Recent findings Three recent meta-analyses have reported 68Ga-PSMA PET/CT to demonstrate superior sensitivity and specificity for pelvic lymph node detection than conventional imaging. A recent systematic review also suggests 68Ga-PSMA PET/CT to be superior to bone scan for identifying bone metastases. However, the majority of studies are of a retrospective nature, and few provide histopathological correlation of PSMA PET/CT findings. Data from prospective studies are awaited to determine accuracy and management impact of PSMA PET/CT in primary staging. Summary PSMA PET/CT is rapidly altering the landscape of primary staging in PCa. It appears to be superior to conventional imaging for detecting regional and distant metastasis, though caution should be applied given the lack of prospective studies assessing how significant findings should be integrated into patient management. PSMA PET/CT could potentially become the gold standard for primary staging of high-risk PCa if future prospective data can prove its validity in this space.

Optimizing prostate biopsy techniques Purpose of review Prostate cancer (PCa) diagnostics have undergone a number of changes as a result of efforts to reduce the detection rate of indolent prostate cancer and to increase the hit rate for clinically significant prostate cancer (csPCa). Here, we look at those studies that have shifted our knowledge and the impact these have had on clinical practice. Recent findings The introduction of multiparametric MRI (mpMRI) and approaches to active surveillance have changed the landscape in prostate cancer diagnostics, reducing the number of men that need biopsy, but increasing the need for accuracy in mapping the extent of prostate cancer. As mpMRI reporting has become more accurate at predicting PCa, biopsy techniques have also evolved towards lesion (PI-RADS score 3–5) targeted biopsies. Uncertainty remains regarding the preferred approach to targeted biopsy, the need for systematic biopsies, and the place of software ultrasound/MRI fusion or in-bore MRI biopsy techniques versus ‘cognitive’ fusion techniques. Summary Prostate biopsies remain essential for the diagnosis of PCa. But how best to do this? Latest guidelines advocate performing both targeted and systematic biopsies. Traditionally, prostate biopsies have been performed transrectally (TRUS) with hospital readmission rates of around 3% mainly because of infection. Additionally, TRUS prostate biopsies can miss anterior prostatic lesions. The transperineal approach addresses both these issues, but has historically required general anaesthetic such that adoption for front-line diagnostics is very difficult. Recent techniques to undertake transperineal biopsy under local anaesthetic have fundamentally changed this paradigm offering the genuine possibility that in 5 years’ time, all front-line diagnostic biopsies will be performed as LATP.

Evolution of prostate cancer histopathology Purpose of review During the last 15 years several updates in the Gleason grading have been made. With the help of pertinent research results pathologists have gained a better insight into the meanings of several prostate cancer (PCa) patterns and know better how to classify them in the Gleason grade system. Recent findings During the last years PCa with cribriform architecture has be given much attention. Many data have also been published about the meaning of comedonecrosis and its relationship with Gleason pattern 4 and 5. The correlationship between comedonecrosis and intraductal PCa has also been highlighted in the recent literature. Intraductal PCa is one of the most described topics at the moment with implications to treatment such as radiation therapy. We also highlight several practical issues such as the differences of grading in prostate biopsies and prostatectomies and describe the problematic of reporting a minor high-grade pattern. Summary Many new and recent data have allowed to refine diagnosis in PCa and improve the patients's treatment. We show that comedonecrosis can be overgraded and insist on the implication with cribriform and intraducatal carcinomas. Furthermore, we describe the importance of these PCa types especially in the consideration of further treatment.

Serum and urinary biomarkers for detection and active surveillance of prostate cancer Purpose of review To provide a comprehensive review of the available biomarkers for the detection and active surveillance of prostate cancer and simplify decision-making while choosing between them. Recent findings The limitations of PSA and mpMRI and the invasive nature of prostate biopsy has led to a constant search for serum and urinary biomarkers for both the detection and monitoring during active surveillance of prostate cancer. 4K, PHI and PCA3 have been validated in prospective clinical trials for initial detection of prostate cancer and recent evidence points to potential differentiation between indolent and aggressive cancer. However, the usage in monitoring tumor dynamics is debatable because of lack of conclusive evidence. The answer to the existing problems lies in high-quality studies to establish definitive evidence and also to help choose between the plethora of biomarkers available today. Summary Despite the advancements in innovation and usage of biomarkers in prostate cancer, there exists tremendous potential in improving them to fulfil the unmet need that exists today. Studies to establish conclusive evidence and integration with imaging can tremendously aid diagnosis and monitoring.

Tissue-based genomics: which test and when Purpose of review The clinical course of localized prostate cancer varies widely, ranging from indolent disease unlikely to require treatment to aggressive cancers meriting intensive, multimodal therapy. Management recommendations have traditionally been determined based on clinical and pathologic factors, including serum prostate - specific antigen (PSA), clinical stage, and Gleason score. Unfortunately, these factors have limited ability to describe the underlying biology of a given tumor. Tissue-based genomic tests have emerged as a promising tool to more accurately characterize prostate cancer biology and projected clinical course. The current review article summarizes available data describing the clinical use of genomic assays, with a specific focus on three critical scenarios. Recent findings We reviewed the potential role of tissue-based genomic assays in determining: the appropriateness of active surveillance versus definitive therapy, patients that will benefit from adjuvant radiation therapy following radical prostatectomy, and men most likely to benefit from concurrent androgen deprivation therapy with primary radiotherapy. Summary Current literature suggests that commercially available genomic tests provide prognostic information independent of traditional risk factors that may augment clinical decision-making. Additional data will better clarify the optimal use of each test across common clinical scenarios.

Active surveillance for intermediate-risk prostate cancer: yes, but for whom? Purpose of review Active surveillance is becoming more widely accepted as an initial management option for carefully selected men with favorable intermediate-risk prostate cancer (PCa). As prospective active surveillance cohorts mature sufficiently to begin evaluating longer-term outcomes, consensus on more precise evidence-based guidelines is needed to identify the patient cohorts who may be safely managed with active surveillance and what the ideal surveillance protocol entails. Recent findings Long-term outcomes updates have suggested a trend toward worse 15-year survival outcomes for intermediate-risk patients on active surveillance compared with definitive treatment, but ‘intermediate-risk’ is a broad category and there is a subset of favorable intermediate-risk patients for whom survival outcomes remain equivalent. Promising updates to current risk stratification include consideration of genomic classifiers, advanced imaging and more nuanced interpretation of biopsy results. Summary Despite widespread acknowledgement of the pitfalls of overtreatment in clinically localized PCa, utilization of active surveillance in the intermediate-risk population remains marginal, in part due to the absence of easily interpretable consensus recommendations. As more long-term outcomes data become available for this subgroup, the field is now poised to refine the definition of favorable intermediate-risk patients for whom active surveillance is a safe, evidence-based first-line management option.

Risk stratification and avoiding overtreatment in localized prostate cancer Purpose of review Significant morbidity is associated with overtreatment of clinically localized prostate cancer (PCa). Risk stratification tools such as novel biomarkers, MRI and risk calculators are useful in predicting which patients would benefit from active surveillance. This review examines current risk stratification tools in localized PCa and the safety of active surveillance in these patients. Recent findings Very low risk, low-risk and favourable intermediate-risk PCa variants may benefit from treatment with active surveillance. These disease categories have been shown (with up to 10-year follow-up) to have survival and cancer-specific complication rates similar to immediate definitive treatment. Novel biomarkers sensitively predict upstaging, recurrence and metastatic progression while multiparametric MRI reliably detects clinically significant PCa and is valuable in the biopsy naïve patient considering active surveillance. Lastly, risk calculators and nomograms are being developed to combine clinical data and provide optimal individualized treatment while minimizing overtreatment in clinically localized disease. Summary Although large randomized trials are needed to validate treatment pathways, current data supports active surveillance in certain clinically localized PCa. Many tools exist to define and support active surveillance in this group.

Prostate radiotherapy in newly diagnosed metastatic prostate cancer Purpose of review The aim of this article is to review the role of prostate radiotherapy in the multimodal management of newly diagnosed metastatic hormone naïve prostate cancer. Recent findings Two randomized controlled trials have evaluated the role of prostate radiotherapy with systemic therapy (androgen deprivation therapy ± docetaxel) in newly diagnosed metastatic hormone-naive prostate cancer. In a combined cohort of over 2000 patients, prostate radiotherapy with systemic therapy improved survival over systemic therapy alone in patients with low metastatic burden but not in high-burden patients. Prostate radiotherapy with systemic therapy is now a recommended first-line option for newly diagnosed men with low metastatic burden prostate cancer. The current recommended definition for low metastatic burden is based on conventional imaging (99mTc bone scans and CT/MRI). Cross-correlative studies are required to pick an appropriate threshold for sensitive-imaging modalities such as PSMA PET or whole-body MRI. Ongoing trials are evaluating prostate radiotherapy in this setting combined with abiraterone/docetaxel and metastasis-directed therapy. Summary Prostate radiotherapy with systemic therapy improves survival in patients with newly diagnosed, low metastatic burden prostate cancer and is a recommended first-line treatment option. Ongoing trials are evaluating combination with metastasis-directed therapy and other systemic treatments.