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OBJECTIVE: To review the recent milestones in MRI and PET based imaging and evaluate their evolving role in the setting of elevated PSA as well as localized prostate cancer. BACKGROUND: The importance of multiparametric MRI (mpMRI) and PET based imaging for the diagnosis and staging of prostate cancer cannot be understated. Accurate staging has become another significant milestone with the use of PET scans, particularly with prostate specific radiotracers like 68-Gallium Prostate Specific Membrane Antigen (68Ga-PSMA). Integrated PET/MRI systems are commercially available and can be modulated to evaluate the unique needs of localized as well as recurrent prostate cancer. METHODS: A literature search was performed using PubMed and Google Scholar using the MeSH compliant and other keywords that included prostate cancer, PSA, mpMRI, PET CT, PET/MRI. CONCLUSIONS: mpMRI has now established itself as the gold-standard of local prostate imaging and has been incorporated into international guidelines as part of the diagnostic work-up of prostate cancer. PSMA PET/CT has shown superiority over conventional imaging even in staging of localized prostate cancer based on recent randomized control data. Imaging parameters from PET/MRI have been shown to be associated with malignancy, Gleason score and tumour volume. As mpMRI and PSMA PET/CT become more ubiquitous and established; we can anticipate more high-quality data, cost optimization and increasing availability of PET/MRI to be ready for primetime in localized prostate cancer.

The definition of oligometastatic prostate cancer (OMPC) includes a heterogenous group of disease states, mostly defined by the number and site of metastases, which seems to be biologically different to widespread tumors. Evidence suggests a substantial survival benefit for this subgroup of limited metastatic burden which is currently seen as a potentially curable disease and therefore with an increasing interest in the scientific community. As there is still no consensus on the definition of OMPC, commonly used criteria are based on the CHAARTED and LATITUDE trials. The management algorithms for these patients were rapidly changing in the past decade due to recent data with a paradigm shift to a multimodal intensification of the treatment by the availability of combinations of hormonal therapy with taxane-based chemotherapy and androgen-receptor-targeted agents leading to significant improvement of clinical outcomes. In addition, radiotherapy of the primary tumor is associated with significant survival benefit in patients with OMPC establishing a new arm in the multimodal treatment concept. Recent data on metastases directed therapy and cytoreductive prostatectomy showed promising results, while there is still a lack of prospective trials and therefore should be limited to experimental settings. The purpose of this review is to summarize and discuss the existing data on treatment of OMPC.

Despite innovations in surgical technology and advancements in radiation therapy, radical treatments for clinically localized prostate cancer are associated with significant patient morbidity, including both urinary and sexual dysfunction. This has created a vital need for therapies and management strategies that provide an acceptable degree of oncologic efficacy while mitigating these undesirable side effects. Successful developments in screening approaches and advances in prostate imaging have allowed clinicians to identify, localize, and more precisely target early cancers. This has afforded urologists with an important opportunity to develop and employ focal ablation techniques that selectively destroy tumors while preserving the remainder of the gland, thus avoiding detrimental treatment effects to surrounding sensitive structures. A lack of high-level evidence supporting such an approach had previously hindered widespread adoption of focal treatments, but there are now numerous published clinical trials which have sought to establish benchmarks for safety and efficacy. As the clinical evidence supporting a potential role in prostate cancer treatment begins to accumulate, there has been a growing acceptance of focal therapy in the urologic oncology community. In this narrative review article, we describe the techniques, advantages, and side effect profiles of the most commonly utilized focal ablative techniques and analyze published clinical trial data supporting their evolving role in the prostate cancer treatment paradigm.

Combined molecular and morphologic imaging modalities have emerged in recent years as an alternative to conventional imaging in prostate cancer (PC). In particular, novel prostate-specific membrane antigen (PSMA) radiotracers have demonstrated increased sensitivity and specificity for the initial staging of men with clinically localized PC, as well as for PC detection in the setting of biochemical recurrence (BCR). Molecular imaging is increasingly used to guide treatment decisions in these patients-though its impact on survival has yet to be established. Improved PC detection in men with BCR has also helped to identify a subset of patients with oligometastatic disease. The optimal management of oligometastatic PC and the role of metastasis-directed therapies (MDT) are the subjects of ongoing studies. In comparison to clinically localized or biochemically recurrent PC, the role of molecular imaging in men with advanced disease is less established. In metastatic castration-resistant PC (mCRPC), PSMA-based imaging has primarily been investigated as a companion diagnostic tool to predict and monitor response to PSMA-targeted radioligand therapy (RLT). More recent efforts have focused on using molecular imaging to monitor treatment response to conventional chemohormonal therapies. However, despite promising early results, several barriers remain to the widespread use of PSMA-based imaging in metastatic PC: temporary flares in PSMA uptake have been described in a subset of patients after initiation of therapy, and the underlying mechanism and clinical implications of this phenomenon are still poorly understood. Furthermore, whereas PSMA is invariably expressed in hormone-sensitive PC, loss of PSMA expression is increasingly recognized in a subset of mCRPC patients with aggressive disease. Although this may limit the use of PSMA-based imaging as a standalone modality in advanced PC, loss of PSMA uptake may also provide non-invasive and clinically relevant molecular insight on patients' underlying tumor biology.

Use of serum prostate-specific antigen (PSA) testing for early detection of prostate cancer appears to reduce cancer-specific mortality. Due to the limited specificity of PSA for clinically significant [Grade Group (GG) ≥2] cancer, however, screening carries substantial risks, including frequent unnecessary prostate biopsies and overdetection of non-aggressive cancers. To that end, serum and urine biomarkers with improved specificity for GG ≥2 cancer have been proposed for clinical use following PSA. In the current article, we present clinical validation data for five such biomarkers: PHI, 4Kscore, SelectMDx, ExoDx, and MPS. For all studies, we specify the study population (overall biopsy referral vs. pre-specified PSA ranges), previous biopsy status (biopsy-naive vs. previous negative biopsy), and the proportion of subjects diagnosed with GG ≥2 cancer. Outcomes include test performance characteristics: sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Published data were used to compute the number of unnecessary biopsies avoided and number of GG ≥2 cancers missed if the biomarker had been used clinically to select for prostate biopsy. The evidence review is preceded by a primer on these and other clinically-relevant summary statistics.

Epigenetic alterations, including changes in DNA methylation, histone modifications and nucleosome remodeling, result in abnormal gene expression patterns that contribute to prostate tumor initiation and continue to evolve during the course of disease progression. Epigenetic modifications are responsible for silencing tumor-suppressor genes, activating oncogenic drivers, and driving therapy resistance and thus have emerged as promising targets for antineoplastic therapy in prostate cancer. In this review, we discuss the role of epigenetics in prostate cancer with a particular emphasis on clinical implications. We review how epigenetic regulators crosstalk with critical biological pathways, including androgen receptor signaling, and how these interactions dynamically control prostate cancer transcriptional profiles. Because of their potentially reversible nature, restoration of a "normal" epigenome could provide a basis for innovative therapeutic strategies in prostate cancer. We highlight how particular epigenetic alterations are emerging as potential diagnostic and prognostic biomarkers and/or targets for the treatment of advanced prostate cancer.

In 2016, the NIH designated sexual and gender minorities (SGM) a health disparity population. The next year, the American Society of Clinical Oncology highlighted the need to improve the suboptimal cancer and survivorship care received by SGM populations. There are currently no evidence-based training programs in culturally competent care of prostate cancer patients who are gay, bisexual and/or transgender. In this selective review, we summarize findings from the largest quantitative studies focused on sexual minority prostate cancer survivors and from 65 interviews with NIH staff, clinicians, and cancer clinics in 11 US cities. The report is divided into three parts and uses a question and answer format to address 21 questions relevant to clinicians providing care to SGM prostate cancer patients. First, we identify population-specific issues that are culturally relevant in the care of SGM patients with prostate cancer. While a body of research has emerged on sexual minority prostate cancer patients, the literature on gender minorities is limited to single case reports and inadequate to inform practice. This review covers definitions, population size, cultural and historical context, sexual behavior, population invisibility, sexual orientation and gender identity (SOGI) in the electronic medical record, disparities and evidence of discrimination in treatment provision. The second part focuses on promoting evidence-informed, patient-centered care. This includes current practices in assessing sexual orientation, management of disclosure of sexual orientation, how to address common problems sexual minority men experience post-treatment, common questions sexual minority patients have, management of urinary incontinence, HIV and STI risk during and post-treatment, and sub-groups of sexual minority patients with worse outcomes. It then identifies how male partners differ in prostate cancer support, current research on rehabilitation for sexual minority men, issues in advanced prostate cancer, and things to avoid with minority patients. Finally, we examine the cultural divide between provider and patient, advocating for cultural humility when working with minority patients. Training programs and continuing education can help providers both to become more aware of their own cultural assumptions, informed about health disparities, and able to provide quality care, and to make clinics more welcoming to SGM patients.

Prostate cancer is a significant public health burden and one of the most common cancers globally and in the United States. The current cornerstone of prostate cancer systemic treatment involves the suppression of androgen receptor (AR) signaling, either by reducing the body's testosterone production or inhibiting its binding to AR and its subsequent gene regulatory network driving carcinogenesis. This signaling pathway plays a central role in both hormone sensitive and castration resistant prostate cancer (CRPC), as evidenced by survival benefit when AR-targeted therapies are applied in the setting of CRPC. With the development of increasingly potent central and peripherally acting androgen targeting agents physicians treating prostate cancer can expect to treat their patients for a longer duration with a larger selection of effective agents. In this setting clinicians are now faced with questions of how to best tailor treatments for the prostate cancer patient to not only maximize overall survival but also optimize the quality of life and mitigate toxicity. In this manuscript we discuss the newer hormone therapy agents for prostate cancer and highlight what they indicate about optimizing medical castration, and the potential value of peripheral blockade.

Pelvic nodal involvement is present in 13% of new prostate cancer diagnoses each year and is associated with a poor prognosis compared to localized disease. Grouped as stage IV along with distant metastatic disease, node-positive nonmetastatic patients historically received systemic therapy alone as primary treatment. This treatment paradigm has shifted as data have demonstrated that these patients may benefit from aggressive locoregional therapy and are potentially curable. There is currently a lack of randomized evidence to define the optimal management for node-positive patients. While a few trials have included node-positive patients, the majority of data are derived from large multi-institutional series or population-based series. This narrative review summarizes the current literature supporting curative-intent management strategies for patients diagnosed with nonmetastatic clinically node-positive prostate cancer (cN1M0), as well as patients found to have pathologic nodal disease at the time of surgery (pN1M0). Treatment of both scenarios requires multimodality considerations including surgery, radiation therapy (RT) and systemic therapy to minimize the risks of both locoregional and distant recurrence. Future considerations include developments in enhanced imaging and systemic therapy. Inclusion of node-positive patients on prospective, randomized trials such as NRG GU 008 is needed to enhance our understanding of optimal management strategies.