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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.

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.

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.