Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer?

The treatment landscape for metastatic hormone-sensitive prostate cancer continues to evolve, with systemic treatment being the mainstay of current treatment. Prognostic and predictive factors such as tumour volume and disease presentation have been studied to assess responses to different treatments. Intensification and de-escalation strategies arouse great interest, so several trials are being developed to further personalize the therapy in these populations. Is there an optimal sequence and a possible option to de-intensify treatment in selected patients with a favourable profile? This and other goals will be the subject of this review.

Docetaxel Provides Oncological Benefits in the Era of New-Generation Androgen Receptor Inhibitors - or Is Three a Crowd?

In recent years, several systemic therapies have been introduced for metastatic hormone-sensitive prostate cancer, including androgen deprivation therapy (ADT) combined with docetaxel (Doc) and/or new-generation androgen receptor signaling inhibitors (ARSI). Trials evaluating ADT + ARSI have consistently demonstrated an overall survival (OS) benefit for doublet therapy over ADT alone. Similarly, the STOPCaP meta-analysis showed an OS benefit in favor of ADT + Doc versus ADT alone. ARSI, Doc, and ADT have different antitumor mechanisms, thus potentiating the effect of combination therapy. Two randomized trials showed that the addition of ARSI to ADT + Doc improves OS, especially for synchronous high-volume disease. However, the real question about triplet therapy remains unanswered: whether combining Doc with ARSI improves outcomes compared to ADT + ARSI. As there are no head-to-head comparisons, this narrative review aims to summarize the current evidence regarding triplet therapy versus doublet therapy including ADT+ ARSI.

Role of Radiotherapy and Hormone Therapy in Patients with Node-Positive Locally Advanced Prostate Cancer

New-generation imaging techniques and the increasing use of surgery in high-risk prostate cancer (PCa) allow usto detect many cases of nodal disease at initial diagnosis or after resection. The treatment of PCa with pathologic regional nodeshas evolved from the exclusive use of systemic therapy to its combination with locoregional treatment. It can also represent abenefit in the overall survival. However, the evidence from randomised studies is limited. Thus, we review the most relevantresults in this scenario.Materials and Methods: A literature search was conducted in MEDLINE, PubMed, EMBASE, Clinical-Trials.gov and Webof Science on January 2023 to review node-positive PCa by considering the relevant literature on this topic published with norestrictions on date and language. The search keywords used were “Prostatic Neoplasms” (MeSh) and “Node-positive” (TextWord) and “Radiotherapy” (MeSh) and (“Androgen Antagonists” (MeSh) or “Antineoplastic Agents, Hormonal” (MeSh)), whichare indexed within the Medical Subject Headings database.Results: The management of node-positive PCa has no clear definitive consensus at the initial disease diagnosis or after surgery.However, in this review, we summarise the existing literature for the management of these patients in both scenarios, consideringimaging tests, radiotherapy, hormone therapy and second-generation hormonal treatments.Conclusions: The combination of radiotherapy and androgen-deprivation therapy is the treatment of choice. The addition ofsecond-generation hormone therapy, plus the intensification of radiotherapy schedules, will likely change the treatment paradigm for these patients. (AU)

Novel Approaches in the Systemic Management of High-Risk Prostate Cancer.

Locally advanced prostate cancer comprises approximately 20% of new prostate cancer diagnoses. For these patients, international guidelines recommend treatment with radiotherapy (RT) to the prostate in combination with long-term (2-3 years) androgen deprivation therapy (ADT), or radical prostatectomy in combination with extended pelvic lymph node dissection (PLND) as another treatment option for selected patients as part of multimodal therapy. Improvements in overall survival with docetaxel or an androgen receptor signaling inhibitor have been achieved in patients with metastatic castration sensitive or castration resistant prostate cancer. However, the role of systemic therapy combinations for high risk and/or unfavorable prostate cancer is unclear. In this context, the aim of this review is to assess the current evidence for systemic treatment combinations as part of primary definitive therapy in patients with high-risk localized prostate cancer.

Role of Radiotherapy and Hormone Therapy in Patients with Node-Positive Locally Advanced Prostate Cancer.

BACKGROUND: New-generation imaging techniques and the increasing use of surgery in high-risk prostate cancer (PCa) allow us to detect many cases of nodal disease at initial diagnosis or after resection. The treatment of PCa with pathologic regional nodes has evolved from the exclusive use of systemic therapy to its combination with locoregional treatment. It can also represent a benefit in the overall survival. However, the evidence from randomised studies is limited. Thus, we review the most relevant results in this scenario. MATERIALS AND METHODS: A literature search was conducted in MEDLINE, PubMed, EMBASE, Clinical-Trials.gov and Web of Science on January 2023 to review node-positive PCa by considering the relevant literature on this topic published with no restrictions on date and language. The search keywords used were "Prostatic Neoplasms" (MeSh) and "Node-positive" (Text Word) and "Radiotherapy" (MeSh) and ("Androgen Antagonists" (MeSh) or "Antineoplastic Agents, Hormonal" (MeSh)), which are indexed within the Medical Subject Headings database. RESULTS: The management of node-positive PCa has no clear definitive consensus at the initial disease diagnosis or after surgery. However, in this review, we summarise the existing literature for the management of these patients in both scenarios, considering imaging tests, radiotherapy, hormone therapy and second-generation hormonal treatments. CONCLUSIONS: The combination of radiotherapy and androgen-deprivation therapy is the treatment of choice. The addition of second-generation hormone therapy, plus the intensification of radiotherapy schedules, will likely change the treatment paradigm for these patients.

Bone health and therapeutic agents in advanced prostate cancer.

Prostate cancer is the most frequent genitourinary tumor worldwide. Maintaining an optimum bone health throughout the natural course of prostate cancer is an important aspect in the management of this disease, particularly in this at risk population of older and frail patients who experience bone loss related to androgen-deprivation therapy (ADT) and/or patients who develop bone metastases. The number of treatment options for advanced prostate cancer that combine ADT with docetaxel, new hormonal agents and/or radiotherapy has increased substantially in recent years. Bisphosphonates and other bone targeted agents such as denosumab have shown an improvement in bone mineral density and are suited for patients with treatment-related osteoporosis and/or bone metastases with an increased risk of skeletal-related events (SREs). In this context, the aim of this review is to analyse key aspects of bone health and therapies that can prevent the occurrence of SREs throughout the clinical course of prostate cancer, and how to combine them with new available treatments in this setting.

Extreme Hypofractionation with SBRT in Localized Prostate Cancer.

Prostate cancer is the most commonly diagnosed cancer among men around the world. Radiotherapy is a standard of care treatment option for men with localized prostate cancer. Over the years, radiation delivery modalities have contributed to increased precision of treatment, employing radiobiological insights to shorten the overall treatment time, improving the control of the disease without increasing toxicities. Stereotactic body radiation therapy (SBRT) represents an extreme form of hypofractionated radiotherapy in which treatment is usually delivered in 1-5 fractions. This review assesses the main efficacy and toxicity data of SBRT in non-metastatic prostate cancer and discusses the potential to implement this scheme in routine clinical practice.