Metastatic Hormone-Sensitive Prostate Cancer: New Therapeutic Strategies to Improve Patient Outcome

About this Research Topic

Background

In the last 20 years, prostate cancer has undergone a major revolution. The development of Prostate Specific Antigen (PSA) and the surgical refinements alongside technical advances in radiotherapy have promoted an early diagnosis and treatment and maintenance of the quality of life for the majority of patients with localized prostate cancer while promoting long-term survival. Still, whether radical treatment is actually required for all patients with an early diagnosis remains a question. Conversely, androgen deprivation therapy (ADT) alone has been the gold standard of care (SOC) in the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) for the last 60 years and very little improvement has been made since. A combination therapy of ADT plus docetaxel chemotherapy in metastatic castration-resistant prostate cancer (mCRPC) showed a survival advantage, albeit a comparatively short improvement compared to SOC. With the development of newer androgen receptor axis target agents (ARTA) such as Abiraterone, Enzalutamide, Apalutamide, and Darolutamide, a significant survival benefit in that clinical scenario (CRPC) was observed with a combination of ADT plus ARTAs.

Recently, combination therapies of ADT plus ARTAs have become the new SOC in mHSPC. Moreover, new data has emerged on the now so-called triplet therapy of ADT plus Docetaxel plus Darolutamide and were able to demonstrate a significant survival advantage compared to the SOC of ADT and docetaxel, if not for all, at least for a selective group of mHSPC patients. The triplet therapy of Abiraterone plus Docetaxel plus ADT also showed a significant survival advantage in the setting of high-volume metastasis compared to the doublet therapy of Docetaxel plus ADT. But, in all pivotal phase 3 studies of doublets and triplets therapies, patients were staged with conventional imaging methods. We are now largely using PETscan PSMA to stage patients and analyzing data regarding the volume of metastasis using this new technology has added another dimension to the controversy. In the last few years, two poly (ADP-ribose) polymerase (iPARP) inhibitors (Olaparib and Rucaparib) have been approved for metastatic castration-resistant prostate cancer (mCPRC), opening a new horizon in the treatment of prostate cancer. And recently 177lutetium-PSMA-617 was approved by the FDA for certain patients with advanced prostate cancer adding theragnostic to the armamentarium of advanced prostate cancer treatments. Still, many questions remain largely unanswered.

In this Research Topic, we aim to review, add knowledge, and further discuss some of these questions. Therewith, we are interested in new research regarding metastatic hormone-sensitive prostate cancer that covers:

1. What is the best approach for patients with clinically positive nodes (cTxN1) on magnetic resonance imaging or PET-PSMA positive imaging?
2. Is stereotactic radiotherapy (SRT) to oligometastatic disease by PET-PSMA enough or do we need to associate short-term ADT or even treatment intensification for better response?
3. Does N+ equals to low volume M+ in oligometastasis?
4. Should docetaxel no longer be used primarily in mHSPC?
5. Should primary – de novo mHSPC be treated similarly to patients that have progressed after failure of primary local radical treatment with the same doublet therapy?
6. What is the role of surgery for de novo mHSPC that have responded to ADT+ARAT? Is radiotherapy for prostate cancer preferable to surgery?
7. What is the best form of therapy for the ever-growing number of older and frail patients with mHSPC?
8. Who is the ideal candidate for triple therapy?
9. Are we using real-life valid clinical endpoints for the evaluation of therapy responses?

Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.

Keywords: Prostate Cancer, Metastasis, Hormone Therapy, mHSPC, PSMA PET, combined therapy, surgery, clinical endpoints, management, patient care

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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