De-Escalation of Therapy for Prostate Cancer

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men with around 1.4 million new cases every year. In patients with localized disease, management options include active surveillance (AS), radical prostatectomy (RP; with or without pelvic lymph node dissection), or radiotherapy to the prostate (with or without pelvic irradiation) with or without hormonotherapy. In advanced disease, treatment options include systemic treatment(s) and/or treatment to primary tumour and/or metastasis-directed therapies (MDTs). Specifically, in advanced stage, the current trend is earlier intensification of treatment such as dual or triple combination systemic treatments or adding treatment to primary and MDT to systemic treatment. However, earlier treatment intensification comes with the cost of increased morbidity and mortality resulting from drug-/treatment-related side effects. The main goal is and should be to provide the best possible care and oncologic outcomes with minimum possible side effects. This chapter will explore emerging possibilities to de-escalate treatment in PCa driven by enhanced insights into disease biology and the natural course of PCa such as AS in intermediate-risk disease or salvage versus adjuvant radiotherapy in post-RP patients. Considerations arising from advancements in PCa imaging and technological advancements in surgical and radiation therapy techniques including omitting pelvic lymph node dissection in the era of prostate-specific membrane antigen positron emitting tomography, the potential of MDT to delay/omit systemic treatment in metachronous oligorecurrence, and the efficacy of hypofractionation schemes compared with conventional fractionated radiotherapy will be discussed.