Management of metastatic hormone-sensitive prostate cancer - Current treatment options, criteria for progression and switch of therapy

Abstract

Based on convincing data with an increase in overall survival (OS), the current national and international European Guidelines (S3, ESMO, EAU) recommend a combination therapy with ADT plus Docetaxel or plus the next-generation antiandrogens abiraterone (plus prednisone/prednisolone), apalutamide or enzalutamide as standard treatment for mHSPC patients with a good performance status (ECOG 0-1). Abiraterone received approval only for use in patients with newly diagnosed (de novo) high-risk mHSPC. There is no restrictive approval status for docetaxel in mHSPC. However, the current S3 guideline differentiates in the level of recommendation with regard to tumour volume: a "strong" recommendation is given in high-volume mHSPC, while only a "may" recommendation is given for low-volume mHSPC due to inconsistent data. Apalutamide and enzalutamide are treatment options in a broad range of mHSPC patients. It can be difficult in clinical practice to determine disease progression under ongoing treatment. Generally, a rising PSA level is the first sign of progression, followed by radiographic and clinical progress. In the hormone-sensitive situation, the decision of when to change treatment can be based on the progression to castration-resistant prostate cancer as defined by the EAU guidelines; in the castration-resistant situation, it can be based on progression as per PCWG3 criteria of the Prostate Cancer Clinical Trials Working Group. At least two of the three criteria (PSA progression, radiographic progression, and clinical deterioration) should be met to determine progression and to change treatment. However, since advanced prostate cancer is a very heterogeneous disease, the decision to change treatment in clinical practice must ultimately be made on a case-by-case basis.