Classification of oligometastatic prostate cancer with additional consideration for hormone sensitivity

Abstract

Hellman and Weichselbaum defined oligometastases as a distinct cancer state that has features falling between localized and systemically metastasized diseases, and is amenable to targeted localized therapy [1]. In phase 2 of the STOMP trial, metastasis-directed therapy was shown to extend the androgen deprivation therapy (ADT)-free survival time in patients with oligorecurrent prostate cancer [2]. In phase 3 of the randomized STAMPEDE trial, the benefit of administering local radiotherapy on the primary prostate cancer, in addition to ADT for metastatic lesions, was investigated, and local radiotherapy improved overall survival in patients with a low metastatic burden [3]. The results of these studies have attracted significant attention to targeted therapies for oligometastatic prostate cancer. Our understanding of the oligometastatic disease biology is far from complete, and the classification of cancer as oligometastatic largely depends on imaging findings. A project by the EORTC and the ESTRO analyzed the relevant clinical parameters in phase studies of oligometastatic disease. Based on the results, a comprehensive system for the characterization and classification of oligometastatic diseases was proposed [4]. This classification system can be applied regardless of the primary tumor type and is expected to find clinical use in the future. Oligometastatic diseases include a wide variety of pathologies and can be broadly divided into genuineor induced-oligometastases depending on the absence or presence of a history of poly-metastases. Induced-metastases, which occur when some metastatic lesions remain active after treatment, seem to have a greater metastatic potential than genuine-oligometastases. Therefore, the concept of oligometastatic cancer, as defined by the Advanced Prostate Cancer Consensus Conference as an oligoprogressive disease, applies not only to hormone-sensitive prostate cancer (HSPC) but also to castration-resistant prostate cancer (CRPC) [5]. However, because previous phase studies of oligometastatic prostate cancer have been limited to HSPC, there is no clear distinction between the two in the new classification system (Fig. 1). Castration-resistant prostate cancer is defined by the presence of either radiological or biochemical progression, or both; thus, such cases can still fall under repeat-/ induced-oligopersistence, a condition in which disease progression is absent on imaging. In the proposed classification, oligopersistence includes both HSPC and CRPC, which are two biologically distinct disease states that must be considered separately [6]. In fact, ongoing phase studies for oligometastatic cancers are differentiated as HSPCor CRPC-only entries. Additionally, the outcomes of targeted therapy for oligometastatic disease in patients with HSPC are different from those with CRPC [2, 3, 7–10]. Therefore, we propose that, when classifying prostate cancer as oligometastatic, information on hormone sensitivity should also be considered. Furthermore, oligometastatic diseases should be classified according to whether they are hormonesensitive or castration-resistant, rather than whether disease progression is present on current imaging. The TroMbone (ISRCTN15704862) and g-RAMPP (NCT02454543) trials in synchronous oligometastatic prostate cancer, as well as the TRAP (NCT03644303) and FORCE (NCT03556904) trials for oligoprogression, which study CRPCs, are currently underway; these will hopefully demonstrate the efficacy of targeted therapies for these conditions. * Soichiro Yoshida [email protected]