Upfront metastasis-directed therapy in oligorecurrent prostate cancer does not decrease the time from initiation of androgen deprivation therapy to castration resistance

Luca Triggiani,Ciro Franzese,Marco Lorenzo Bonù,Fabio Trippa,Paolo Ghirardelli,Roberto Bortolus,Rosario Mazzola,Ernesto Maranzano,Andrea Lancia,G Alicino ,Gianluca Ingrosso,Filippo Alongi,V Vavassori ,A Magli ,Fabio Matrone,Marta Scorsetti,Giulio Francolini,Beatrice Detti,Alessio Bruni,Davide Tomasini,Stefano Maria Magrini

doi:10.1007/s12032-021-01518-6

Abstract

The aim of the present study was to explore the potential impact of upfront metastases-directed therapy (MDT) in terms of prolongation of castration-sensitive phase in a series of oligorecurrent castration-sensitive prostate cancer (PC) patients. The present article is a multicenter retrospective study. The population of interest was castrate-sensitive oligorecurrent PC, defined as the presence of 1–3 uptakes in non-visceral sites such as bones or nodes detected by means of 18F-Choline PET/CT or 68-Gallium PSMA PET/CT. Primary endpoint was the time to castration resistance. Secondary endpoints were ADT-free survival, local progression-free survival, and overall survival. Eighty-two patients and 118 lesions were analyzed. The median time to castration resistance for the entire population of the study was 49 months (95% CI 43.6–54.4 months). The 1- and 2-year TTCR-free survival rates were 94% and 82%, respectively. At the time of analysis, 52 patients were still in the castration-sensitive phase of the disease. In this cohort of patients, the median ADT-free survival was 20 months (range 3–69 months). On the other hand, during follow-up 30 patients switched to the castration-resistant phase of disease. In this last group of patients, the median ADT-free survival was 20 months (range 4–50 months). After the ADT administration, the median castration-sensitive phase was 29 months (range 5–71 months). Castration resistance generally occurs at a median follow-up of 24–36 months following ADT. In the current study, upfront MDT does not decrease the time from initiation of ADT to castration resistance.

Highlights

The management of metastatic castrationsensitive prostate cancer (PC) relied on the administration of androgen deprivation therapy (ADT) with Luteinizing Hormone-Releasing Hormone (LH-RH) analogues or antagonist
time to castration resistance (TTCR) was defined as the time between the starting of ADT after SBRT and three consecutive rising in PSA resulting in two 50% increases over the nadir and PSA > 2 ng/ml
Forty-two percent of patients were treated for single metastases, while the remaining 58% received the SBRT treatment for two or more metastases

Summary

Introduction

The management of metastatic castrationsensitive prostate cancer (PC) relied on the administration of androgen deprivation therapy (ADT) with Luteinizing Hormone-Releasing Hormone (LH-RH) analogues or antagonist. After first-line ADT, disease progression represents a common event due to the development of the castration--resistant phase that generally occurs at a median follow-up of 24–36 months [2,3,4] For this reason, ADT for metastatic PC is largely considered a palliative treatment and, in addition, the administration of ADT itself can be burdened by the onset of non-negligible adverse events such as cardiovascular events, metabolic syndrome, sarcopenia, sexual dysfunction, and osteoporosis [5]. In the setting of oligorecurrent castration-sensitive PC a substantial amount of literature experiences, characterized by several levels of evidence, recently showed that metastasis-directed therapy (MDT) using high dose radiotherapy (SBRT) might represent a viable curative option able to improve disease control and significantly delay the administration of palliative ADT [6,7,8] It is currently object of debate if MDT is able to prolong the time to castration resistance (TTCR) onset or negatively modify the natural history of the castration-sensitive PC

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