Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment

Prostate. 2021 Jun;81(9):543-552. doi: 10.1002/pros.24132. Epub 2021 Apr 27.

Abstract

Background: Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed.

Materials and methods: The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS.

Results: The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis.

Conclusions: MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.

Keywords: abiraterone; enzalutamide; oligometastasis; prostate cancer; stereotactic radiotherapy.

MeSH terms

  • Androstenes / administration & dosage*
  • Antineoplastic Agents / administration & dosage
  • Benzamides / administration & dosage*
  • Combined Modality Therapy / methods
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis* / pathology
  • Neoplasm Metastasis* / radiotherapy
  • Neoplasm Staging
  • Nitriles / administration & dosage*
  • Phenylthiohydantoin / administration & dosage*
  • Prognosis
  • Progression-Free Survival
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms, Castration-Resistant* / blood
  • Prostatic Neoplasms, Castration-Resistant* / drug therapy
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Prostatic Neoplasms, Castration-Resistant* / radiotherapy
  • Radiosurgery / methods*
  • Treatment Outcome

Substances

  • Androstenes
  • Antineoplastic Agents
  • Benzamides
  • Nitriles
  • Phenylthiohydantoin
  • enzalutamide
  • Prostate-Specific Antigen
  • abiraterone