Systemic and tumor-directed therapy for oligometastatic prostate cancer: study protocol for a phase II trial for veterans with de novo oligometastatic disease

BMC Cancer. 2019 Apr 1;19(1):291. doi: 10.1186/s12885-019-5496-5.

Abstract

Background: The treatment paradigm for metastatic hormone-sensitive prostate cancer (mHSPC) patients is evolving. PET/CT now offers improved sensitivity and accuracy in staging. Recent randomized trial data supports escalated hormone therapy, local primary tumor therapy, and metastasis-directed therapy. The impact of combining such therapies into a multimodal approach is unknown. This Phase II single-arm clinical trial sponsored and funded by Veterans Affairs combines local, metastasis-directed, and systemic therapies to durably render patients free of detectable disease off active therapy.

Methods: Patients with newly-diagnosed M1a/b prostate cancer (PSMA PET/CT staging is permitted) and 1-5 radiographically visible metastases (excluding pelvic lymph nodes) are undergoing local treatment with radical prostatectomy, limited duration systemic therapy for a total of six months (leuprolide, abiraterone acetate with prednisone, and apalutamide), metastasis-directed stereotactic body radiotherapy (SBRT), and post-operative fractionated radiotherapy if pT ≥ 3a, N1, or positive margins are present. The primary endpoint is the percent of patients achieving a serum PSA of < 0.05 ng/mL six months after recovery of serum testosterone ≥150 ng/dL. Secondary endpoints include time to biochemical progression, time to radiographic progression, time to initiation of alternative antineoplastic therapy, prostate cancer specific survival, health related quality-of-life, safety and tolerability.

Discussion: To our knowledge, this is the first trial that tests a comprehensive systemic and tumor directed therapeutic strategy for patients with newly diagnosed oligometastatic prostate cancer. This trial, and others like it, represent the critical first step towards curative intent therapy for a patient population where palliation has been the norm.

Trial registration: Clinicaltrials.gov identifier: NCT03298087 (registration date: September 29, 2017).

Keywords: Abiraterone; Androgen deprivation therapy; Apalutamide; Leuprolide; Metastasis-directed therapy; Oligometastases; Prostate cancer; Radical prostatectomy; Stereotactic body radiotherapy.

Publication types

  • Clinical Trial Protocol
  • Clinical Trial, Phase II

MeSH terms

  • Abiraterone Acetate / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / blood
  • Combined Modality Therapy
  • Humans
  • Leuprolide / therapeutic use
  • Male
  • Middle Aged
  • Neoplasm Micrometastasis / diagnostic imaging
  • Neoplasm Micrometastasis / drug therapy
  • Neoplasm Micrometastasis / radiotherapy
  • Neoplasm Micrometastasis / therapy*
  • Prednisone / therapeutic use
  • Prostate-Specific Antigen / blood*
  • Prostatectomy*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / diagnostic imaging
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / therapy
  • Radiosurgery*
  • Thiohydantoins / therapeutic use
  • Treatment Outcome
  • Veterans
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Thiohydantoins
  • apalutamide
  • Prostate-Specific Antigen
  • Leuprolide
  • Abiraterone Acetate
  • Prednisone

Associated data

  • ClinicalTrials.gov/NCT03298087