Efficacy of repeated PSMA PET-directed radiotherapy for oligorecurrent prostate cancer after initial curative therapy

Strahlenther Onkol. 2020 Nov;196(11):1006-1017. doi: 10.1007/s00066-020-01629-5. Epub 2020 May 12.

Abstract

Purpose: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT).

Patients and methods: Thirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2.

Results: The median follow-up duration was 39.5 months (18-60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2-3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07-3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12-12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07-154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2-3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9-19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3-17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9-8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1-41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8-13.47) of needing ADT at the last follow-up visit.

Conclusion: If patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.

Keywords: Biochemical progression; Metastatic Prostate cancer; Oligometastases; PSMA; Radio-oncology.

MeSH terms

  • Adenocarcinoma / diagnostic imaging
  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma / secondary*
  • Adenocarcinoma / surgery
  • Aged
  • Antigens, Neoplasm / analysis*
  • Antigens, Surface / analysis*
  • Biomarkers, Tumor / analysis*
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / radiotherapy
  • Bone Neoplasms / secondary
  • Disease Progression
  • Follow-Up Studies
  • Glutamate Carboxypeptidase II / analysis*
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Irradiation
  • Lymphatic Metastasis / radiotherapy
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / radiotherapy
  • Positron-Emission Tomography*
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / diagnostic imaging
  • Prostatic Neoplasms / radiotherapy
  • Prostatic Neoplasms / surgery*
  • Radiation Injuries / etiology
  • Radiotherapy, Image-Guided / adverse effects
  • Radiotherapy, Image-Guided / methods*

Substances

  • Antigens, Neoplasm
  • Antigens, Surface
  • Biomarkers, Tumor
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II