Metastasis-Directed Therapy Shows Promise in Oligorecurrent Prostate Cancer

Author(s):

For patients with oligorecurrent prostate cancer, androgen deprivation therapy–free survival was superior for those assigned to metastasis-directed therapy versus surveillance.

Piet Ost, MD, PhD

For patients with oligorecurrent prostate cancer, androgen deprivation therapy (ADT)—free survival was superior for those assigned to metastasis-directed therapy (MDT) versus surveillance, according to findings from a phase II trial published in the Journal of Clinical Oncology.

Patients in the study (N = 62) had asymptomatic oligorecurrent prostate cancer and had experienced biochemical recurrence after primary treatment with curative intent, had 3 or fewer extracranial metastatic lesions on PET-CT scan, and serum testosterone levels >50 ng/mL. At a median follow-up of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival in the intent-to-treat (ITT) population was 13 months (80% CI, 12-17) for the surveillance group and 21 months (80% CI, 14-29) for the MDT group (HR, 0.60; 80% CI, 0.40-0.90]; log-rank P = .11).

Patients were recruited into the multicenter, randomized phase II trial from August 2012 through August 2015. Thirty-one patients were randomized to surveillance and 31 were randomized to MDT. Stereotactic body radiotherapy (SBRT) was the most commonly used MDT (N = 25). Five patients underwent bilateral salvage pelvic lymph node dissection (sPLND) of the true pelvis, with removal of all nodal and fibrofatty tissue at the external and internal iliac regions and the obturator fossa region, and 1 underwent lung metastasectomy.

Researchers observed no symptomatic or local progression in the MDT group compared with 3 and 6 such occurrences, respectively, in the surveillance group.

Eleven patients in the MDT group were treated with a repeated course of MDT because of oligometastatic progression at the time of first radiographic progression, and 2 patients received 2 additional courses of MDT for oligometastatic progression. There was no significant interaction observed between the effect of MDT and PSA doubling time (P value of interaction = .35) or the location of metastases (P value of interaction = .31).

Overall, 74% of patients treated with MDT had a PSA decline compared with 42% in the surveillance arm. The median time until PSA progression for the ITT population was 6 months (80% CI, 4-7) for the surveillance group versus 10 months (80% CI, 8-13 months) in the MDT group (HR, 0.53; 80% CI, 0.37-0.77; P = .03). HR was 0.52 (80% CI, 0.36-0.76; P = .02) in the per protocol analysis. Seventy-five percent of patients treated with MDT experienced a PSA decline compared with 35% in the surveillance arm

“A remarkable observation was the fact that 35% of patients undergoing surveillance experienced spontaneous PSA declines without receiving any therapy,” lead author Piet Ost, MD, PhD, Department of Radiotherapy, Ghent University Hospital, and coinvestigators wrote. “However, these declines were not durable, as demonstrated by the fact that only approximately 20% of men were free from PSA progression at 1-year follow-up and approximately 10% at 2-year follow-up.”

Investigators found that quality of life (QOL) scores were similar between the arms at baseline and remained comparable at 3-month and 1-year follow-up. There were no clinically relevant changes in health-related QOL scores between the two study arms across all visits. Overall, health-related QOL scores remained stable for both groups at baseline, 3 months, and 1 year.

Six of the 36 patients (17%) treated with MDT experienced a grade 1 toxicity, though no patient experienced toxicity greater than grade 2. Following SBRT, investigators observed temporary looser stools (n = 1) and temporary muscle soreness (n = 1). One patient who underwent a video-assisted thoracoscopic lung metastasectomy developed thoracic wall pain requiring nonopioid analgesics for 6 months.

Following sPLND, investigators observed hypoesthesia of the genitofemoral nerve (n = 1), lymphorrhea (n = 1), and scrotal and penile edema (n = 1).

Ost P, Decaestecker K Fonteyne V, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial [published online December 14, 2017]. J Clin Oncol. doi: 10.1200/JCO.2017.75.4853.