ASTRO 2021: Radiation Therapy for Very High Risk to Oligometastatic Prostate Cancer

(UroToday.com) The American Society for Radiation Oncology’s 2021 annual meeting included an educational session discussing multidisciplinary management of very high-risk prostate cancer and a presentation by Dr. Ronald Chen highlighting radiation therapy for very high-risk to oligometastatic prostate cancer. Dr. Chen notes that among high-risk prostate cancer patients, two trials (NCIC PR.3 and SPCG-7) showed an improvement in overall survival comparing lifelong ADT versus ADT + radiotherapy:



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Furthermore, also among high-risk prostate cancer patients, three trials (RTOG 8531, EORTC 22863, and RTOG 8610) have shown that the addition of ADT to radiotherapy improves survival outcomes compared to radiotherapy alone:

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Duration of ADT added to radiotherapy has also been assessed in several trials (RTOG 9202, EORTC 22961, and PCS-IV) showing that 28 months versus 4 months of ADT improves overall survival, 36 months versus 6 months of ADT improves overall survival, and no difference was noted between 36 months versus 18 months of ADT (DSS: HR 0.95, 95% CI 0.58-1.55; OS: HR 1.02, 95% CI 0.81-1.29):

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Dr. Chen emphasized that there are several important points of note regarding the aforementioned trials in high-risk prostate cancer:

  1. These trials used LHRH agonists, with (i) the duration of testosterone suppression being longer than the prescribed duration of LHRH agonist and (ii) replacement with LHRH antagonist clearly does not provide the same efficacy
  2. Node-positive prostate cancer was not included in the PCS-IV trial, which showed no difference in DSS Or OS among patients receiving radiotherapy + 18 months versus 36 months of ADT

Among patients with N+ prostate cancer, the RTOG 8531 trial assessed radiotherapy + immediate hormonal therapy versus radiotherapy + hormonal therapy at relapse among 173 patients N+ disease.1 With a median follow-up of 6.5 years, patients receiving radiotherapy + hormonal therapy had improved biochemical control versus those receiving hormones at the time of relapse:

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The ongoing NRG Oncology GU0009 trial is assessing a de-intensification arm (among patients with Decipher <= 0.8) randomizing patients to either radiotherapy + 24 months versus 12 months of ADT. The intensification arm (Decipher >0.8 or N1 disease) is randomizing patients to radiotherapy + 24 months versus radiotherapy + 24 months of ADT + 24 months of apalutamide + 24 months of abiraterone:

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Specific to N0 patients, the ongoing SPCG-15 trial (in Denmark, Norway, Finland, and Sweden) is randomizing 1,200 patients with cT3-T4/N0 to either radiotherapy (EBRT 78 Gy or EBRT/HDR) + ADT (6 months total androgen blockade + 18-27 months of abiraterone acetate or LHRH agonist) versus radical prostatectomy with extended nodal dissection (adjuvant/salvage radiotherapy per local guidelines). The primary endpoint for this trial is cause-specific survival.

Dr. Chen also discussed several important clinical trials in the oligometastatic prostate cancer disease space. In STAMPEDE arm H,2 2,061 men were randomized to either standard systemic treatments (ADT +/- chemotherapy) versus standard systemic treatments (ADT +/- chemotherapy) plus radiotherapy to the primary tumor. There were 819 (40%) men that had a low metastatic burden, 1,120 (54%) had a high metastatic burden, and the metastatic burden was unknown for 122 (6%). Radiotherapy improved FFS (HR 0.76, 95% CI 0.68-0.84) but not OS (HR 0.92, 95% CI 0.80-1.06). However, in a prespecified subgroup analysis, patients receiving radiotherapy to the prostate among patients with low metastatic burden, there was a significant improvement in OS (HR 0.68, 95% CI 0.52-0.90). Additional trials in this disease space include the ongoing SWOG 1802 trial (n = 1,273) randomizing men to standard systemic therapy versus systemic therapy + radical prostatectomy or radiotherapy. The PEACE-1 trial (n = 1,173) finished accruing patients and is a 2x2 trial design assessing ADT (plus docetaxel allowed) +/- abiraterone and +/- enzalutamide.

With regards to metastasis directed therapy, two trials have recently been published assessing this treatment approach. In the STOMP trial, Ost and colleagues randomly assigned 62 patients to either surveillance or metastasis-directed therapy of all detected lesions (surgery or stereotactic body radiotherapy), with a primary end point of ADT-free survival.3 At a median follow-up time of 3 years (IQR 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI 12 to 17 months) for the surveillance group and 21 months (80% CI 14 to 29 months) for the metastasis-directed therapy group (HR 0.60, 80% CI 0.40 to 0.90; log-rank p = 0.11):

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The second phase II trial published recently was the ORIOLE trial,4 randomizing 54 men in a 2:1 ratio to receive stereotactic body radiotherapy or observation. The primary endpoint for this trial was progression at 6 months, defined as a PSA increase, radiographic or symptomatic progression, ADT initiation, or death. Progression at 6 months occurred in 7 of 36 patients (19%) receiving stereotactic body radiotherapy and 11 of 18 patients (61%) undergoing observation (p = 0.005). Furthermore, treatment with stereotactic body radiotherapy improved median progression-free survival (not reached vs 5.8 months; HR 0.30, 95% CI 0.11-0.81; p = 0.002):

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Dr. Chen concluded his presentation of radiation therapy for very high-risk to oligometastatic prostate cancer with the following take-home points:

  • For high risk prostate cancer, radiotherapy improves overall survival and trials continue to refine the duration of ADT
  • For oligometastatic prostate cancer, low-burden disease patients have a survival benefit with radiotherapy, and metastasis-direct SBRT delays time to ADT

Presented by: Ronald Chen, MD, MPH, Department of Radiation Oncology, Associate Director of Health Equity, University of Kansas, Kansas City, KS

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021.

References:

  1. Lawton CA, Winter K, Grignon D, et al. Androgen suppression plus radiation versus radiation alone for patients with stage D1/pathologic node-positive adenocarcinoma of the prostate: Updated results based on national prospective randomized trial Radiation Therapy Oncology Group 85-31. J Clin Oncol. 2005 Feb 1;23(4):800-807.
  2. Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392(10162):2353-2366.
  3. Ost P, Reynders D, Decaestecker K, et al. Surveillance of Metastasis-Directed Therapy for Oligometastatic Prostate Cancer Recurrence: A Prospective, Randomized, Multicenter Phase II Trial. J Clin Oncol 2018 Feb 10;36(5):446-453.
  4. Phillips R, Shi WY, Deek M, et al. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol 2020 Mar 26;6(5):650-659.
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