EMUC 2020: Regional Treatment of Metastasis: What For?

(UroToday.com) The European Multidisciplinary Congress on Urological Cancers (EMUC) 2020 virtual meeting featured a session on Oligometastatic Disease in Genitourinary Cancers including a presentation by Dr. Steven Joniau discussing the regional treatment of metastases. The rationale for treatment of the primary tumor and metastases in oligometastatic prostate cancer is to “break the chain” whereby aggressive local treatment halts the premetastatic niche and avoids further metastases. Furthermore, efficient treatment of metastases may also stop further metastatic spread and cross-talk with other micrometastases. With regard to oligometastatic disease, the “seek and destroy” method suggests that early and accurate detection of oligometastases provides an opportunity for metastasis-directed treatment with surgery or stereotactic body radiation therapy (SBRT).


There have been several important trials published over the last several years suggesting a role for metastasis directed treatment (MDT). In the STOMP trial,1 Salvage Treatment or Active Clinical Surveillance for Oligometastatic Prostate Cancer: a Randomized Phase II Trial (STOMP), Ost and colleagues randomly assigned 62 patients to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy), with a primary endpoint of androgen deprivation therapy (ADT)-free survival. 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 MDT group (HR 0.60, 80% CI 0.40 to 0.90; log-rank p = 0.11):

EMUC_ADT-free_survival.png



The single-arm prospective POPSTAR trial, Pilot Study of patients with Oligometastases from Prostate cancer treated with STereotactic Ablative Radiotherapy (POPSTAR), between 2013 and 2014, 33 consecutive patients received stereotactic ablative radiotherapy (SABR) (a single fraction of 20-Gy SABR to each lesion) to a total of 50 oligometastases and were followed for 2 years.2 Twenty patients had bone only, 12 had node only, and one had mixed disease. The 1 and 2-year local-PFS was 97% (95% CI 91-100) and 93% (95% CI 84-100), and distant PFS was 58% (95% CI: 43-77) and 39% (95% CI: 25-60), respectively. Among those not on ADT (n=22), the 2-year freedom from ADT rate was 48%.

The ORIOLE trial, Stereotactic Body Radiation for Prostate Oligometastases (ORIOLE)3 randomized 54 men with oligometastatic prostate cancer 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 prostate-specific antigen (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):

EMUC_SABR-COMET.png




For those patients in the stereotactic body radiotherapy arm that had a PSMA PET-CT scan, the proportion of men with disease progression at 6 months was 5% in those who did not have any untreated lesions, compared to 38% in those who did have some untreated PSMA avid lesions (p=0.03).

In 2019 the SABR-COMET study, Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic Tumors (SABR-COMET) (SABR-COMET) was published in The Lancet.4 This randomized, open-label phase 2 study randomized 99 patients (1:2) to receive either palliative standard of care treatments alone (control group) or standard of care plus stereotactic body radiotherapy to all metastatic lesions (SABR group). Over a median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group, median overall survival was 28 months (95% CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (HR 0.57, 95% CI 0.30-1.10; p=0.090). Recently published long-term outcomes of this trial showed durable findings.5 Over a median follow-up of 51 months, the 5-year OS rate was 17.7% in the control group (95% CI 6% to 34%) versus 42.3% in the SABR group (95% CI 28% to 56%; stratified log-rank p = 0.006), and the 5-year PFS rate was not reached in the control group (3.2%; 95% CI 0% to 14% at 4 years with last patient censored) and 17.3% in the SABR group (95% CI 8% to 30%; p = 0.001):

EMUC_SABR_group.png



Dr. Joniau provided the following take-home messages from his presentation on the rationale for MDT:
  • Treatment of limited metastatic recurrence in GU cancers by surgery or SBRT is feasible and appears to provide benefit in well-selected patients
  • Most patients are not cured following MDT, as most will develop further metastatic recurrence, therefore a delay of further metastatic recurrence should be the primary aim of MDT
  • Combination of systemic and metastasis-directed therapies may theoretically provide the best outcomes
  • Further research in this field is urgently needed

Presented by: Steven Joniau, MD, Ph.D., University Hospitals Leuven, Leuven, Belgium.

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 12th European Multidisciplinary Congress on Urological Cancers (EMUC) (#EMUC20 ), November 13th - 14th, 2020

References:
  1. 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.
  2. Siva S, Bressel M, Murphy DG, et al. Stereotactic Ablative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial. Eur Urol 2018 Oct;74(4):455-462.
  3. 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.
  4. Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): A randomized, phase 2, open-label trial. 2019 May 18;393(10185):2051-2058.
  5. Palma DA, Olson R, Harrow S, et al. Stereotactic Ablative Radiotherapy for Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial. J Clin Oncol. 2020 Sep 1;38(25):2830-2838.
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