Oncology

Prostate Cancer

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Stereotactic Ablative Radiotherapy for Oligometastatic Disease

clinical topic updates by Peter R. Carroll, MD, MPH

Overview

Stereotactic ablative radiotherapy (SABR) is a technique that accurately targets sites of disease involvement and delivers a highly ablative dose over 1 to 5 treatments. Although SABR appears to prolong androgen deprivation therapy (ADT)–free survival, whether that will translate to improved overall survival must be determined in prospective studies.

Expert Commentary

Peter R. Carroll, MD, MPH

Ken and Donna Derr – Chevron Distinguished Professor
Taube Family Distinguished Professor in Urology
Department of Urology
UCSF – Helen Diller Comprehensive Cancer Center
University of California, San Francisco
San Francisco, CA

“In certain subsets of patients with a very low metastatic burden, SABR might improve survival. We are hopeful, but that remains to be conclusively demonstrated.” 

Peter R. Carroll, MD, MPH

Increasingly, with the use of refined imaging techniques, we are identifying patients who have a very low metastatic burden, including metastases that are not detected by conventional imaging. SABR is being performed in various settings, both in practice and in clinical trials. There is some evidence to suggest that treating such individuals with SABR may lengthen the time to additional treatment or prolong ADT-free survival. In certain subsets of patients with a very low metastatic burden, SABR might improve survival as well. We are hopeful, but that remains to be conclusively demonstrated.

Two issues that arise in the treatment of men with oligometastatic disease are how to treat the primary tumor and how to treat the metastases. These are separate issues, but, in each case, there is evidence that both local and systemic treatments may improve outcomes. Recent findings from the STOMP, SABR-COMET, and ORIOLE trials demonstrated that treatment with SABR delayed the initiation of ADT in patients with a low metastatic burden of up to- 5 sites, depending on the trial. Now, these were relatively small trials, and whether longer ADT-free survival leads to improved overall survival has not yet been determined conclusively. In addition, not all of the men in these trials underwent advanced imaging (prostate-specific membrane antigen positron emission tomography). Maximal benefit appears to be in those where all metastatic sites identified on such imaging could be targeted.

Something else to appreciate is the importance of not only bone metastases but also lymph node metastases. At the University of California, San Francisco, we use prostate-specific membrane antigen positron emission tomography/computed tomography in high-risk patients to identify nodal metastases (regional and retroperitoneal) prior to surgery or radiation therapy. In my opinion, there may be a role for SABR in treating these nodal metastases, in addition to the bone metastases. Nodal metastases are not uncommon in patients who recur much later, after surgery; so, it is important to appreciate that different stages of disease may fall into the oligometastatic disease category.

When treating a patient with a known metastasis, such as in the lymph nodes, targeted lesions get a higher dose with SABR compared with the dose that is administered with standard nodal radiation whether at time of diagnosis or in those who fail after surgery and undergo salvage radiation In patients with lymph node metastases, both the positive lymph node and the surrounding lymph nodes are treated due to the concern of micrometastatic disease. In addition, many of the lymph nodes detected may be outside the standard field for radiation. Some practitioners have suggested that radiation therapy with radical intent to metastatic sites could be offered as an alternative to androgen receptor–directed therapy to delay systemic treatment in certain well-defined clinical scenarios. Although this might be a reasonable approach, further research is needed to determine which patients might benefit as compared with the alternative options. There are ongoing clinical trials evaluating how best to treat the primary tumor and how best to manage oligometastatic disease, and evidence suggests that both are likely important in patients with prostate cancer.

References

Al-Shafa F, Arifin AJ, Rodrigues GB, Palma DA, Louie AV. A review of ongoing trials of stereotactic ablative radiotherapy for oligometastatic cancers: where will the evidence lead? Front Oncol. 2019;9:543.

Boreta L, Gadzinski AJ, Wu SY, et al. Location of Recurrence by Gallium-68 PSMA-11 PET Scan in Prostate Cancer Patients Eligible for Salvage Radiotherapy. Urology. 2019;129:165-171.

D’Angelillo RM, Francolini G, Ingrosso G, et al. Consensus statements on ablative radiotherapy for oligometastatic prostate cancer: a position paper of Italian Association of Radiotherapy and Clinical Oncology (AIRO). Crit Rev Oncol Hematol. 2019;138:24-28. 

Moyer CL, Phillips R, Deek MP, et al. Stereotactic ablative radiation therapy for oligometastatic prostate cancer delays time‑to‑next systemic treatment. World J Urol. 2019;37(12):2623-2629.

Ost P, Reynders D, Decaestecker K, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36(5):446-453. 

Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patient s with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051-2058.

Phillips R, Lim SJ, Shi WY, et al. Primary outcomes of a phase II randomized trial of observation versus stereotactic ablative radiation for oligometastatic prostate cancer (ORIOLE). Int J Radiat Oncol Biol Phys. 2019;105(3):681.

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. doi: 10.1001/jamaoncol.2020.0147. [Epub ahead of print]

Peter R. Carroll, MD, MPH

Ken and Donna Derr – Chevron Distinguished Professor
Taube Family Distinguished Professor in Urology
Department of Urology
UCSF - Helen Diller Comprehensive Cancer Center
University of California, San Francisco
San Francisco, CA

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