THE ROLE OF STEREOTACTIC ABLATIVE RADIOTHERAPY IN THE TREATMENT OF OLIGOMETASTATIC DISEASE – A CLINICAL REVIEW
DOI:
https://doi.org/10.31435/ijitss.2(50).2026.5849Keywords:
Oligometastatic Disease, Stereotactic Ablative Radiotherapy, Ablation, Overall Survival, Targeted Therapy, BiomarkersAbstract
Oligometastatic disease (OMD) is defined as an intermediate stage between localised cancer and widespread metastasis. The objective of this paper is to critically evaluate the clinical efficacy and safety of stereotactic ablative body radiation (SABR) in the treatment of OMD.
This evaluation is based on a review of randomised trials from 2012 to 2025. A comprehensive analysis of pivotal clinical trials has revealed that the utilisation of ablation therapy is associated with a substantial enhancement in progression-free survival and overall survival, particularly in carefully selected patient populations. This assertion is corroborated by empirical evidence from studies conducted on prostate cancer (STOMP, ORIOLE) and specific subgroups of lung cancer (SINDAS). However, a discrepancy in outcomes was observed between patients receiving modern immunotherapy (NRG-LU002) and those treated for breast cancer (NRG-BR002), indicating a significant correlation between the efficacy of SABR and tumour biology, as well as the systemic treatment regimen employed.
A thorough analysis of the existing evidence was conducted, encompassing the limitations arising from population heterogeneity, inadequate sample sizes in clinical trials, and the paucity of large-scale phase III trials for numerous histopathological types. The review also underscores the pivotal function of meticulous patient selection based on biomarkers, including circulating tumour DNA.
The clinical findings suggest that SABR is a safe and highly effective method that allows for the deferral of toxic systemic treatment in selected patients. However, definitive standards for all subgroups will be established by ongoing phase III trials.
References
Chalkidou, A., Macmillan, T., Grzeda, M. T., Peacock, J., Summers, J., Eddy, S., Coker, B., Patrick, H., Powell, H., Berry, L., Webster, G., Ostler, P., Dickinson, P. D., Hatton, M. Q., Henry, A., Keevil, S., Hawkins, M. A., Slevin, N., & van As, N. (2021). Stereotactic ablative body radiotherapy in patients with oligometastatic cancers: A prospective, registry-based, single-arm, observational, evaluation study. The Lancet Oncology, 22(1), 98–106. https://doi.org/10.1016/S1470-2045(20)30537-4
Chaudhuri, A. A., Chabon, J. J., Lovejoy, A. F., Newman, A. M., Stehr, H., Azad, T. D., Khodadoust, M. S., Esfahani, M. S., Liu, C. L., Zhou, L., Scherer, F., Kurtz, D. M., Say, C., Carter, J. N., Merriott, D. J., Dudley, J. C., Binkley, M. S., Modlin, L., Padda, S. K., . . . Diehn, M. (2017). Early detection of molecular residual disease in localised lung cancer by circulating tumour DNA profiling. Cancer Discovery, 7(12), 1394–1403. https://doi.org/10.1158/2159-8290.CD-17-0716
Chmura, S., Winter, K. A., Woodward, W. A., Borges, V. F., Salama, J. K., Al-Hallaq, H. A., Matuszak, M., Milano, M. T., Jaskowiak, N. T., Bandos, H., Bazan, J. G., Nordal, R. A., Lee, D. Y., Smith, B. D., Mamounas, E. P., & White, J. R. (2022). NRG-BR002: A phase IIR/III trial of standard-of-care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection for newly diagnosed oligometastatic breast cancer. Journal of Clinical Oncology, 40(17_suppl), LBA1000. https://doi.org/10.1200/JCO.2022.40.16_suppl.1007
Deek, M. P., Van der Eecken, K., Sutera, P., Deek, R. A., Fonteyne, V., Mendes, A. A., Decaestecker, K., Kiess, A. P., Lumen, N., Phillips, R., De Bruycker, A., Mishra, M., Rana, Z., Molitoris, J., Lambert, B., Delrue, L., Wang, H., Lowe, K., Verbeke, S., . . . Tran, P. T. (2022). Long-term outcomes and genetic predictors of response to metastasis-directed therapy versus observation in oligometastatic prostate cancer: Analysis of STOMP and ORIOLE trials. Journal of Clinical Oncology, 40(29), 3377–3382. https://doi.org/10.1200/JCO.22.00644
Gomez, D. R., Blumenschein, G. R., Jr., Lee, J. J., Hernandez, M., Ye, R., Camidge, D. R., Doebele, R. C., Skoulidis, F., Gaspar, L. E., Gibbons, D. L., Karam, J. A., Kavanagh, B. D., Tang, C., Komaki, R., Louie, A. V., Palma, D. A., Tsao, A. S., Sepesi, B., William, W. N., . . . Heymach, J. V. (2016). Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: A multicentre, randomised, controlled, phase 2 study. The Lancet Oncology, 17(12), 1672–1682. https://doi.org/10.1016/S1470-2045(16)30532-0
Gomez, D. R., Tang, C., Zhang, J., Blumenschein, G. R., Jr., Hernandez, M., Lee, J. J., Ye, R., Palma, D. A., Louie, A. V., Camidge, D. R., Doebele, R. C., Skoulidis, F., Gaspar, L. E., Welsh, J. W., Gibbons, D. L., Karam, J. A., Kavanagh, B. D., Tsao, A. S., Sepesi, B., . . . Heymach, J. V. (2019). Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer: Long-term results of a multi-institutional, phase II, randomised study. Journal of Clinical Oncology, 37(18), 1558–1565. https://doi.org/10.1200/JCO.19.00201
Guckenberger, M., Lievens, Y., Bouma, A. B., Collette, L., Dekker, A., deSouza, N. M., Dingemans, A. C., Fournier, B., Hurkmans, C., Lecouvet, F. E., Meattini, I., Méndez Romero, A., Ricardi, U., Russell, N. S., Schanne, D. H., Scorsetti, M., Tombal, B., Verellen, D., Verfaillie, C., & Ost, P. (2020). Characterisation and classification of oligometastatic disease: A European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation. The Lancet Oncology, 21(1), e18–e28. https://doi.org/10.1016/S1470-2045(19)30718-1
Hellman, S., & Weichselbaum, R. R. (1995). Oligometastases. Journal of Clinical Oncology, 13(1), 8–10. https://doi.org/10.1200/JCO.1995.13.1.8
Hong, J. C., Ayala-Peacock, D. N., Lee, J., Blackstock, A. W., Okunieff, P., Sung, M. W., & Salama, J. K. (2018). Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis. PLOS ONE, 13(4), e0195149. https://doi.org/10.1371/journal.pone.0195149
Iyengar, P., All, S., Berry, M. F., Boike, T. P., Bradfield, L., Dingemans, A.-M. C., Feldman, J., Gomez, D. R., Hesketh, P. J., Jabbour, S. K., Jeter, M., Josipovic, M., Lievens, Y., McDonald, F., Perez, B. A., Ricardi, U., Ruffini, E., De Ruysscher, D., Saeed, H., . . . Guckenberger, M. (2023). Treatment of oligometastatic non-small cell lung cancer: An ASTRO/ESTRO clinical practice guideline. Practical Radiation Oncology, 13(5), 393–412. https://doi.org/10.1016/j.prro.2023.04.004
Iyengar, P., Hu, C., Gomez, D. R., Timmerman, R. D., Simone, C. B., Robinson, C. G., Gerber, D. E., Wagar, S. N., Donington, J., Swisher, S., Weldon, M., Wu, J., Faller, B. A., Rashdan, S., Stephans, K. L., Sampson, P., Higgins, K. A., Nowak, R. K., Lyness, J., & Bradley, J. D. (2024). NRG-LU002: Randomised phase II/III trial of maintenance systemic therapy versus local consolidative therapy (LCT) plus maintenance systemic therapy for limited metastatic non-small cell lung cancer (NSCLC). Journal of Clinical Oncology, 42(16_suppl), 8506. https://doi.org/10.1200/JCO.2024.42.16_suppl.8506
Iyengar, P., Wardak, Z., Gerber, D. E., Tumati, V., Ahn, C., Hughes, R. S., Dowell, J. E., Cheedella, N., Nedzi, L., Westover, K. D., Pulipparacharuvil, S., Choy, H., & Timmerman, R. D. (2018). Consolidative radiotherapy for limited metastatic non-small-cell lung cancer: A phase 2 randomised clinical trial. JAMA Oncology, 4(1), e173501. https://doi.org/10.1001/jamaoncol.2017.3501
Kumar, A., Straka, C. A., Courtney, P. T., Vitzthum, L. K., Riviere, P., & Murphy, J. D. (2021). Cost-effectiveness analysis of stereotactic ablative radiation therapy in patients with oligometastatic cancer. International Journal of Radiation Oncology, Biology, Physics, 109(5), 1185–1194. https://doi.org/10.1016/j.ijrobp.2020.09.045
Lehrer, E. J., Singh, R., Wang, M., Chinchilli, V. M., Trifiletti, D. M., Ost, P., Siva, S., Meng, M.-B., Tchelebi, L., & Zaorsky, N. G. (2021). Safety and survival rates associated with ablative stereotactic radiotherapy for patients with oligometastatic cancer: A systematic review and meta-analysis. JAMA Oncology, 7(1), 92–106. https://doi.org/10.1001/jamaoncol.2020.6146
Lievens, Y., Guckenberger, M., Gomez, D., Hoyer, M., Iyengar, P., Kindts, I., Méndez Romero, A., Nevens, D., Palma, D., Park, C., Ricardi, U., & Scorsetti, M. (2020). Defining oligometastatic disease from a radiation oncology perspective: An ESTRO-ASTRO consensus document. Radiotherapy and Oncology, 148, 157–166. https://doi.org/10.1016/j.radonc.2020.04.003
Mangoni, M., Borghesi, S., Aristei, C., & Becherini, C. (2022). Radiobiology of stereotactic radiotherapy. Reports of Practical Oncology and Radiotherapy, 27(1), 57–62. https://doi.org/10.5603/RPOR.a2022.0005
McDonald, F. (2015). Stereotactic ablative radiotherapy for oligometastatic non-small cell lung cancer (SARON) (ClinicalTrials.gov Identifier NCT02417662). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT02417662
Milano, M. T., Katz, A. W., Zhang, H., & Okunieff, P. (2012). Oligometastases treated with stereotactic body radiotherapy: Long-term follow-up of a prospective study. International Journal of Radiation Oncology, Biology, Physics, 83(3), 878–886. https://doi.org/10.1016/j.ijrobp.2011.08.036
Moding, E. J., Nabet, B. Y., Alizadeh, A. A., & Diehn, M. (2021). Detecting liquid remnants of solid tumours: Circulating tumour DNA minimal residual disease. Cancer Discovery, 11(12), 2968–2986. https://doi.org/10.1158/2159-8290.CD-21-0634
Nabrinsky, E., Macklis, J., & Bitran, J. (2022). A review of the abscopal effect in the era of immunotherapy. Cureus, 14(9), e29620. https://doi.org/10.7759/cureus.29620
Ost, P., Reynders, D., Decaestecker, K., Fonteyne, V., Lumen, N., De Bruycker, A., Lambert, B., Delrue, L., Bultijnck, R., Claeys, T., Goetghebeur, E., Villeirs, G., De Man, K., Ameye, F., Billiet, I., Joniau, S., Vanhaverbeke, F., & De Meerleer, G. (2018). Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: A prospective, randomised, multicentre phase II trial. Journal of Clinical Oncology, 36(5), 446–453. https://doi.org/10.1200/JCO.2017.75.4853
Palma, D. A. (2018). Stereotactic ablative radiotherapy for comprehensive treatment of 4–10 oligometastatic tumours (SABR-COMET-10) (ClinicalTrials.gov Identifier NCT03721341). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03721341
Palma, D. A. (2019). Stereotactic ablative radiotherapy for comprehensive treatment of oligometastatic (1–3 metastases) cancer (SABR-COMET-3) (ClinicalTrials.gov Identifier NCT03862911). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT03862911
Palma, D. A. (2023). A randomised phase III trial of stereotactic ablative radiotherapy for patients with up to 10 oligometastases and a synchronous primary tumour (SABR-SYNC) (ClinicalTrials.gov Identifier NCT05717166). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT05717166
Palma, D. A., Olson, R., Harrow, S., Gaede, S., Louie, A. V., Haasbeek, C., Mulroy, L., Lock, M., Rodrigues, G. B., Yaremko, B. P., Schellenberg, D., Ahmad, B., Griffioen, G., Senthi, S., Swaminath, A., Kopek, N., Liu, M., Moore, K., Currie, S., . . . Senan, S. (2019). Stereotactic ablative radiotherapy versus standard-of-care palliative treatment in patients with oligometastatic cancers (SABR-COMET): A randomised, phase 2, open-label trial. The Lancet, 393(10185), 2051–2058. https://doi.org/10.1016/S0140-6736(18)32487-5
Palma, D. A., Olson, R., Harrow, S., Gaede, S., Louie, A. V., Haasbeek, C., Mulroy, L., Lock, M., Rodrigues, G. B., Yaremko, B. P., Schellenberg, D., Ahmad, B., Senthi, S., Swaminath, A., Kopek, N., Liu, M., Moore, K., Currie, S., Schlijper, R., . . . Senan, S. (2020). Stereotactic ablative radiotherapy for the comprehensive treatment of oligometastatic cancers: Long-term results of the SABR-COMET phase II randomised trial. Journal of Clinical Oncology, 38(25), 2830–2838. https://doi.org/10.1200/JCO.20.00818
Phillips, R., Shi, W. Y., Deek, M., Radwan, N., Lim, S. J., Antonarakis, E. S., Rowe, S. P., Ross, A. E., Gorin, M. A., Deville, C., Greco, S. C., Wang, H., Denmeade, S. R., Paller, C. J., Dipasquale, S., DeWeese, T. L., Song, D. Y., Wang, H., Carducci, M. A., . . . Tran, P. T. (2020). Outcomes of observation versus stereotactic ablative radiation for oligometastatic prostate cancer: The ORIOLE phase 2 randomised clinical trial. JAMA Oncology, 6(5), 650–659. https://doi.org/10.1001/jamaoncol.2020.0147
Ramasamy, G., Muanza, T., Kasymjanova, G., & Agulnik, J. (2024). Models and biomarkers for local response prediction in early-stage and oligometastatic non-small cell lung cancer patients treated with stereotactic body radiation therapy using machine learning. Cureus, 16(12), e75819. https://doi.org/10.7759/cureus.75819
Reynders, K., Illidge, T., Siva, S., Chang, J. Y., & De Ruysscher, D. (2015). The abscopal effect of local radiotherapy: Using immunotherapy to make a rare event clinically relevant. Cancer Treatment Reviews, 41(6), 503–510. https://doi.org/10.1016/j.ctrv.2015.03.011
Rim, C. H., Cho, W. K., Park, S., Yoon, W. S., & Yang, D. S. (2023). Role of local ablative treatment in oligometastatic non-small cell lung cancer: A meta-analysis. International Journal of Surgery, 109(4), 1006–1014. https://doi.org/10.1097/JS9.0000000000000339
Salama, J. K., & Milano, M. T. (2014). Radical irradiation of extracranial oligometastases. Journal of Clinical Oncology, 32(26), 2902–2912. https://doi.org/10.1200/JCO.2014.55.9567
Scorsetti, M., Comito, T., Tozzi, A., Navarria, P., Fogliata, A., Clerici, E., Mancosu, P., Reggiori, G., Rimassa, L., Torzilli, G., Tomatis, S., Santoro, A., & Cozzi, L. (2015). Final results of a phase II trial for stereotactic body radiation therapy for patients with inoperable liver metastases from colorectal cancer. Journal of Cancer Research and Clinical Oncology, 141(3), 543–553. https://doi.org/10.1007/s00432-014-1833-x
Tang, C., Msaouel, P., Hara, K., Choi, H., Le, V., Shah, A. Y., Wang, J., Jonasch, E., Choi, S., Nguyen, Q.-N., Das, P., Prajapati, S., Yu, Z., Khan, K., Powell, S., Murthy, R., Sircar, K., & Tannir, N. M. (2021). Definitive radiotherapy in lieu of systemic therapy for oligometastatic renal cell carcinoma: A single-arm, single-centre, feasibility, phase 2 trial. The Lancet Oncology, 22(12), 1732–1739. https://doi.org/10.1016/S1470-2045(21)00528-3
Theelen, W. S. M. E., Peulen, H. M. U., Lalezari, F., van der Noort, V., de Vries, J. F., Aerts, J. G. J. V., Dumoulin, D. W., Bahce, I., Niemeijer, A.-L. N., de Langen, A. J., Monkhorst, K., & Baas, P. (2019). Effect of pembrolizumab following stereotactic body radiotherapy versus pembrolizumab alone on tumour response in patients with advanced non-small cell lung cancer: Results of the PEMBRO-RT phase 2 randomised clinical trial. JAMA Oncology, 5(9), 1276–1282. https://doi.org/10.1001/jamaoncol.2019.1478
Trentesaux, V., Maiezza, S., Bogart, E., Le Deley, M.-C., Meyer, E., Vanquin, L., Pasquier, D., Mortier, L., & Mirabel, X. (2024). Stereotactic body radiotherapy as a viable treatment for extracranial oligometastases in melanoma patients: A retrospective multicentre study. Frontiers in Oncology, 14, 1322515. https://doi.org/10.3389/fonc.2024.1322515
Wang, J. H., Sherry, A. D., Bazyar, S., Sutera, P., Radwan, N., Phillips, R. M., Deek, M. P., Lu, J., Dipasquale, S., Deville, C., DeWeese, T. L., Song, D. Y., Wang, H., Hobbs, R. F., Malek, R., Dudley, S. A., Greco, S. C., Antonarakis, E. S., Marshall, C. H., . . . Kiess, A. P. (2025). Outcomes of radium-223 and stereotactic ablative radiotherapy versus stereotactic ablative radiotherapy for oligometastatic prostate cancers: The RAVENS phase II randomised trial. Journal of Clinical Oncology, 43(18), 2059–2068. https://doi.org/10.1200/JCO-25-00131
Wang, X. S., Bai, Y. F., Verma, V., Yu, R. L., Tian, W., Ao, R., Deng, Y., Zhu, X.-Q., Liu, H., Pan, H.-X., Yang, L., Bai, H.-S., Luo, X., Guo, Y., Zhou, M.-X., Sun, Y.-M., Zhang, Z.-C., Li, S.-M., Cheng, X., . . . Zeng, M. (2023). Randomised trial of first-line tyrosine kinase inhibitor with or without radiotherapy for synchronous oligometastatic EGFR-mutated non-small cell lung cancer. Journal of the National Cancer Institute, 115(6), 742–748. https://doi.org/10.1093/jnci/djac015
Weichselbaum, R. R., & Hellman, S. (2011). Oligometastases revisited. Nature Reviews Clinical Oncology, 8(6), 378–382. https://doi.org/10.1038/nrclinonc.2011.44
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Copyright (c) 2026 Kinga Augustyniak, Franciszek Szweda, Tomasz Poczwardowski, Adrianna Kaczmarek, Katarzyna Anna Kowalska, Jakub Tomasz Latos, Marcin Chwalczuk, Olivia Grygorcewicz, Marta Koneczna, Karolina Alicja Krystyniak
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