Based on recently published phase II/III studies, we found that individuals with OMD receiving aggressive local treatment survived an excess of 7.9–15 months and survived without disease progression, between 4.6 and 11.1 months, on average.

In the setting of OMD, SBRT as means of MDT has been endorsed as a standard-of-care treatment [14, 15]. Its main indications include residual disease after systemic treatment, cases unsuitable for surgery, or oligo-progressive disease [16, 17]. Historically, most data supporting this concept was based on single-arm studies [6]. A small number of RCTs have been conducted to examine this hypothesis. ORIOLE, and STOMP were phase II trials evaluating the addition of SBRT to all disease sites in oligometastatic prostate cancer. ORIOLE demonstrated an improved median PFS (mPFS) (not reached vs. 5.8 months, p = 0.002), and STOMP showed an improved median bRFS (10 vs. 6 months, p = 0.03), in favor of the intervention groups [4, 18, 19]. Three trials examined the effect of MDT in non-small cell lung cancer (NSCLC) patients. Gomez et al. and Iyengar et al. investigated the role of local consolidative RT in patients without progression after front-line systemic treatment. Both trials were terminated early due to significantly prolonged mPFS in the treatment arm (Gomez et al.: 14.2 vs. 4.4 months, p = 0.022; Iyengar et al.: 9.7 vs. 3.5 months, p = 0.01) [20, 21]. The sample size of SINDAS was the largest, with 133 NSCLC patients receiving first-line tyrosine kinase inhibitors. The SBRT-treated group achieved a significantly improved mPFS (20.2 vs.12.5 months, p < 0.001) and median OS (25.5 vs. 17.4 months, p < 0.001).

The oligometastatic state is considered independent of the type of the primary tumor [22]. However, its indiscriminate adoption may be inappropriate considering the heterogeneity of various OMDs. For example, contrary to the positive results of the SINDAS trial that examined the effect of MDT consolidation in the setting of EGFR-mutated NSCLC, the NRG-BR002 trial, which tested the effect of local consolidation in oligometastatic breast cancer patients, found no significant difference in PFS or OS [23].

Omission of systemic therapy should be considered with caution in highly selected patients, as solely treating the overt metastatic lesions could compromise outcomes in certain malignancies. SABR-COMET compared systemic SOC therapy with or without the addition of SBRT [4]. SINDAS enrolled patients with EGFR-mutated NSCLC who responded to systemic therapy and then received local consolidation [24]. The accruing phase III SABR-COMET 3 and 10 studies, would further assess the impact of SBRT in addition to systemic therapy in patients with up to 3 or 10 metastatic lesions, respectively [2, 3]. Conversely, STOMP and ORIOLE excluded patients who initiated androgen deprivation therapy.

Aggressive local therapy with SBRT is associated with durable disease control owing to low rates of local failure [18]. However, the treatment carries a risk for serious side effects. A meta-analysis of prospective trials evaluating SBRT in oligo-metastatic patients demonstrated acute grade 3–5 toxicity rates between 0% and 20% and late grade 3–5 toxicity between 0% and 10% [6]. While it is perceived to be potentially curative in patients with a limited number of metastatic lesions, long-term data is lacking. Hence, the current therapeutic goal should be prolonged OS and improved QoL. It is imperative to highlight treatment objectives to patients and confirm compatibility with their wishes. In cases where long-term PFS or potential cure is pursued, patients may be willing to accept a risk for severe toxicity that could be associated with long-term detrimental effects on their QoL. However, when the objective is palliative, any intervention must be meticulously scrutinized.

Compared with the limitations of the HR and the potential misleading interpretation of the median, while less familiar, the RMST difference is a robust and intuitive measure of outcomes. It can be explained as the average time benefit from the proposed treatment subject to the follow-up period. Some trials, such as SINDAS, yielded comparable estimates, with RMST and median OS calculated at 7.9 and 7.4 months, respectively. Nonetheless, while the median indicates the chances of surviving 7.4 months are as likely as not, it does not provide information about the expected survival time which is provided by RMST with 7.9 months. Further, RMST is more stable and precise due to narrower confidence interval than that of the median [10]. For other trials, the median and RMST estimates differed substantially without any significant correlation to the HR. Notably, the RMST for PFS analysis of SABR-COMET and bRFS analysis of STOMP suggested a median benefit that is underestimated by more than two-fold, with absolute difference of 5.7 and 4.3 months, respectively. In contrast, the RMST for OS analysis of SABR-COMET and Gomez et al. implied an overestimated median survival benefit with an absolute difference of 9.7 and 5.5 months, respectively. Furthermore, the difference in mPFS was not estimable in ORIOLE as the median for the SBRT group was not reached, which restricts the clinical interpretability of the outcome. Contrarily, the RMST difference was estimated to be 6.2 months. Unlike the HR or median, the RMST consistently results in clinically interpretable summaries of the treatment effect.

RMST has been gaining recognition for its utility in survival analysis and is increasingly employed for reporting study outcomes within the literature [25,26,27], major oncology conferences [28, 29], and support the approval of drugs by the FDA [30,31,32]. Serving as either a complimentary metric or alternative to the HR, RMST can be used to describe clinical endpoints such as OS and PFS. Notably, when RMST is reported it is often used when the PH assumption is not met.

Although the conventional measures HR and median have their benefits, RMST can serve as a robust alternative for both metrics, even when the PH assumption holds. The distinct advantages of the RMST lie in its capacity to provide a single, precise, model-free, clinically interpretable, time-scale summary of survival. However, no single summary measure may always adequately characterize the results. Given that clinical trialists customarily report HR and median, we fill it is instructive to compare these with RMST, even when the PH assumption is satisfied. Conversely, when the PH assumption is violated, RSMT should substitute HR as a summary measure and prespecified in the study protocol.

The limitations of this study include the reliance on small, mostly phase II trials, which may not be thoroughly applicable to larger populations. Additionally, there is a high degree of variation between the studies in terms of patient characteristics, prognosis of the primary disease, endpoints, and follow-up time. The former can make interpretation of the results challenging. Although our main goal was to analyze local treatment of OMD with RT, some studies included both surgery and RT, leading to potential selection bias between these two modalities. Notably, surgery remains the main modality for some indications, such as oligometastatic liver disease in colorectal cancer [33]. Furthermore, only three studies reported on OS, providing a limited view of the gold standard, most significant endpoint in establishing clinical benefit. Additionally, the use of RMST as a measure of treatment efficacy, similarly to HR, is follow-up time-dependent and may lead to over- or underestimation of the effect. Furthermore, any survival analysis is based on the assumption of uninformative censoring, which can affect the validity of the results [34,35,36]. In addition, the study did not evaluate the statistical robustness of the results [37].