ESTRO 2026 Congress Report

By the Oligometastatic Disease Focus Group

 

Results of the randomised phase-II trial of the use of stereotactic body radiotherapy with or without darolutamide for oligorecurrent prostate cancer (DART)

 

Piet Ost from Belgium presented the results of the DART trial, in which researchers investigated whether the addition of six months of darolutamide, a next-generation androgen receptor pathway inhibitor (ARPI), to stereotactic body radiotherapy (SBRT) could improve outcomes in patients with oligorecurrent prostate cancer. The rationale was based on the favourable toxicity profile of ARPIs compared with conventional androgen deprivation therapy (ADT), with fewer hot flushes and less impact on sexual function, although gynaecomastia and breast pain occur more frequently.

Eligible patients had biochemical recurrence after primary treatment, a doubling of the level of prostate-specific androgen (PSA) in fewer than 12 months, testosterone levels above 50ng/ml, and oligometastatic disease that was detected exclusively by prostate-specific membrane antigen (PSMA) PET imaging. Unlike in earlier studies such as the consideration of surveillance or treatment of metastasis in prostate cancer (STOMP) and observational research in metastatic lesions of the endocrine/prostate (ORIOLE), all recurrences were distant metastases that had been identified using modern molecular imaging. Patients were randomised to receive either SBRT alone or SBRT combined with six months of darolutamide. The primary endpoint was metastasis-free survival (MFS), which was assessed using serial PSMA PET imaging during follow-up. The study was powered to detect a hazard ratio of 0.54 in favour of the combination arm.

Baseline characteristics reflected the early detection that is enabled by PSMA PET imaging. Median PSA was low at 1.6ng/ml, consistent with earlier detection of recurrence, while PSA doubling times were short, with median values of 4.4 months in the SBRT arm and 3.9 months in the SBRT plus darolutamide arm, indicating biologically aggressive disease. Most metastatic lesions were located in bone (more than 60%), whereas non-regional lymph nodes accounted for 30% of lesions. Although most patients presented with a single metastatic lesion, more than one-third had two or more targets treated.

The addition of darolutamide resulted in a PSA response in 100% of patients, compared with 17% in the SBRT-only arm. However, this biochemical effect did not translate into significant improvements in clinically relevant outcomes. Rates of biochemical recurrence-free survival, clinical recurrence-free survival, and the primary endpoint of metastasis-free survival were not significantly different between treatment arms. Across endpoints, the combination strategy appeared to delay progression by approximately six months, and this corresponded to the duration of darolutamide administration, after which the survival curves rapidly converged. Notably, at progression, around 90% of patients developed only one or two new lesions.

Treatment was generally well tolerated. Darolutamide was associated with higher rates of skin rash, diarrhoea, fatigue, and gynaecomastia, but no grade-3 adverse events were attributed to the drug. Quality of life remained largely preserved, with only transient impairments observed during the six-month darolutamide treatment period, mainly related to hot flushes and gynaecomastia.

Overall, the DART trial showed that treatment with darolutamide delayed disease progression only during the treatment period, without producing a sustained benefit after treatment discontinuation. No synergistic effect between darolutamide and SBRT was demonstrated in this study.

 

Metastasis-directed treatment in patients with oligometastatic breast cancer: results from the OLIGOMA trial

As discussed in another article in this newsletter, David Krug presented the results of the OLIGOMA trial, a randomised study in which metastasis-directed treatment (MDT) with stereotactic body radiotherapy (SBRT) was evaluated in patients with oligometastatic breast cancer. Previous randomised trials in this setting, including that led by NRG Oncology (NRG-BR002) and that into the use of external beam radiation to eliminate nominal metastatic disease (EXTEND), had not demonstrated progression-free survival (PFS) benefit with the addition of SBRT to standard systemic therapy.

In the OLIGOMA trial, patients with oligometastatic breast cancer (≤5 lesions, including locoregional recurrence and up to three brain metastases) were randomised to receive either systemic therapy alone or systemic therapy combined with SBRT to all metastatic lesions. Systemic treatment was determined before enrolment, and randomisation was stratified according to systemic treatment type and treatment line. The co-primary endpoints were PFS and quality of life (QoL), which was assessed through use of the European Organisation for the Research and Treatment of Cancer QoL questionnaire core 30 (QLQ-C30) 12 weeks after randomisation. Secondary endpoints included overall survival (OS), toxicity, compliance, QoL, and patient satisfaction with cancer care.

A total of 87 patients were randomised. The median age was 58 years, and most patients had an Eastern Cooperative Oncology Group performance status of zero (76.7% in the experimental arm versus 61.4% in the control arm). Most cases were hormone-receptor positive (76.6% versus 81.8%), whereas fewer were human-epidermal-growth-factor-receptor 2 (HER2) positive (7.5% versus 15.0%) or involving triple-negative tumours (12.5% versus 11.4%). Approximately half of the patients were receiving first-line systemic treatment; hormonal therapy was being used in around two-thirds of patients and was combined with a cyclin-dependent-kinase 4/6 inhibitor in 50%. Nearly half (46%) had synchronous metastases. More than 80% of patients presented with one to three metastatic lesions, and bone metastases accounted for approximately two-thirds of cases in both treatment arms. The median SBRT schedule consisted of five fractions with a total dose of 40Gy. Median follow-up was 26 months.

The median PFS was 35.8 months in the SBRT arm versus 20.4 months in the control arm (HR 0.48, 95% CI 0.25-0.91; p=0.021). Progression of initial metastases and the appearance of new metastases occurred less in the experimental than in the control arm (11.6% versus 27.3% and 25.6% versus 40.9%, respectively). The QoL co-primary endpoint met the predefined non-inferiority criterion with the addition of SBRT. Serious adverse events occurred in 15% of patients in both groups, with only one event considered treatment-related. OS data are currently immature.

OLIGOMA is the first randomised controlled trial to have demonstrated a PFS benefit from MDT in patients with oligometastatic breast cancer, while maintaining short-term QoL. A major limitation of the study was the premature closure of recruitment, with accrual stopping at less than 20% of the initial planned sample size and less than 40% of the amended sample size. Despite these positive results, further prospective trials are necessary to better identify the patient populations that are most likely to benefit from MDT.

 

 

Nicolas Martz, MD

Radiation oncologist

Institut de Cancérologie de Lorraine

Nancy, France

Core member of the Oligometastatic Disease Focus Group