Loading ...

TOPLINE: 

Serial metastasis-directed radiotherapy extended time off systemic therapy while maintaining favorable progression-free and overall survival in patients with oligometastatic clear-cell renal cell carcinoma (RCC). Circulating tumor DNA (ctDNA) combined with clinical factors may help in patient selection.

METHODOLOGY: 

• Oligometastatic clear-cell RCC is typically managed with systemic therapy, which incurs high costs, frequent clinic visits, and significant side effects. De-escalation with metastasis-directed radiotherapy may delay systemic treatment and reduce these burdens, but evidence on its effectiveness and patient selection is limited.
• Researchers conducted a single-arm, phase 2 trial of 121 patients with histologically confirmed clear-cell RCC and 1-5 metastases, most commonly in the lungs and lymph nodes. Patients received metastasis-directed radiotherapy to all disease sites, with additional therapy allowed for limited progression. The most common radiation fractionation schedule was 40-50 Gy in four fractions (n = 59).
• The co-primary endpoints were progression-free survival (PFS) and systemic therapy-free survival (STFS) (defined as the interval from enrollment to initiation of systemic therapy or death from RCC).
• The secondary endpoints were overall survival (OS), freedom from new lesion progression, and grade 2 or higher treatment-related adverse events. Median follow-up was 36.3 months.

TAKEAWAY:

• The median STFS was 34 months, exceeding the prespecified 24-month threshold for success. One-year PFS was 67.5 %, and median PFS was 17.7 months.
• OS was 96.7% at 1 year and 86.5% at 3 years, with median OS not reached — comparing favorably with past studies of similar patient populations. The rate of freedom from new-lesion progression was 72.7% at 12 months, with a median time to new-lesion progression of 22.7 months.
• In an exploratory analysis of prognostic factors, the number of metastatic lesions and number of prior systemic therapy lines w ere independently associated with STFS. Similarly, baseline ctDNA positivity was linked to shorter STFS compared to ctDNA negativity (28.1 vs 54.1 months; hazard ratio [HR], 2.75; P = .0064), while 3-month ctDNA positivity predicted shorter survival (19.1 vs 49.9 months; HR, 4.42; P < .0001). This suggests ctDNA combined with clinical factors could help select patients most likely to benefit from metastasis-directed therapy, the authors wrote.
• Eight patients (7%) experienced grade 3 or 4 adverse events, including back pain, leukocytosis, abdominal distension, buttock pain, fracture, hepatobiliary blockage, and pleural effusion.

IN PRACTICE:

"The current trial demonstrates that serial metastasis-directed therapy in patients with oligometastatic clear-cell renal-cell carcinoma can extend the interval off systemic therapy while maintaining favourable progression-free survival and overall survival with limited toxicity," the authors wrote. While ctDNA-based patient selection requires further validation, they add, "these findings highlight the potential for personalised, systemic therapy sparing strategies to optimise outcomes, while minimising treatment-associated toxicities and healthcare costs."

SOURCE:

The study, led by Chad Tang, MD, The University of Texas MD Anderson Cancer Center, Houston, was published online in The Lancet Oncology.

LIMITATIONS:

Findings are based on a single-institution, nonrandomized design. Additionally, quality-of-life metrics were not evaluated, and systemic therapy initiation was subject to patient and physician discretion despite specified protocol criteria. 

DISCLOSURES:

The study received support from the Cancer Prevention and Research Institute of Texas, the US National Cancer Institute, and Myriad Genetics, which provided ctDNA results. Tang disclosed serving on advisory boards for Bayer, Lantheus, and Telix; receiving honoraria from Elekta, consulting fees from Boston Scientific; royalties from Wolter Kluwer; and research support from Myriad Genetics and Merck. Four authors declared being employees of Myriad Genetics and receiving stock as part of their compensation. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.