In an international validation study reported in the Journal of Clinical Oncology, El Sissy et al found that the Immunoscore biopsy was capable of distinguishing risk of disease recurrence in patients with rectal cancer treated with a watch-and-wait strategy.
As stated by the investigators, “No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait strategy is currently available. Prognostic performance of the Immunoscore biopsy was recently suggested in a preliminary study.”
Study Details
The study included 249 patients with initial biopsies of stage I to III rectal cancer who had clinical complete response after neoadjuvant therapy and who were managed by a watch-and-wait strategy at sites in six countries between 1989 and 2020. Intratumoral CD31 and CD81 T cell densities in pretreatment biopsies were converted into percentiles, and mean percentiles were translated into Immunoscore biopsy categories: low = 0% to 25%, intermediate = > 25% to 70%, and high = > 70% to 100%. The primary outcome measure was time to recurrence—the time from end of neoadjuvant treatment to the date of local regrowth or distant metastasis.
Key Findings
Recurrence-free rates at 5 years were 91.3% (95% CI = 82.4%–100.0%) in Immunoscore biopsy–high patients, 62.5% (95% CI = 53.2%–73.3%) in Immunoscore biopsy–intermediate patients, and 53.1% (95% CI = 42.4%–66.5%) in Immunoscore biopsy–low patients (hazard ratio [HR] for low vs high = 6.51, 95% CI = 1.99–21.28, P = .0004; HR for intermediate vs high = 4.3, 95% CI = 1.3–14.0, P = .0078; P for trend = .0006). The hazard ratio for local regrowth for Immunoscore biopsy–low vs Immunoscore biopsy–high patients was 6.3 (95% CI = 1.9–20.7, P for trend = .0004); the hazard ratio for distant metastasis for Immunoscore biopsy–low vs Immunoscore biopsy–high patients was 6.7 (95% CI = 0.87–51.7, P for trend = .029).
Immunoscore biopsy category was also significantly associated with disease-free survival. The hazard ratio for Immunoscore biopsy–intermediate vs Immunoscore biopsy–high was 4.6 (95% CI = 1.4–14.7, P = .005), and the hazard ratio for Immunoscore biopsy–low vs Immunoscore biopsy–high was 7.6 (95% CI = 2.3–24.6, P < .0001).
On multivariate analysis, Immunoscore biopsy was independent of patient age, sex, tumor location, clinical T stage, and clinical N stage, and was the strongest predictor of time to recurrence (HR for Immunoscore biopsy–low vs Immunoscore biopsy–high = 6.93, 95% CI = 2.08–23.15, P = .0017).
The investigators concluded, “The Immunoscore biopsy is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.”
Franck Pagès, MD, PhD, of the Department of Immunology, European Georges Pompidou Hospital, Paris, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by l’Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation ARC Association pour la Recherche contre le Cancer, and others. For full disclosures of the study authors, visit ascopubs.org.
