Thirty years of adjuvant therapy: From treating risk to treating residual disease.

Abstract

Over the past three decades, adjuvant therapy for solid tumours has evolved from treatment based predominantly on anatomical recurrence risk towards strategies informed by tumour biology, treatment response, and molecular residual disease. Cytotoxic chemotherapy and endocrine therapy established the curative potential of postoperative systemic treatment, while targeted agents and immunotherapy expanded its efficacy across malignancies. However, matching a drug to tumour biology does not establish whether residual cancer remains, and many patients receive treatment despite having been cured by surgery alone. This Perspective examines the transition from empirical risk reduction towards selective intervention against residual disease. Response-adapted perioperative strategies provide a dynamic assessment of treatment sensitivity and support postoperative escalation or omission in defined settings. Circulating tumour DNA offers a complementary approach, but its strong prognostic value must be distinguished from evidence that biomarker-directed treatment improves outcomes. Contrasting findings from randomised trials demonstrate that neither de-escalation after a negative result nor escalation after a positive result can be generalised across clinical contexts. Future studies should integrate anatomical risk, tumour genomics, pathological response, and longitudinal molecular assessment while prioritising absolute benefit, mature survival outcomes, irreversible toxicity, patient-reported outcomes, and equitable access. They should also distinguish durable eradication from temporary suppression and evaluate treatment omission with the same rigour as intensification. Progress in adjuvant oncology should ultimately be measured by additional cures achieved with less avoidable harm, through the smallest effective intervention supported by validated evidence.