Reconsidering adjuvant and perioperative immune-checkpoint inhibition: de-escalation, expansion and personalization.

This article is a narrative review on the evolving role of anti–PD-L1 antibodies in early-stage solid tumors, focusing on melanoma, renal cell carcinoma, and non–small-cell lung cancer.

Key points:

• Rationale for early use: Moving PD-L1 blockade from metastatic to adjuvant, neoadjuvant, or perioperative settings can reduce the risk of metastatic relapse and may improve long-term outcomes. Pathologic and event-free survival benefits are clearer than overall survival benefits so far, partly because of limited follow‑up and effective use of PD‑(L)1 therapy at recurrence.
• Evidence to date: Early-stage trials show that earlier introduction of anti–PD-L1 agents can yield meaningful reductions in recurrence risk. However, consistent overall survival benefit across tumor types and settings is not yet proven, and interpretation is complicated by subsequent lines of immunotherapy at relapse.
• Adjuvant vs neoadjuvant/perioperative: Emerging data suggest neoadjuvant or perioperative strategies may be superior to purely adjuvant use in some cancers, likely due to intact tumor antigen exposure, more robust priming of systemic immunity, and better early assessment of response (e.g., pathologic response).
• De-escalation strategies: The authors discuss:
  • • Shortening adjuvant treatment duration.
  • • Deferring anti–PD-L1 therapy until recurrence rather than giving it to all high‑risk patients upfront.
  • • Shifting from mandatory monotherapy to reserving combination approaches (e.g., with other systemic agents) for the metastatic or recurrent setting.
• Refining indications and combinations: They highlight:
  • • Expansion of indications within specific tumor types (e.g., higher‑risk early-stage subgroups) where recurrence risk is substantial.
  • • Greater emphasis on biomarker-defined populations to enrich for benefit.
  • • Rational combinations in the perioperative window to maximize cure while preserving tolerability.
• Biomarker-guided personalization: Circulating tumor DNA and other emerging assays are discussed as tools to:
  • • Identify minimal residual disease.
  • • Stratify recurrence risk.
  • • Guide initiation, continuation, or early discontinuation of therapy.
  • • Potentially distinguish patients who need intensified perioperative strategies from those suitable for de-escalation.

Overall, the review frames early-stage use of anti–PD-L1 antibodies as moving from a “treat-all high-risk patients” paradigm toward a more nuanced, biomarker- and timing-driven approach, with increasing emphasis on neoadjuvant/perioperative strategies and treatment tailoring to balance cure potential, toxicity, and resource use.