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Management of Advanced Solid Tumors Recurring After Adjuvant Immune Checkpoint Inhibitors: A Structured Narrative Review
1
Oncology Unit, ASST Bergamo Ovest, 24047 Treviglio, Italy
2
Oncology Unit, Casa di Cura Igea, 20144 Milano, Italy
3
Oncology Unit, ASST Papa Giovanni XXIII, 24127 Bergamo, Italy
*
Authors to whom correspondence should be addressed.
Curr. Oncol. 2026, 33(9), 512; https://doi.org/10.3390/curroncol33090512
Submission received: 19 July 2026
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Revised: 22 August 2026
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Accepted: 26 August 2026
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Published: 27 August 2026
Simple Summary
When cancer returns after immune checkpoint inhibitor treatment given around curative surgery, clinicians often have little direct evidence to guide the next therapy. This review examines melanoma, non-small-cell lung cancer, renal cell carcinoma, urothelial carcinoma, and triple-negative breast cancer. A short interval to recurrence is consistently associated with poorer outcomes, but it does not identify one resistance mechanism or reliably predict benefit from a specific treatment. Decisions should also consider tumor type, disease extent and sites, molecular findings, previous immune-related toxicity, comorbidities, patient preference, and treatment access. Direct post-adjuvant evidence is strongest in melanoma and remains limited in the other tumors. We therefore propose uniform timing definitions, an explicit hierarchy separating direct evidence from extrapolation, and tumor-specific rather than universal rules for checkpoint inhibitor re-exposure.
Abstract
Adjuvant and perioperative immune checkpoint inhibitors (ICIs) have created a growing population of patients who relapse after prior programmed death-1 or programmed death-ligand 1 blockade, yet these patients were underrepresented in many trials that established metastatic standards. We performed a structured narrative review of PubMed/MEDLINE, ClinicalTrials.gov, reference lists, and international oncology guideline repositories through 15 August 2026. Eligible reports addressed recurrence patterns or treatment after curative-intent ICI in melanoma, non-small-cell lung cancer (NSCLC), renal cell carcinoma (RCC), urothelial carcinoma, or triple-negative breast cancer (TNBC); landmark metastatic studies were included only when direct evidence was unavailable and are labeled as extrapolation. Timing was standardized as on-treatment recurrence, early off-treatment recurrence (after the last ICI dose through 12 months), and late recurrence (>12 months). Shorter disease-free interval is consistently prognostic, but treatment-by-timing interactions are rarely available; timing should not be described as a validated pan-tumor predictive biomarker. Direct post-adjuvant evidence supports switching away from anti-PD-1 monotherapy for melanoma recurring on treatment, while selected late relapses may retain sensitivity. In RCC, retrospective post-adjuvant data support VEGF-targeted options, whereas CONTACT-03 and TiNivo-2 discourage routine ICI-TKI rechallenge specifically after prior ICI-treated metastatic RCC. Evidence in NSCLC, urothelial carcinoma, and TNBC is largely indirect. IMpassion132 was not an ICI-rechallenge trial, and only a small minority of ASCENT-04 participants had prior perioperative ICI. Treatment should integrate tumor-specific biology, actionable alterations, recurrence distribution, prior toxicity, comorbidity, access, and patient preference. Prospective trials dedicated to post-adjuvant ICI recurrence are needed.
