Decision regret and toxicity perception following adjuvant pembrolizumab in renal cell carcinoma.

Abstract

4512 Background: Adjuvant pembrolizumab (pembro) is standard of care in renal cell carcinoma (RCC). We explored whether patients retrospectively regret their decision to receive adjuvant pembro and hypothesised that this is related to long-term toxicity that is not adequately captured by CTCAE criteria. To address this we developed a patient-informed tool, co-designed with patients, focusing specifically on long-term toxicity. Methods: Patients with RCC who received adjuvant pembro across three tertiary cancer centres in London between June 2022-Dec 2024 were invited to participate. Eligible patients completed the validated Ottawa Decision Regret Scale (DRS) and a complementary questionnaire exploring factors influencing regret including toxicity and disease recurrence. CTCAE-graded immune-related adverse events (irAEs) were collected and correlated with decision regret (DR). In parallel, patients categorised irAEs as life-changing, significant or non-significant and these were correlated with DR. DRS > 25 was defined as moderate-high regret. Appropriate ethical approval was obtained. Results: 104 patients were included post adjuvant pembro (88% pT3N0, 4% pT3N1 and 8% M1 NED). Median follow up was 30 months. 14% patients have relapsed. CTCAE ≥G3 irAEs occurred in 18%. 28% and 11% reported toxicity as significant (S) or life changing (LC) respectively. Patient reported S and LC toxicity did not correlate with ≥G3 CTCAE ( p = 0.11), with 33% CTCAE G1-2 events reported as significant. Mean DR score was 14.9 (95% CI 8.5-21.3) with 13% expressing regret. 1/14 patients who had disease recurrence expressed regret (mean DRS = 10.3 [1.4-19.3]). Patients that reported LC & S toxicity expressed more regret (26.9 LC v 26.1 S v 2.1 NS, p = 0.0021). There was no difference in regret between patients that sustained CTCAE G1-2 versus G3-4 irAE (14.9 vs 15.1, p = 0.23). DR was highest with permanent endocrine (n = 24) or musculoskeletal (n = 22) irAEs (endo: DRS 28.8 v 9.5, p = 0.003; MSK: DRS 25.1 v 12.8, p = 0.042). Lower baseline expectations of toxicity correlated with greater DR ( p = 0.002). Conclusions: DR after adjuvant pembro is driven by long-term, low-grade toxicity rather than disease recurrence. Novel patient-informed tools that capture life-changing or permanent toxicities outperform CTCAE in identifying patients at risk of regret. Improved baseline education on long-term risks may reduce decision regret and improve shared decision-making.