A djuvant immune checkpoint inhibition (CPI) and BRAF/ MEK-targeted therapies after therapeutic lymph node dissection (TLND) have improved relapse-free survival (RFS) in patients with clinical stage III nodal melanoma. Despite these improvements, approximately 40-50% of patients have a relapse within 3-5 years after TLND 1-3 . Preclinical and early clinical trial data suggest that neoadjuvant CPI leads to superior anti-tumor immunity and survival benefit compared to adjuvant CPI 4,5 . Similarly to stage IV melanoma, the combination of anti-CLTA-4 and anti-PD-1 appears to be superior to anti-PD-1 monotherapy in the neoadjuvant setting 6,7 . Previous clinical trials (OpACIN (NCT02437279) and OpACIN-neo (NCT02977052)) testing neoadjuvant ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) in stage III melanoma demonstrated high pathologic response rates (pRRs; 74-78%) and a strong association between pathologic response and RFS, with 94-100% of responding patients remaining free of relapse at 2 years 5,7-9 . Similarly, long-term benefit was observed upon complete response to CPI in stage IV melanoma, even after cessation of CPI [10][11][12] .The association between response and survival; the observed ongoing responses after cessation of therapy in stage IV melanoma; and the substantial morbidity from TLND [13][14][15][16] that impairs

Health-related quality of life in stage III melanoma patients treated with neoadjuvant ipilimumab and nivolumab followed by index lymph node excision only versus therapeutic lymph node dissection: 24-week results of the PRADO trial

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10064 Background: Neoadjuvant ipilimumab and nivolumab induces high pathologic response rates of 74-78% (OpACIN and OpACIN-neo trial), thus the role of Therapeutic Lymph Node Dissections (TLND) in patients with major pathologic responses (MPR: pathological (near) complete response) is now unclear. In the PRADO trial, TLND was omitted in patients with MPR in their index lymph node ((ILN), the largest LN marked prior to neoadjuvant therapy). We sought to determine if less extensive surgery is associated with better Health Related Quality of Life (HRQoL). These are the first results of the comparison of HRQoL between patients undergoing a TLND or less extensive ILN excision. Methods: HRQoL was assessed with the European Organisation for Research and Treatment of Cancer QoL questionnaire-C30 (QLQ-C30). A generalized estimation equation was used to assess the difference in HRQoL outcomes between patients who underwent TLND (pathological non- and partial-responders, pNR/pPR) versus those who did not (pathological (near)complete responders, pNCR/pCR). Differences were adjusted for age, gender and follow-up (FU, in weeks), but not for pathological responses (pNR, pPR, pNCR & pCR). Differences in QLQ-C30 scores were classified as clinically important according to published guidelines. Results: A total of 49 patients from the PRADO study had reached at least 24 weeks FU, and were included in the first explorative analysis. The median age of this study population was 58 years (range, 22-84). Questionnaire completion rates were high: 94% at baseline, 100%, 90%, 88% at week 6, 12 and 24, respectively. Sixteen (33%) patients underwent TLND versus 33 (67%) who had ILN excision only. Over a FU period of 24 weeks, patients who underwent TLND scored significantly lower on global (68 vs 78, adjusted difference (diff) = -9.53, p = .005), physical (84 vs 94 diff = -11.1, p = < .001), emotional (69 vs 83, diff = -11.7, p = .001), role (70 vs 85, diff = -13, p = .004), and social functioning (81 vs 91, diff = -8.9, p = .016) and had a higher symptom burden of fatigue (35 vs 23, diff = 11.1, p = .004), insomnia (38 vs 18, diff = 16.6, p = .002) and financial impact (12 vs 4, diff = 7.9, p = .027) than patients undergoing ILN excision only. These differences were indicated as clinically relevant. Conclusions: First results from PRADO suggest that reducing the extent of surgery following neoadjuvant immunotherapy might result in better HRQoL of high-risk stage III melanoma patients. Clinical trial information: NCT02977052.

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