Background C-POST is a phase 3, double-blind, multicenter, placebo-controlled trial (NCT03969004) of adjuvant cemiplimab for the treatment of CSCC with high risk of recurrence after surgery and radiation therapy. We present the primary analysis including efficacy, safety, and PROs. Methods C-POST included patients with local and/or regional CSCC after surgery and post-operative radiation therapy, at high risk of recurrence based on nodal and/or non-nodal criteria. Patients were randomized 1:1 to cemiplimab 350 mg or placebo Q3W for 12 weeks, then cemiplimab 700 mg or placebo Q6W up to 36 weeks (up to 48 weeks total). Crossover was allowed after disease recurrence. The primary endpoint was disease-free survival (DFS). Secondary endpoints included freedom from local-regional recurrence (FFLRR), freedom from distant recurrence (FFDR), overall survival (OS), and safety. The pre-specified PRO analysis focused on QLQ-C30 global health status/quality of life (GHS/QoL), functional (physical, role, emotional), and symptom (fatigue, pain) scales. Overall PRO changes from baseline across treatment cycles were analyzed using mixed-effects models for repeated measures. The PRO responder analysis used a 10-point threshold for clinically meaningful change. The data cutoff (~50% of final DFS events; pre-specified threshold) was October 4, 2024. Results From June 2019 to August 2024, 415 patients (209/206 cemiplimab/placebo) were randomized: median age, 71 years (range 33–95); 83.9% male; 82.7% head and neck primary; 58.3%/41.7% high-risk nodal/non-nodal categories. Median (range) follow-up was 24 (2–64) months. DFS was superior with cemiplimab versus placebo (24 vs 65 events). Median DFS was not reached in the cemiplimab arm and was 49.4 months in the placebo arm; HR 0.32 (95% CI: 0.20–0.51; P<0.0001). Kaplan–Meier estimated 24-month DFS was 87.1% (95% CI: 80.3–91.6) for cemiplimab and 64.1% (95% CI: 55.9–71.1) for placebo. Cemiplimab improved FFLRR (HR 0.20; 95% CI: 0.09–0.40) and FFDR (HR 0.35; 95% CI: 0.17–0.72) versus placebo. Kaplan–Meier estimated 24-month FFLRR/FFDR was 94.6% (95% CI: 89.1–97.3)/94.3% (95% CI: 89.0–97.1) for cemiplimab and 76.7% (95% CI: 69.1–82.6)/83.8% (95% CI: 76.3–89.0) for placebo. OS HR (April 2025 data cutoff; 33 deaths) for cemiplimab versus placebo was 0.78 (95% CI: 0.39–1.56). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 23.9% and 14.2%, and discontinuations due to TEAEs occurred in 9.8% and 1.5% of patients receiving cemiplimab and placebo, respectively. Overall changes from baseline on QLQ-C30 GHS/QoL, functioning, and symptom scores were small and similar between arms. Most patients in both arms reported maintenance or clinically meaningful improvement in QoL in all scales across all cycles (cemiplimab: 55.9–86.8%; placebo: 55.5–88.2%). Kaplan–Meier estimated median time to first deterioration in QoL was similar between arms in all scales (cemiplimab: 5.6–25.6 months; placebo: 8.3–22.2 months). Conclusion Cemiplimab is the first systemic adjuvant immunotherapy to demonstrate statistically significant and clinically meaningful reduction in disease recurrence for high-risk CSCC, and was consistent with the known safety profile of cemiplimab monotherapy in advanced or metastatic disease. QoL was maintained on cemiplimab, with no clinically meaningful differences versus placebo.

PURPOSE:Unilateral radiation therapy (URT) is an effective treatment strategy in selected patients with lateralized tonsil cancer. However, there is a lack of established planning guidelines for URT treatment, leading to suboptimal optimization of contralateral and midline organs at risk (OARs). This study aimed to reoptimize URT plans to maximize sparing of midline and contralateral OAR's while maintaining target coverage, providing dosimetric guidelines for URT planning. METHODS AND MATERIALS:Treatment plan data for patients treated with URT on TROG 12.01 were reoptimized using Eclipse V16.01. All relevant midline and OAR contours were contoured to align with international OAR consensus guidelines. Treatment plans were reoptimized, aiming for maximal midline and contralateral sparing while maintaining TROG 12.01 protocol-mandated target coverage (gross tumor volume: D100% > 95%; planning target volume: D95% > 95%). A second reoptimization was performed to align with NRG acceptance criteria (planning target volume: D95% > 100%). RESULTS:All reoptimized plans achieved the TROG 12.01 and NRG protocol target volume coverage. Clinically meaningful reductions in dose to the pharyngeal constrictors (trial-delivered plan vs TROG reoptimized plan, median of mean dose, 48.5 Gy vs 37.4 Gy, estimated mean difference [ED] -9.5Gy, P < .001), contralateral submandibular gland (14.9 vs 6.7 Gy, ED -11.0, P < .001) and larynx (22.1 vs 12.1, ED -12.2, P < .001). Improvements were also seen in contralateral parotid gland (9.2 vs 4.9, ED -5.0, P < .001) and oral cavity (39.5 vs 35.9, ED -3.0, P < .001), which were considered less likely to be clinically relevant. There was no increase in dose to the ipsilateral or contralateral mandible. CONCLUSIONS:The results of this reoptimization study provide planning guidelines to guide dosimetrists and radiation oncologists on achievable OAR sparing when delivering URT.

BACKGROUND:Cutaneous T-cell lymphomas (CTCLs) are rare with distinct diagnostic challenges. Equitable access to cancer care is a recognized priority, internationally. To date, the geospatial distribution of CTCL has not been definitively studied. Understanding the incidence and geographical distribution of patients with CTCL are critical first steps towards the ultimate goal of equity of care. Geospatial analyses also allow the opportunity to explore environmental causative factors: for CTCL, the contribution of solar ultraviolet (UV) radiation on causation remains unclear. OBJECTIVES:We investigate geospatial patterns of CTCL incidence across Australia, compare with all rare cancers, and consider solar UV exposure on causality and diagnosis rates. METHODS:All CTCL diagnoses (1 January 2000 to 31 December 2019) were obtained from the nationwide dataset. Areas of residence were collected according to nationally approved definitions. Bayesian spatial incidence models were applied. Geospatial distributions were visually analysed. RESULTS:The CTCL age-standardised incidence rate was 7.7 (95% confidence interval 7.4-7.9) per million people per year in Australia. Diagnostic disparity was seen between Australian states/territories, with lower diagnosis rates in rural/remote and socioeconomically disadvantaged areas. Incidence exceeded the national average within more densely populated capital cities. Visual comparisons of the geospatial distribution of CTCL revealed marked discordances with the geospatial patterns of all rare cancers and solar UV in Australia. CONCLUSIONS:Geographical heterogeneity in CTCL exists across Australia. Incidence reflects population density. Geospatial patterns of CTCL differ substantially from all rare cancers, with implications for the unique diagnostic challenges and unmet needs of this patient population. The distribution of CTCL across Australia does not support a causative link with UV exposure. Further global evaluation of geospatial patterns is warranted.

Despite cutaneous squamous cell carcinoma (CSCC) being the second most common skin cancer worldwide, there were no approved systemic therapies for patients with unresectable and/or metastatic disease prior to the advent of anti-programmed cell death protein-1 (anti-PD1) agents cemiplimab and pembrolizumab [...]

Importance:Generic health utility instruments lack the discriminative ability to differentiate among health states in patients after head and neck cancer treatment. Objective:To develop, validate, and valuate a head and neck cancer-specific health utility measure. Design, Setting, and Participants:This psychometric study comprised 2 phases to develop and validate a health utility instrument. The first phase, development and validation, occurred from January 2021 to August 2022. An expert panel selected disease-specific quality-of-life instruments as the basis for a new utility instrument. Two datasets (n = 458 and 493) were used to establish dimension structure through exploratory factor analysis, and to select items using Rasch and psychometric criteria and expert opinion. Discriminative validity of the new instrument was tested by comparing scores for different disease severities (patients with and without gastrostomy and tracheostomy tubes). The second phase, valuation, was conducted from January 2023 to January 2024 in a quaternary referral center with healthy participants. Participants completed time-trade-off exercises for 100 sampled health states and were randomized to discovery and validation sets (80:20). Using a repeated measures model, a scoring algorithm to predict utilities of health states within the instrument was created in the discovery set and tested in both sets. Data were analyzed from January 2022 to December 2023. Intervention:Participants performed time-trade-off exercises for various states. Main Outcomes and Measures:Discriminative validity (first phase) and the mean absolute differences of predicted and observed utilities (second phase). Results:The European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire-Core 30 and its Head and Neck module 43 were selected by the expert panel and used as the basis instruments. Exploratory factor analysis established 8 dimensions, with 1 item selected per dimension. Of the 488 respondents, 84 with gastrostomy and/or tracheostomy tubes reported lower scores for 7 of the 8 items. In the second phase, 2497 valuations were performed by 250 healthy participants (mean [SD] age, 42.4 [16.5] years; 166 [66%] females). The scoring algorithm produced mean absolute differences between predicted and observed utilities of 0.041 (95% CI, 0.034-0.047) and 0.082 (95% CI, 0.065-0.100) in the discovery and validation sets, respectively. Conclusions and Relevance:This psychometric study developed a new head and neck cancer-specific utility measure, the HNC-8D (Head and Neck Cancer-8 Dimensions). The instrument demonstrated predictive accuracy for measuring health utility and can be used to differentiate health utility states following head and neck cancer treatment.

Antibodies against PD-1 (PD1i), such as cemiplimab and pembrolizumab, have demonstrated significant efficacy in advanced, unresectable cutaneous squamous cell carcinoma (cSCC). These agents elicit durable responses in approximately 45% of patients, contributing to improved aesthetic, functional, and survival outcomes in a subset of individuals with advanced cSCC. This review highlights recent and ongoing research investigating the safety and efficacy of immune checkpoint inhibitors for cSCC in the curative intent perioperative settings, advanced/metastatic setting, and within the immunocompromised patient populations.

Cutaneous T-cell lymphomas (CTCL) are a rare collection of diseases, frequently associated with diagnostic challenges and complex management dilemmas. The multidisciplinary team is vital for accurate clinico-pathological diagnoses and for collaborative therapeutic decisions throughout the management journey, which frequently involves multiple lines of therapy. Radiotherapy (RT) is a highly effective skin-directed therapy for CTCL, commonly delivered as localised fields or as total skin electron beam therapy (TSEBT). Mycosis fungoides (MF) is the most common of the CTCL, and patients typically experience high rates of morbidity and long natural histories of relapse and progression. Patients with MF typically present with incurable disease; in these patients, RT has an established role in symptom- and disease-control, achieving excellent response rates and proven therapeutic benefits. The role of RT continues to evolve, with modern practices favouring lower doses to reduce toxicity risks and allow for re-irradiation. Less commonly, there are situations where RT has an integral role in the potential cure of patients with MF: firstly, in the setting of unilesional MF where localised RT alone may be curative, and secondly, in the setting of preconditioning prior to curative-intent allogeneic hematopoietic stem cell transplant for patients with advanced MF/Sezary syndrome, where conventional-dose TSEBT is indicated as the most effective single agent for maximal debulking of skin disease. Radiotherapy also has an important role in the management of the less common CTCL, including the curative treatment of localised primary cutaneous anaplastic large cell lymphoma. Despite proven efficacy and quality of life benefits, disparity exists in access to RT and TSEBT. World-wide, stronger multidisciplinary collaborations and greater patient advocacy are required to increase access to RT and improve equity of care for our patients with CTCL.

The study's aim was to compare the unplanned admission rates and nutrition outcomes in patients with head and neck squamous cell cancer (HNSCC) receiving chemoradiotherapy at two different hospitals with different nutrition support approaches. Hospital Site A used prophylactic tube feeding and Site B used reactive tube feeding. Consecutive HNSCC patients receiving chemoradiotherapy with curative intent over six months in 2015 were eligible for this prospective comparative cohort study. Only patients who were classified as at high nutrition risk using validated guidelines were included. Patients' weight was recorded at the start, end, and 4-6 weeks post treatment to determine percentage weight loss outcomes. Unplanned hospital admissions (for medical or nutrition related reasons) and associated length of stay (LOS) were collected throughout and up to 1-month post treatment. In total, 88 patients were included in the study (site A n = 58; site B n = 30). The mean age was 60 years, 86-90% were male, and predominantly had oropharyngeal cancer. There was no statistical difference between the groups for percentage weight loss at any timepoint, rates of unplanned nutrition related admissions, or LOS. Stepwise logistic analysis showed that being of an older age was predictive of having an unplanned nutrition-related admission. In summary, there was no difference in the rate of unplanned admissions or percentage weight loss for patients with HNSCC managed under the prophylactic versus reactive tube feeding approach. Decision making regarding the choice of feeding tube should be made in consultation with the patient and the multidisciplinary team.

6065 Background: C-POST is a phase 3, double-blind, pbo-controlled trial (NCT03969004) of adjuvant cemi for treatment of patients (pts) with CSCC at high risk of recurrence after surgery and radiation therapy. Positive results for the primary endpoint of disease-free survival (DFS) at interim analysis 1 are reported in a separate ASCO abstract. Here we evaluate adjuvant cemi vs pbo on PROs as exploratory endpoints. Methods: Pts (N=415) were randomized 1:1 to adjuvant cemi or pbo for up to 48 weeks (4 cycles). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) was administered at Day 1 of every cycle, end of treatment, and during follow-up. The pre-specified PRO analysis focused on 6 QLQ-C30 scales of global health status (GHS)/QoL; 3 functional scales (physical [PF], role [RF], emotional [EF]); and 2 symptom scales (fatigue [FA], pain [PA]). Overall changes from baseline across treatment cycles were analyzed using mixed effects models for repeated measures; if 95% CIs did not cross zero, differences were considered of nominal statistical significance (α=0.05) as no adjustment was made for multiplicity. PRO responder analysis used a published threshold of 10 points for clinically meaningful change across scales; median time to first deterioration was determined using Kaplan–Meier analyses. Results: QLQ-C30 completion rates from baseline through all cycles were >88% in both arms. Baseline scores showed moderate-to-high GHS/QoL and functioning and low symptom burden (Table). Overall changes from baseline on QLQ-C30 GHS/QoL, functioning, and symptom scores were small and similar between arms (Table). In the PRO responder analysis, most pts in both arms reported maintenance or clinically meaningful improvement in QoL in all scales across all cycles (cemi: 55.9–86.8%; pbo: 55.5–88.2%). Median time to first deterioration was also similar between arms in all scales (cemi: 5.3–25.6 months; pbo: 8.3–22.2 months). Conclusions: QoL was maintained during treatment with adjuvant cemi, with no clinically meaningful worsening vs pbo. These PRO results complement the observed improvement in DFS and support the favorable risk profile of adjuvant cemi for pts with high-risk CSCC. Clinical trial information: NCT03969004 . QLQ-C30 scale Baselinemean (SD) Overall LS mean change from baseline (95% CI) Difference (95% CI) Cemi (n=209) Pbo(n=206) Cemi(n=209) Pbo(n=206) GHS/QoL 75.4 (17.5) 75.8 (17.4) –2.0 (–4.3, 0.4) –1.0 (–3.4, 1.4) –0.9 (–3.7, 1.8) PF 87.1 (16.0) 90.6 (13.9) –1.4 (–3.2, 0.5) –1.9 (–3.9, 0.0) 0.5 (–1.7, 2.7) RF 83.8 (24.8) 84.2 (20.8) –4.2 (–7.3, –1.2) –1.6 (–4.8, 1.5) –2.6 (–6.2, 0.9) EF 84.6 (18.7) 85.1 (16.7) 0.2 (–2.2, 2.7) –0.4 (–2.9, 2.1) 0.7 (–2.2, 3.5) FA 20.9 (19.9) 20.5 (20.1) 5.0 (2.2, 7.7) 4.2 (1.4, 7.0) 0.8 (–2.4, 4.0) PA 14.7 (21.2) 13.1 (20.4) 3.2 (–0.1, 6.5) 2.1 (–1.3, 5.6) 1.1 (–2.8, 5.0)

BACKGROUND:Patients who have cutaneous squamous-cell carcinoma with high-risk features are at risk for recurrence after definitive local therapy. The benefit of systemic adjuvant therapy options has not been well established in clinical trials. METHODS:In a phase 3, randomized trial, we enrolled patients with local or regional cutaneous squamous-cell carcinoma, after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features (extracapsular extension with largest node ≥20 mm in diameter or at least three involved nodes) or nonnodal features (in-transit metastases, T4 lesion [with bone invasion], perineural invasion, or locally recurrent tumor with ≥1 additional risk feature). Patients were assigned in a 1:1 ratio to receive adjuvant cemiplimab (350 mg) or placebo, administered intravenously every 3 weeks for 12 weeks, followed by a dose increase to 700 mg administered every 6 weeks for up to 36 weeks (≤48 weeks total). The primary end point was disease-free survival. Secondary end points included freedom from locoregional recurrence, freedom from distant recurrence, and safety. RESULTS:A total of 415 patients were assigned to cemiplimab (209) or placebo (206). The median follow-up was 24 months. Cemiplimab was superior to placebo with respect to disease-free survival (24 vs. 65 events; hazard ratio for disease recurrence or death, 0.32; 95% confidence interval [CI], 0.20 to 0.51; P<0.001). The estimated 24-month disease-free survival was 87.1% (95% CI, 80.3 to 91.6) with cemiplimab and 64.1% (95% CI, 55.9 to 71.1) with placebo. Cemiplimab led to lower risks of locoregional recurrence (9 events, vs. 40 with placebo; hazard ratio, 0.20; 95% CI, 0.09 to 0.40) and distant recurrence (10 vs. 26 events; hazard ratio, 0.35; 95% CI, 0.17 to 0.72). Adverse events of grade 3 or higher occurred in 23.9% of the patients who received cemiplimab and in 14.2% of those who received placebo; discontinuation due to adverse events occurred in 9.8% and 1.5%, respectively. CONCLUSIONS:Adjuvant cemiplimab therapy led to longer disease-free survival than placebo among patients at high risk for recurrence of cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; C-POST ClinicalTrials.gov number, NCT03969004.).

Generic health utility instruments lack the discriminative ability to differentiate among health states in patients after head and neck cancer treatment. To develop, validate, and valuate a head and neck cancer−specific health utility measure. This psychometric study comprised 2 phases to develop and validate a health utility instrument. The first phase, development and validation, occurred from January 2021 to August 2022. An expert panel selected disease-specific quality-of-life instruments as the basis for a new utility instrument. Two datasets (n = 458 and 493) were used to establish dimension structure through exploratory factor analysis, and to select items using Rasch and psychometric criteria and expert opinion. Discriminative validity of the new instrument was tested by comparing scores for different disease severities (patients with and without gastrostomy and tracheostomy tubes). The second phase, valuation, was conducted from January 2023 to January 2024 in a quaternary referral center with healthy participants. Participants completed time−trade-off exercises for 100 sampled health states and were randomized to discovery and validation sets (80:20). Using a repeated measures model, a scoring algorithm to predict utilities of health states within the instrument was created in the discovery set and tested in both sets. Data were analyzed from January 2022 to December 2023. Participants performed time−trade-off exercises for various states. Discriminative validity (first phase) and the mean absolute differences of predicted and observed utilities (second phase). The European Organization for Research and Treatment of Cancer’s Quality of Life Questionnaire−Core 30 and its Head and Neck module 43 were selected by the expert panel and used as the basis instruments. Exploratory factor analysis established 8 dimensions, with 1 item selected per dimension. Of the 488 respondents, 84 with gastrostomy and/or tracheostomy tubes reported lower scores for 7 of the 8 items. In the second phase, 2497 valuations were performed by 250 healthy participants (mean [SD] age, 42.4 [16.5] years; 166 [66%] females). The scoring algorithm produced mean absolute differences between predicted and observed utilities of 0.041 (95% CI, 0.034-0.047) and 0.082 (95% CI, 0.065-0.100) in the discovery and validation sets, respectively. This psychometric study developed a new head and neck cancer-specific utility measure, the HNC-8D (Head and Neck Cancer−8 Dimensions). The instrument demonstrated predictive accuracy for measuring health utility and can be used to differentiate health utility states following head and neck cancer treatment.

INTRODUCTION:The profile and outcomes of head and neck cancer throughout Australia has changed over the past decade. The aim of this study was to perform a population-based analysis of incidence, demographics, stage, treatments and outcomes of patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC), with a particular focus on HPV-associated disease. METHODS:This was a retrospective analysis of prospectively collected data within the Queensland Oncology Repository (QOR) and analysed by the Queensland Cancer Control Analysis Team. The cohort included patients diagnosed in Queensland between 1 January 2015 and 31 December 2019. Outcome measures included incidence of new OPSCC cases, age-standardised rates (ASR) (3-year average), demographics, p16 status, stage (8th Edition American Joint Commission on Cancer), treatments, and 2- and 5-year overall survival. RESULTS:There were 1527 newly diagnosed OPSCC, representing 96% (1527/1584) of all oropharyngeal cancers. It was the most common head and neck cancer diagnosed, with oral cavity cancer being the second most common (n = 1171). Seventy-seven percent were p16 positive (1170/1527), of which 87% (1019/1170) were male. The median age was 61 years and 49% (568/1170) presented with Stage I disease. The ASR was 6.3/100,000, representing a 144% incidence increase since 1982 (2.6/100,000). Radiotherapy was utilised in 91% of p16+ cases with 2- and 5- year overall survival of 89% and 79%, respectively. CONCLUSION:OPSCC is now the most common mucosal head and neck cancer diagnosed in Queensland, having surpassed oral cavity cancer. The majority are HPV-associated (p16+), presenting with early-stage disease with a favourable prognosis.

9514 Background: Neoadjuvant anti-Programmed Death therapy has shown a 64% complete or major pathological response rate in patients (pts) with resected stage II-IV(M0) cSCC. The De-Squamate study (NCT05025813) evaluated the feasibility of a risk adapted surgical de-escalation approach guided by clinical, radiological and pathological response in resectable cSCC pts of all sites receiving neoadjuvant pembrolizumab. Methods: This multi-centre, open-labelled, non-randomised, single-arm phase 2 study evaluated the response of neoadjuvant Pembrolizumab for 4 cycles administered IV 200mg Q3W in immunocompetent pts with Stage II-IV (M0) resectable cSCC. Pts underwent CT/MRI and 18F-FDG-PET imaging at baseline and following completion of neoadjuvant pembrolizumab. In those with a complete metabolic response, mapping biopsies of target site(s) were performed and if negative for residual SCC (clinical complete response [CCR]), surgery and post operative radiation therapy (PORT) were omitted. Patients with clinical or radiological residual disease/ positive mapping biopsy underwent surgical resection. PORT was de-escalated if there was a pathological complete response (PCR - no residual tumour cells) or major pathological response (MPR - less than or equal to 10% viable tumour cells). Pts proceeded to 13 cycles of maintenance Pembrolizumab. The primary endpoint was the combined rate of PCR, MPR and CCR following neoadjuvant Pembrolizumab and secondary endpoint includes treatment de-escalation and safety. Results: All 27 patients were enrolled and received a minimum of 2 cycles of neoadjuvant Pembrolizumab. The primary endpoint was observed in 17 patients (63%, 95% CI: 42-80), comprised of PCR (15%), MPR (0%) and CCR (48%). De-escalation of both surgery and PORT was achieved in 48% and a further 15% avoided PORT alone. With a minimum follow up of 6 months, no pts with PCR/MPR/CCR recurred. Investigator assessed treatment-related adverse events ≥ grade 3 was seen in 2 patients (7%). Conclusions: Pembrolizumab led to a high rate of PCR and CCR in resectable cSCC. The de-squamate study design effectively selected pts for surgical and PORT de-escalation and demonstrated a sustained response in this cohort. Clinical trial information: NCT05025813 .

BACKGROUND:There are no large studies reporting oncological or survival outcomes for patients diagnosed with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC) via the ophthalmic nerve (V1). Where orbital exenteration may be necessary for curative treatment, it is critical to have survival data with which the morbidity associated with surgical treatment can be justified. Furthermore, with the emerging treatment option of immunotherapy, current standard of care outcomes are needed to help guide future trial design and eventually changed management guidelines. OBJECTIVE:To determine the oncological and survival outcomes observed in patients with PNS of cSCC via V1. MATERIALS AND METHODS:Retrospective analysis of prospectively maintained cohort of patients with PNS of cSCC via V1 treated in a tertiary Australian head and neck oncology/skull base referral center. Consecutive sample of 53 patients managed between March 1, 1999 and April 30, 2020. Follow-up closure date was September 1, 2021. Curative-intent surgery, curative-intent radiotherapy, or palliative care was undertaken. Endpoints included five-year overall, disease-specific, and disease-free survival from the date of treatment. RESULTS:Five-year Kaplan-Meier overall survival was 61.9% (95% CI 46.2%-74.3%), with disease-specific survival of 74.6% (95% CI 58.8%-85.3%), and disease-free survival 62.1% (95% CI 46.5%-74.3%). Survival was superior in patients treated via surgery and adjuvant radiotherapy than in those receiving surgery alone or definitive radiotherapy. Survival was superior among patients with less advanced disease as assessed by the Williams zonal staging system; patients with Zone 1 disease had disease-specific survival of 94.1% at 5 years with 82.5% disease-free survival. DISCUSSION:Five-year oncological and survival outcomes in this cohort were favorable. Superior survival was observed in patients treated with curative-intent surgery and adjuvant radiotherapy. Less extensive disease as delineated by the Williams zonal staging system was associated with improved survival. CONCLUSION:Surgical resection with adjuvant radiotherapy confers favourable oncological and survival outcome in patients with V1 PNS, particularly with early disease limited to Zone 1.