De-Escalated Adjuvant Therapy After Transoral Robotic Surgery for Human Papillomavirus-Related Oropharyngeal Carcinoma: The Sinai Robotic Surgery (SIRS) Trial

Abstract

Background Treatment of human papillomavirus‐related oropharyngeal squamous cell carcinoma (HPVOPC) results in unprecedented high survival rates but possibly unnecessary toxicity. We hypothesized that upfront surgery and neck dissection followed by reduced‐dose adjuvant therapy for early and intermediate HPVOPC would ultimately result in equivalent progression‐free survival (PFS) and overall survival while reducing toxicity. Methods This study was a nonrandomized phase II trial for early‐stage HPVOPC treated with transoral robotic surgery (TORS) followed by reduced‐dose radiotherapy. Patients with previously untreated p16‐positive HPVOPC and <20 pack years’ smoking history were enrolled. After robotic surgery, patients were assigned to group 1 (no poor risk features; surveillance), group 2 (intermediate pathologic risk factors [perineural invasion, lymphovascular invasion]; 50‐Gy radiotherapy), or group 3 (poor prognostic pathologic factors [extranodal extension [ENE], more than three positive lymph nodes and positive margin]; concurrent 56‐Gy chemoradiotherapy with weekly cisplatin). Results Fifty‐four patients were evaluable; there were 25 in group 1, 15 in group 2, and 14 in group 3. Median follow‐up was 43.9 months (9.6–75.8). Disease‐specific survival was 98.1%, and PFS was 90.7%. PFS probability via Kaplan‐Meier was 91.3% for group 1, 86.7% for group 2, and 93.3% for group 3. There were five locoregional failures (LRFs), including one distant metastasis and one contralateral second primary. Average time to LRF was 18.9 months (9.6–59.0); four LRFs were successfully salvaged, and the patients remain disease free (11.0–42.7 months); one subject remains alive with disease. Conclusion The results indicate that upfront surgery with neck dissection with reduced‐dose radiation for T1–2, N1 stage (by the eighth edition American Joint Committee on Cancer staging manual) HPVOPC results in favorable survival with excellent function in this population. These results support radiation dose reduction after TORS as a de‐escalation strategy in HPVOPC. Implications for Practice Transoral robotic surgery can provide a safe platform for de‐escalation in carefully selected patients with early‐stage human papillomavirus‐related oropharyngeal cancer. In this clinical trial, disease‐specific survival was 100%, over 90% of the cohort had a reduction of therapy from standard of care with excellent functional results, and the five patients with observed locoregional failures were successfully salvaged.

Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis of Clinical Trial Demographics

“…This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRSIMA) guidelines ( Figure 1 ). A total of 32 studies with 2995 patients were included in the review [ 2 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ]. Table 1 shows the year, location, trial identifier (NCT number, RTO, etc.)…”

High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies

“…Recent evidence showed that treatment de-intensification leads to worse outcomes: current knowledges are insufficient to recommend changes in treatments based on HPV status [ 13 , 108 ]. However, it has been recently shown that, in selected patients, transoral robotic surgery (TORS) with de-escalating adjuvant radiotherapy is effective and less toxic, thus suggesting that further investigations could lay the basis to enroll specific patients in which this strategy could turn out as promising [ 109 ].…”

Human Papillomavirus-Related Non-Metastatic Oropharyngeal Carcinoma: Current Local Treatment Options and Future Perspectives

“…Active smokers may especially benefit from adjuvant RT following TORS. The DSS observed in 15 intermediate-risk HPV+ OPSCC patients in a study published by Miles et al was 86.7% [ 51 ].…”