Impact of Postoperative Radiotherapy Versus PD-1 Inhibitor Maintenance on Survival in Resectable Locally Advanced Oral and Oropharyngeal Squamous Cell Carcinoma

Impact of Postoperative Radiotherapy Versus PD-1 Inhibitor Maintenance on Survival in Patients With Resectable Locally Advanced Oral and Oropharyngeal Squamous Cell Carcinoma Treated With Neoadjuvant Immunochemotherapy and Radical Surgery: A Single-Center Ambispective Cohort Study

Neoadjuvant immunochemotherapy (NAIC) has demonstrated promising pathological and survival outcomes in patients with resectable locally advanced oral and oropharyngeal squamous cell carcinoma (LA-OSCC/OPSCC). However, the optimal postoperative management strategy following NAIC and radical surgery remains undefined, particularly regarding the necessity of postoperative radiotherapy and the potential role of PD-1 inhibitor maintenance therapy.

This single-center, ambispective cohort study aims to compare event-free survival, pathological response, survival outcomes, failure patterns, treatment-related toxicities, and functional outcomes among three postoperative strategies: postoperative radiotherapy, postoperative PD-1 inhibitor maintenance, and observation alone. The study seeks to provide real-world evidence to support risk-adapted, individualized postoperative decision-making after NAIC

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Oropharyngeal Squamous Cell Carcinoma; Locally Advanced Oral Squamous Cell Carcinoma
• Intervention / Treatment: Other: Observation; Radiation: Postoperative Radiotherapy; Drug: PD-1 Inhibitor Maintenance Therapy

Detailed Description

Patients with resectable LA-OSCC/OPSCC who received two cycles of neoadjuvant immunochemotherapy consisting of tislelizumab combined with paclitaxel and platinum chemotherapy, followed by R0 radical resection, were included. Based on multidisciplinary clinical decisions, pathological risk stratification, and patient preference, participants were managed postoperatively with one of three strategies:

1. Postoperative radiotherapy
2. Postoperative PD-1 inhibitor maintenance therapy
3. Observation without adjuvant therapy

The study incorporates both retrospective and prospective cohorts using identical eligibility criteria, treatment regimens, follow-up schedules, and outcome assessments to ensure data homogeneity. Survival outcomes, pathological response, treatment-related adverse events, and functional outcomes are systematically evaluated.

• Study Type: Observational
• Enrollment (Estimated): 85

Contacts and Locations

• Study Contact: Name: Xiaozhi LV; Phone Number: 02062783160; Email: lxzsurgeon@126.com

Study Locations

• China
  • Guangzhou, China
    • Department of Stomatology, Zhujiang Hospital, Southern Medical University, Haizhu District, Guangzhou, Guangzhou, Guangdong 510282
    • Contact: Xiaozhi LV; Phone Number: 02062782092; Email: lxzsurgeon@126.com
    • Contact: Email: lxzsurgeon@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (18-80 years) with histologically confirmed, treatment-naïve, locally advanced oral or oropharyngeal squamous cell carcinoma who were surgically resectable and had ECOG performance status 0-1. All participants received two cycles of neoadjuvant immunochemotherapy (tislelizumab plus paclitaxel and platinum) followed by R0 radical surgery and were managed postoperatively with radiotherapy, PD-1 inhibitor maintenance, or observation. Patients with prior head and neck radiotherapy, active autoimmune disease, uncontrolled severe comorbidities, pregnancy/lactation, or incomplete data were excluded.

Description

Inclusion Criteria:

1. Age 18-80 years, any gender.
2. Expected survival ≥ 6 months.
3. Adequate major organ function; ECOG performance status 0-1.
4. Treatment-naïve patients diagnosed with locally advanced oral squamous cell carcinoma (LA-OSCC) or locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC), in accordance with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system (2017) and the 2020 Chinese Stomatological Association (CSA) guidelines for pathological diagnosis of oral and oropharyngeal cancers, with clinical stages: cT3N0M0, cT1-3N1M0, cT4aN0-2M0, cT1-4aN3M0, or cT4bN0-3M0.
5. No evidence of distant metastasis based on auxiliary examinations.
6. No prior antitumor treatment, including surgery, radiotherapy, chemotherapy, immunotherapy, targeted therapy, or other antitumor therapies.
7. Received 2 cycles of neoadjuvant chemoimmunotherapy (toripalimab + TP regimen) and underwent R0 resection.
8. Women of childbearing potential must agree to use effective contraception during treatment and for 3 months after.
9. Signed informed consent (if the participant lacks capacity, by a legally authorized representative), voluntarily participates in the study, and demonstrates good compliance.

Exclusion Criteria:

1. History of radiotherapy to the head and neck region.
2. Severe bone marrow suppression, hepatic or renal failure, or uncontrolled severe infections, cardiovascular diseases, or other conditions that may preclude tolerance of treatment.
3. Active autoimmune diseases, history of organ transplantation requiring long-term immunosuppressive therapy, or severe immunodeficiency that may result in serious immune-related adverse events.
4. Active infections requiring systemic therapy.
5. Cardiovascular/cerebrovascular events within 6 months prior to study treatment, including myocardial infarction, severe/unstable angina, coronary or peripheral artery bypass surgery, symptomatic heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
6. Bleeding tendency/disorders: clinically significant bleeding or clear bleeding tendency within the past 28 days, including but not limited to gastrointestinal bleeding, epistaxis (excluding mild nosebleeds or blood-streaked sputum), or persistent bleeding/clotting disorders.
7. History of substance abuse, alcoholism, or drug abuse.
8. Pregnant or breastfeeding women.
9. Participation in other interventional clinical trials simultaneously.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No Adjuvant Therapy Group; Patients received neoadjuvant immunochemotherapy followed by R0 radical surgery, with no postoperative adjuvant treatment and routine follow-up only.	Other: Observation; Participants received neoadjuvant immunochemotherapy followed by R0 radical surgical resection. No postoperative adjuvant therapy was administered. Patients were managed with routine clinical follow-up, including scheduled physical examinations, imaging assessments, and functional evaluations according to institutional practice.; Other Names: Active surveillance; Observation only; No postoperative adjuvant therapy
Postoperative Radiotherapy Group; Patients received neoadjuvant immunochemotherapy followed by R0 radical surgery and postoperative radiotherapy according to multidisciplinary team decision.	Radiation: Postoperative Radiotherapy; Participants received neoadjuvant immunochemotherapy followed by R0 radical surgical resection and postoperative radiotherapy. Radiotherapy was delivered to the primary tumor bed and regional lymphatic drainage areas according to multidisciplinary team recommendations and institutional guidelines.; Other Names: Adjuvant radiotherapy; Postoperative radiation therapy (PORT); Radiation therapy after surgery
Postoperative Immunotherapy Maintenance Group; Patients received neoadjuvant immunochemotherapy followed by R0 radical surgery and postoperative PD-1 inhibitor maintenance therapy.	Drug: PD-1 Inhibitor Maintenance Therapy; Participants received neoadjuvant immunochemotherapy followed by R0 radical surgical resection and postoperative immunotherapy maintenance with a PD-1 inhibitor. Immunotherapy was administered at standard dosing intervals according to institutional protocols until disease progression, unacceptable toxicity, or completion of the planned treatment course.; Other Names: Programmed cell death protein 1 inhibitor; Immune checkpoint inhibitor maintenance; PD-1 antibody maintenance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-Year Event-Free Survival (EFS)	Time from the date of radical surgery to the first occurrence of disease recurrence (local, regional, or distant), disease progression, death from any cause, or last follow-up, whichever occurs first.	1-Year
Pathological Complete Response (pCR) Rate	Pathological complete response (pCR) is defined as the absence of residual viable tumor cells in both the primary tumor site and all resected lymph nodes, as assessed by postoperative histopathological examination.	At the time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-Year Overall Survival (OS)	Time from the date of surgery to death from any cause or last follow-up.	1-Year
Major Pathological Response (MPR) Rate	Major pathological response is defined as ≤10% residual viable tumor cells in the surgical specimen, as determined by histopathological evaluation	At the time of surgery
Failure Patterns	Distribution of recurrence events categorized as local, regional, or distant.	1-Year
Incidence of Grade ≥3 Radiotherapy-Related Toxicities (RTOG/EORTC)	The incidence of grade 3 or higher radiotherapy-related toxicities, assessed according to the Radiation Therapy Oncology Group / European Organisation for Research and Treatment of Cancer (RTOG/EORTC) toxicity criteria. Toxicity grades range from Grade 0 (no toxicity) to Grade 5 (death related to toxicity), with higher grades indicating more severe toxicity.	1-Year
Incidence of Grade ≥3 Immunotherapy-Related Adverse Events (NCI-CTCAE v6.0)	The incidence of grade 3 or higher immunotherapy-related adverse events, assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 6.0. Adverse event grades range from Grade 1 (mild) to Grade 5 (death related to adverse events), with higher grades indicating more severe toxicity.	1-Year
Swallowing Function	Swallowing function was assessed based on clinically documented swallowing evaluations during follow-up visits, including physician-reported functional assessments. Functional status was categorized according to institutional clinical practice, with higher functional levels indicating better swallowing ability.	1-Year
Nutritional Status Assessed by NRS-2002 Score	Nutritional status was assessed using the Nutritional Risk Screening 2002 (NRS-2002) score. The NRS-2002 score ranges from 0 to 7, with higher scores indicating greater nutritional risk.	1-Year
Quality of Life (Clinically Documented Functional Assessment)	Quality of life was assessed based on clinically documented functional assessments recorded during routine follow-up visits. Evaluations focused on patient-reported symptoms and functional status related to daily activities.	1-Year

Collaborators and Investigators

• Sponsor: Zhujiang Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: January 25, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 9, 2026

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 3, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: PD-1 inhibitor; oral cancer; oropharyngeal cancer; real-world study; Neoadjuvant immunochemotherapy; event-free survival; postoperative radiotherapy; pathological response
• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Mouth Neoplasms; Oropharyngeal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Health Services Administration; Investigative Techniques; Methods; Therapeutics; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Quality of Health Care; Radiotherapy; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Combined Modality Therapy; Immune Checkpoint Inhibitors; Observation; Watchful Waiting; Radiotherapy, Adjuvant
• Other Study ID Numbers: 2025-KY-505

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No