Incidence and Predictors of Early Recurrence in Hypopharyngeal Carcinoma Treated with Radical Intent: A Retrospective Analysis from Tertiary Care Centre
Dr Mohanapriya A *1, Dr Pusuluri Veera Venkata Sunil 1
*Correspondence to: Dr Mohanapriya A, Department of Radiation Oncology, GSL Medical College and General Hospital, Rajahmundry, India.
Copyright
© 2026 Dr Mohanapriya A is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 19 August 2026
Published: 01 September 2026
DOI: https://doi.org/10.5281/zenodo.22241821
Abstract
Background: Hypopharyngeal carcinoma (HPC) is an aggressive head and neck malignancy that frequently presents with advanced disease and carries poor survival outcomes. Early residual or recurrent disease remains a major therapeutic challenge. This study evaluated the incidence, patterns, and clinicopathological factors associated with early residual/recurrent disease in patients with HPC treated with curative intent.
Methods: This retrospective observational study included patients with biopsy-proven HPC treated with radical radiotherapy, with or without concurrent chemotherapy, between January 2022 and December 2024 at a tertiary care centre in India. Patients with metastatic disease at presentation, incomplete treatment, palliative treatment, or inadequate follow-up were excluded. Demographic, clinical, pathological, staging, treatment, response, and follow-up data were collected. Residual disease was defined as persistent disease detected within 6 months of treatment completion, while early recurrence was defined as local, regional, or distant recurrence within 12 months. Disease-free survival (DFS) and overall survival (OS) were assessed.
Results: Of 120 patients treated during the study period, 104 were eligible for analysis. The mean age was 54 years, and 59.8% were women. Most patients presented with advanced disease, with 92.5% having stage III or IV disease. Squamous cell carcinoma constituted 98.3% of cases. All patients received radical radiotherapy, predominantly 66 Gy in 33 fractions, and 97% received concurrent chemotherapy. Neoadjuvant chemotherapy was administered in 12.5% of patients.Residual disease was observed in 25 patients (24%), with the majority detected within 3 months of treatment completion. Local, nodal, and distant residual disease were observed in 12, 6, and 3 patients, respectively. Larger primary tumors and nodal involvement, particularly extranodal extension, were more frequent among patients with residual disease. The mean DFS and OS for the entire cohort were 9.25 and 13.85 months, respectively. Patients with residual disease had markedly poorer DFS (3.3 months) compared with those without residual disease (11.6 months).
Conclusion: Hypopharyngeal carcinoma demonstrates poor outcomes, largely related to advanced-stage presentation, bulky primary disease, and nodal involvement. Early residual disease is common and is associated with substantially inferior survival. Identification of high-risk clinicopathological features may facilitate closer surveillance and consideration of individualized treatment strategies. Prospective studies incorporating advanced imaging and radiomic biomarkers are warranted to improve risk stratification and outcomes in HPC.
Introduction
Hypopharyngeal carcinoma (HPC), a subset of head and neck carcinomas (HNC), remains relatively rare but notoriously aggressive. According to GLOBOCAN 2022, there were 86,257 new cases and 40,902 deaths globally, with HPC ranking 24th in incidence worldwide [1]. In India, HNC accounts for approximately 30% of all malignancies, and HPC is the third most common HNC subtype. GLOBOCAN 2022 estimates 30,510 new HPC cases and 11,618 deaths in India, ranking 15th in incidence and 20th in mortality globally [2].
Anatomically, most HPC tumors arise from the pyriform sinus, followed by the posterior pharyngeal wall and post-cricoid region. The post-cricoid subset is relatively more common in the Indian population, likely due to the prevalent use of smokeless tobacco [3]. The hypopharynx has a rich submucosal lymphatic network and close proximity to the larynx, cervical esophagus, and prevertebral fascia, which contributes to early submucosal spread and nodal metastasis. Anatomical factors such as involvement of multiple subsites, esophageal extension, cartilage invasion, and prevertebral fascia infiltration have been strongly associated with poor prognosis and treatment outcomes [4].
Despite its relatively low incidence, HPC carries a worse prognosis compared to other head and neck sub-sites. This is largely attributed to higher rates of advanced-stage disease at presentation, early lymph node involvement, and a propensity for occult metastatic spread [5]. The five-year survival remains dismal—less than 40% in patients with advanced disease [6].
The management of HPC involves multimodal treatment strategies, including surgery followed by adjuvant radiotherapy or concurrent chemoradiotherapy (CCRT), with the adoption of modern techniques such as Intensity-Modulated Radiotherapy (IMRT) aimed at organ preservation and improved local control [7,8].
Early recurrence—defined as local, regional, or distant relapse within 6–12 months of treatment—is an important clinical concern. It significantly worsens overall survival and often reflects aggressive tumor biology and challenges in achieving durable locoregional control [9]. Identifying clinicopathological predictors of early recurrence is therefore crucial to optimize surveillance, tailor therapeutic strategies, and improve outcomes.
This study aims to evaluate the incidence, patterns of recurrence (i.e., local, regional, or distant), and clinicopathological predictors of early recurrence in patients with HPC treated with curative intent at tertiary care centers in India.
Methods and Materials
This is a retrospective observational study conducted at our institution, a tertiary care centre in India. The study includes patients with biopsy proven carcinoma of hypopharynx treated with curative intent between January 2022 and December 2024.
Inclusion criteria: Histologically confirmed carcinoma of the hypopharynx, patients treated with radical radiotherapy (RT) and patients with clinical and radiological follow-up data for at least 12 months. Metastatic disease at presentation, incomplete treatment or lost to follow up before 3 months post treatment and patients treated with palliative intent were excluded from the study.
Treatment strategies included definitive chemoradiation, or radiation alone, as per institutional protocols and patient suitability.
Data collection
Patient’s clinical data and treatment details were collected from hospital medical records and radiation registry. Demographics data- age, gender, comorbidities, tobacco/alcohol use, Tumour characteristic- subsites, TNM stage, presence of multiple subsites involvement, Treatment details- radiotherapy dose & fractionation and techniques, concurrent chemotherapy, response to treatment, follow -up data were collected.
Follow-up Protocol and Outcome assessment
All patients were advised for follow-up every 2-3 months for first year post treatment, with clinical examination, pharyngolaryngoscopy and imaging (CT/MRI/PET-CT) as indicated and patients affordability, followed by every 6 months till 5 years , annually thereafter.
The primary objective was to assess the incidence and predictors of early recurrence, defined as local, regional, or distant relapse within 12 months of treatment completion. Residual disease was defined as persistent tumor detected within 6 months post-treatment, confirmed by clinical evaluation and imaging (CT or MRI).
Survival outcomes, including disease-free survival (DFS) and overall survival (OS), were calculated from the date of treatment completion to the date of recurrence, death, or last follow-up. Patients lost to follow-up were censored at the last contact date. Descriptive and comparative analyses were performed to evaluate clinicopathological correlates with residual and early recurrent disease.
Results
Out of 120 patients with histologically confirmed hypopharyngeal carcinoma treated between January 2022 and December 2024, a total of 104 patients were eligible for final analysis. Seven patients defaulted during treatment, and nine patients expired before treatment completion. The mean age at presentation was 54 years (range: 32–81 years), with the majority falling in the 41–50 years age group (29.5%), followed by the 51–60 years group (26.2%). A female preponderance was noted, with 59.8% of the cohort being women.
The most common presenting symptoms were dysphagia and odynophagia, followed by neck swelling, referred otalgia, and hoarseness of voice. A significant proportion of patients presented with advanced disease, with Stage IVA in 32.5% and Stage IVB in 14.2%, accounting for a total of 46.7%. Stage III disease was observed in 45.8%. Squamous cell carcinoma was the predominant histology, observed in 98.3% of patients, with moderately differentiated SCC being the most common subtype (50.4%).
All patients received radical radiotherapy, with the majority treated to a dose of 66 Gy in 33 fractions, while others received 70 Gy in 35 fractions. Concurrent chemotherapy was administered in 97% of cases, with the most common regimen being 3-weekly cisplatin (45.5%), followed by weekly carboplatin (30.7%). Additionally, 13 patients (12.5%) received neoadjuvant chemotherapy, most commonly the DCF regimen (Docetaxel, Carboplatin, 5-Fluorouracil).
At the time of last follow-up, 59 patients (56.7%) had expired. Residual disease was observed in 25 patients (24%), with 16 of them (64%) detected within 3 months of treatment completion and 8 patients (32%) within 6 months. Of those with residual disease, 12 patients had local residual, 6 had nodal residual, and 3 patients developed distant metastases, with the lung being the most common site.
Most patients with locoregional residual disease were advised salvage surgery, but due to patient unwillingness, 12 patients received palliative chemotherapy, most commonly the Paclitaxel-Carboplatin regimen. Only 2 patients underwent total laryngectomy.
Analysis of the residual disease group revealed that most patients presented with locally advanced stages (III, IVA, IVB), and 15 patients (58%) had nodal involvement, including 2 with extranodal extension. The mean tumor length in the residual group was 5.25 cm, compared to 4.75 cm in patients without residual disease.
The overall mean DFS and OS were 9.25 months and 13.85 months, respectively. For patients with residual disease, the mean DFS was 3.3 months and OS was 12.8 months, while for those without residual disease, the mean DFS was 11.6 months and OS was 14.4 months.
Discussion
Hypopharyngeal carcinoma is often diagnosed at an advanced stage due to its deep anatomical location and non-specific early symptoms, contributing to poor prognosis and high recurrence rates. In our study, the majority of patients (92.5%) presented with Stage III or IV disease, aligning with findings from Chen et al., who reported similarly high rates of advanced-stage presentation at diagnosis [10].
The observed mean overall survival (OS) of 13.85 months and disease-free survival (DFS) of 9.25 months in our cohort is consistent with real-world data published by Garneau JC et al., where lesser OS was noted for patients with locally advanced disease despite multimodal therapy [11]. Patients with residual disease in our study had particularly poor DFS (3.3 months), further emphasizing the prognostic impact of incomplete response to treatment.
Residual disease was more likely in patients presenting with larger tumors (mean size 5.25 cm vs. 4.75 cm) and nodal involvement—particularly those with extranodal extension. This reinforces the findings of Ho et al., who identified nodal burden and extranodal spread as significant predictors of poor survival in head and neck cancers, especially hypopharyngeal and laryngeal sites [12,13].
Our study showed that 23% of patients developed early residual disease, most within 6 months of treatment completion. Rie Nakahara et al. similarly reported early recurrence (within 6 months) in approximately 20% of patients, correlating with advanced T and N stages and poor response to chemoradiotherapy [14]. Additionally, the strong association between large primary tumor volume and early recurrence in our population mirrors the findings of Chen SW et al., who demonstrated tumor volume as a significant prognostic factor in hypopharyngeal cancer [15].
While radical radiotherapy with concurrent chemotherapy remains the standard of care, our study highlights that nearly one-third of patients with residual or recurrent disease were managed palliatively, often due to inoperability or patient unwillingness for surgery. Only 2 patients underwent salvage total laryngectomy, a procedure that has been shown to improve outcomes in select patients with residual loco-regional disease [16].
The predominance of moderately differentiated squamous cell carcinoma (50.4%) in our cohort is consistent with global histopathological trends [6], further supporting that tumor biology may not significantly vary across populations, but outcomes are influenced more by stage, nodal burden, and treatment completion.
Recent advances in radiomics offer promising tools to improve outcome prediction in hypopharyngeal carcinoma. CT-based radiomic features have been correlated with PD-L1 expression and immune response in head and neck cancers, potentially enabling non-invasive prediction of immunotherapy response [17]. Although still under evaluation in HPC, integrating radiomics into clinical practice may help personalize surveillance and treatment, especially in recurrent or metastatic settings.
Induction chemotherapy (NACT) has been explored as a means to downstage bulky disease, improve organ preservation, and potentially reduce early recurrence in locally advanced hypopharyngeal carcinoma. In our cohort, 12.5% of patients received NACT, predominantly the DCF regimen (Docetaxel, Cisplatin/Carboplatin, 5-FU). However, despite this, a considerable proportion still developed residual or recurrent disease, emphasizing the aggressive nature of the tumor.
Several studies have evaluated the impact of NACT in hypopharyngeal cancers. More recent trials such as TAX 324 also suggested improved disease control and laryngeal preservation with TPF (Docetaxel, Cisplatin, 5-FU) compared to PF regimen [18]. However, the impact on early recurrence remains modest, particularly in patients with high-risk features like large tumor volume, nodal metastasis, and poor response to chemotherapy.
Conclusion
Hypopharyngeal carcinoma has poor outcomes due to late presentation and early recurrence. In our cohort, advanced stage, bulky tumors, and nodal involvement were linked to early residual or recurrent disease. While radical chemoradiotherapy remains standard, induction chemotherapy showed variable benefit, underscoring the need for better selection criteria. Future integration of radiomics and personalized approaches may help improve outcomes in this high-risk group.
Limitations
This was a retrospective, single-center study with a limited sample size and follow-up duration. Treatment compliance varied, and a few patients were lost to follow-up or defaulted during therapy, which may affect the generalizability of the findings.
References