Treatment results for nasopharyngeal carcinoma in the modern era: The Hong Kong experience

Purpose

To analyze the treatment results achievable for nasopharyngeal carcinoma in the modern era to identify the key failures for future improvement and to provide an updated baseline for future trials.

Methods and materials

The results of 2687 consecutive patients treated at all public oncology centers in Hong Kong during 1996–2000 were retrospectively analyzed. The stage distribution (by American Joint Committee on Cancer and International Union Against Cancer staging system, 1997) was 7% Stage I, 41% Stage II, 25% Stage III, and 28% Stage IVA–B. All patients were irradiated with 6-MV photons and the median total dose was 66 Gy. Only 23% of patients had additional treatment with chemotherapy.

Results

The 5-year local, nodal, and distant failure-free rates were 85%, 94%, and 81%, respectively; patients with local failure had significantly higher risk of nodal and distant failures. The 5-year progression-free, overall, and cancer-specific survival rates were 63%, 75%, and 80%, respectively. The presenting stage was the most important prognostic factor for all endpoints: with overall survival decreasing from 90% for Stage I to 58% for Stage IVA–B. The results achieved by the 2070 patients treated by radiotherapy alone were almost identical to that of the whole series, the distant failure-free rate among patients with locoregional control was 89% for Stage I–II and 75% for Stage III–IVB. The 860 patients (32%) staged with magnetic resonance imaging achieved significantly better results than those staged by computed tomography, the overall survival being 93% vs. 83% for Stages I–II, and 72% vs. 63% for Stages III–IVB (p = 0.001).

Conclusions

Treatment results for nasopharyngeal carcinoma have substantially improved in the modern era; future trials should be based on updated baseline results. Further reduction of distant failure is important for future breakthrough, particularly for patients with advanced disease.

Introduction

Review of the historical record shows that nasopharyngeal carcinoma was not fully recognized until the mid-19th century (1). Gloomy comments reflected the futility of treatment in the early 1900s: “Thoroughness was not attainable at the bottom of a deep pit, surgery merely added to anemia of cancerous cachexia” (2), and “the only effective remedies were opium, deception and lying” (3).

The development of radiation therapy (RT) revolutionized the management of nasopharyngeal carcinoma. At the beginning when radium insertion was the only mode available, the tumor almost invariably recurred despite good initial improvement (4). Even with introduction of kilo-voltage machines in the 1920s, patients seldom survived for 3 years (5). It was not until the advent of mega-voltage machines that long survival was first achieved: the review by Moss (6) in 1965 showing 25% of patients alive at 5 years marked the first major breakthrough, and established the role of RT as the primary modality of choice.

Progressive improvement of treatment results has since been reported both from endemic and nonendemic areas. The largest Asian series of 5037 patients treated in Queen Elizabeth Hospital (Hong Kong) during 1976–1985 (7) and the largest Western series of 378 patients treated in M. D. Anderson Cancer Center (United States) during 1954–1992 (8) both showed similar results with 5-year disease-specific survival (DSS) being 50%. This result can hence be taken as fairly representative of what conventional RT could achieve during that period.

Striving for continual improvement is obviously needed, particularly for patients with advanced disease. To prove the therapeutic benefit of a new treatment strategy by prospective randomized trial, one piece of crucial information for determining the accrual target is the primary endpoint achieved by “standard” treatment. With rapid technologic advances (in imaging methods, computerized planning systems, and RT facilities) and accumulation of radiobiological knowledge (on optimization of time, dose, and fractionation), better results might be achievable by aggressive RT in the modern era. Furthermore, with the major changes in the staging system by the American Joint Committee on Cancer (AJCC) (9) and the International Union Against Cancer (UICC) in 1997 (10), treatment results for corresponding stages will inevitably be different. Past data could no longer be relied upon as benchmark references.

The current study by the Hong Kong Nasopharyngeal Cancer Study Group aims to assess the effectiveness of contemporary treatment to identify the key failures for future improvement and to provide the baseline for future studies. The cohort of patients treated during the period January 1996 to June 2000 is selected for analysis because the staging and treatment strategies are more relevant to modern practice, and the follow-up period is reasonably adequate for assessment of tumor control. To provide the most representative data on treatment results achievable in Hong Kong, data from all public oncology centers are retrospectively analyzed.