The Truths and Myths of Radiotherapy for Verrucous Carcinoma of Larynx

Abstract

Verrucous carcinoma (VC) of the larynx is infrequently managed by primary radiotherapy (RT) due to the “fear” of anaplastic transformation; additional reservations have included an increased incidence of nodal metastases and poor local control after RT. To address these concerns, we report our extended experience of moderate dose RT for this disease. All cases of laryngeal VC registered in our institutional-based Cancer Registry between 1961 and 2004 were reviewed retrospectively. Inclusion criteria comprised a convincing clinico-pathologic description; a diagnosis of VC established prior to treatment (thus VC assigned at recurrence was not eligible); treatment at our institution; and primary RT. All cases were restaged according to the 6th edition UICC TNM staging criteria. Outcome variables analyzed were locoregional control (LC), overall survival (OS) and cause-specific survival (CSS), outcome of salvage treatment, and the occurrence of either regional lymph node metastasis or anaplastic transformation. LC, OS and CSS were calculated with Kaplan-Meier method. Sixty-two eligible cases (54 males and 8 females) were identified. Minimum follow-up was 2 years (median: 11 years). Median age was 61 years (range: 34–83 years). The stage distribution was T1 = 19; T2 = 36; T3 = 6; T4 = 1; N0 = 60; N1 = 2 (T2N1 & T3N1). Most were Stage I/II (54/62 or 87%). Disease subsites were: glottis = 51; supraglottis = 10; subglottis = 1. Vocal cord movement was impaired in 17 and fixed in 6 cases. RT included 50 Gy/20f/4 weeks (n = 47), 55–60 Gy/25f in 5 weeks (n = 10) and others (n = 5). Local failure was classified in 20 patients following RT and 1 additional patient had regional lymph node failure. No case had anaplastic transformation. Median time to recurrence was 1.79 years (range 0.46–5.68 years). Salvage surgery was undertaken in 18 of 21 (86%) cases with loco-regional failure (9 total laryngectomy; 5 partial laryngectomy; 3 laser surgery; 1 neck dissection). Salvage surgery achieved disease control in 17/18 (94%) cases; the remaining case died of complications of salvage surgery. Three recurrent cases did not undergo salvage surgery because of medical co-morbidity (n = 1), death from disease prior to surgery (n = 1) or non-progression over 15 years of apparently proven disease in the absence of any salvage treatment (n = 1). No distal failure was observed. Secondary cancers were identified after RT in 4 cases including prostate cancer (2), lung cancer (1), and laryngeal cancer manifesting 11 years later in the final case. Of the 39 deceased patients, only 3 died of VC including one from complications related to salvage surgery. LC, OS and CSS at 5-years were 66% (95% CI: 52–77), 87% (75–93) and 97% (87–99) respectively. The local control of laryngeal verrucous carcinoma with moderate dose radiotherapy is somewhat inferior to ordinary squamous cell carcinoma. However it is regularly salvaged successfully following locoregional failure. Neither anaplastic transformation nor unusual nodal metastasis was observed in this series. The opportunity for laryngeal preservation in two-thirds of cases continues to make primary radiotherapy for verrucous carcinoma an attractive approach. Whether intensified treatment approaches, such as higher doses or concurrent chemo-radiotherapy, may improve local control remains unknown.