A change in the study evaluation paradigm reveals that larynx preservation compromises survival in T4 laryngeal cancer patients

BACKGROUND: Larynx preservation (LP) is recommended for up to low-volume T4 laryngeal cancer as an evidence-based treatment option that does not compromise survival. However, a reevaluation of the current literature raises questions regarding whether there is indeed reliable evidence to support larynx preservation for T4 tumor patients. METHODS: In an observational cohort study of 810 laryngeal cancer patients, we evaluated the outcomes of all T4 tumor patients treated with primary chemo-radiotherapy (CRT) or primary radiotherapy alone (RT) compared with upfront total laryngectomy followed by adjuvant (chemo)radiotherapy (TL + a[C]RT). Additionally, we reevaluated the studies that form the evidence base for the recommendation of LP for patients with up to T4 tumors (Pfister et al., J Clin Oncol 24:3693–704, 2006). RESULTS: The evaluation of all 288 stage III and IV patients together did not show a significant difference in overall survival (OS) between CRT-LP and TL + a(C)RT (hazard ratio (HR) 1.23; 95% confidence interval (CI): 0.82–1.86; p = 0.31) using a multivariate proportional hazard model. However, a subgroup analysis of T4 tumor patients alone (N = 107; 13.9%) revealed significantly worse OS after CRT compared with TL + a(C)RT (HR 2.0; 95% CI: 1.04–3.7; p = 0.0369). A reevaluation of the subgroup of T4 patients in the 5 LP studies that led to the ASCO clinical practice guidelines revealed that only 21–45 T4 patients had differential data on survival outcome. These data, however, showed a markedly worse outcome for T4 patients after LP. CONCLUSIONS: T4 laryngeal cancer patients who reject TL as a treatment option should be informed that their chance of organ preservation with primary conservative treatment is likely to result in a significantly worse outcome in terms of OS. Significant loss of survival in T4 patients after LP is also confirmed in recent literature.