Radiation therapy paradox: Better tumor response doesn't guarantee patient survival
A major analysis of esophageal cancer trials reveals that patients who achieve complete tumor elimination through chemotherapy alone live longer than those treated with combined chemoradiation—despite radiation producing higher tumor response rates. The finding challenges a decades-old assumption and could reshape treatment protocols for thousands of patients annually.
Originaltitel: Survival after pathological complete response following neoadjuvant chemotherapy <i>versus</i> chemoradiotherapy for oesophageal squamous cell carcinoma
BACKGROUND: Although several oesophageal squamous cell carcinoma (OSCC) studies have reported no definitive overall survival (OS) differences between neoadjuvant chemoradiotherapy (NACRT) and neoadjuvant chemotherapy (NAC), the higher pCR rate with NACRT has been viewed as a potential advantage. Beyond ongoing concerns about the validity of pCR as a surrogate endpoint, it remains uncertain whether survival differs between these modalities among patients with OSCC who achieve pCR. METHODS: An integrated analysis of individual patient data (IPD) from phase III trials evaluating perioperative therapies for resectable OSCC was conducted, emphasizing prognostic differences between NAC and NACRT, particularly among patients who achieved pCR. RESULTS: IPD from seven phase III RCTs across six countries included data for 1044 patients with OSCC (83.5% male; mean age of 62.3 years). Of these patients, 605 (58.0%) received NAC and 439 (42.0%) received NACRT, with R0 resection rates of 89.6% versus 84.7% and pCR rates of 6.9% versus 34.2% respectively. Among patients who achieved pCR (192 patients), 5-year OS was 97.5% in the NAC group and 70.4% in the NACRT group, while 5-year recurrence-free survival was 80.8% and 63.7% respectively. Multivariable analysis demonstrated a significant survival advantage for NAC among patients who achieved pCR. CONCLUSION: Among patients who achieved pCR, postoperative outcomes varied considerably by neoadjuvant treatment modality. The markedly favourable prognosis associated with pCR after NAC suggests that these patients may represent an optimal candidate cohort for future evaluation of surgery-avoidance and watch-and-wait strategies.