Postop adjuvant treatment yields survival benefit for stage IIB-III oesophageal SCC

The addition of postoperative radiotherapy (PORT) or postoperative concurrent chemoradiotherapy (POCRT) to surgery led to significant improvements in disease-free survival (DFS) and overall survival (OS) in individuals with pathological stage IIB-III oesophageal squamous cell carcinoma (SCC) compared with surgery alone, a prospective phase III study from China suggests.

“[Our] study is the first randomized controlled trial to explore the effect of postoperative adjuvant therapy for [this patient subgroup]. The findings suggest that postoperative treatment … may significantly improve survival in these patients,” said the researchers.

“[E]specially superior efficacy was seen with POCRT … PORT with a reduced radiation field combined with chemotherapy (CT) appears to be an effective and safe treatment, with the potential for being accepted as standard treatment option for [these patients] after radical surgery,” they continued.

A total of 172 participants (median age 59 years, 90 percent male) were randomized to receive surgery either alone (SA; n=54) or with PORT (54 Gy in 27 fractions; n=54) or POCRT (50.4 Gy in 28 fractions, plus concurrent CT* every 28 days; n=64). [Oncologist 2021;26:e2151-e2160]

Compared with SA, PORT/POCRT had significantly better 3-year DFS (median 48.3 vs 17.5 months; hazard ratio [HR], 0.58; p=0.020) and OS (median not reached vs 31.4 months; HR, 0.57; p=0.025).

The 3-year DFS rates for the respective POCRT, PORT, and SA arms were 57, 50, and 37 percent. The corresponding 3-year OS rates were 66, 61, and 48 percent, respectively. The differences between POCRT and SA were significant for both DFS (p=0.015) and OS (p=0.016).

Compared with PORT, POCRT was associated with significantly higher rates of grade 3/4 leukopenia (45 percent vs 4 percent) and neutropenia (33 percent vs 0 percent; p<0.001 for both). Conversely, the rates of nonhaematologic toxicities between the PORT and POCRT arms were similar, the most common being grade 1/2 radiation oesophagitis (85 percent vs 81 percent) and radiodermatitis (76 percent vs 77 percent). The rate of hematogenous metastases was slightly lower with POCRT than with PORT (20 percent vs 26 percent). One patient receiving POCRT died of radiation pneumonitis.

“[T]he relatively high rate of adverse effects in patients treated with POCRT did not result in increased mortality, which was actually extremely low … Thus, postoperative treatment with the regimen used in our study appears to be reasonable and well-tolerated and deserves to be adopted in clinical practice,” said the researchers.

New techniques = improvement?

“[Our findings show that] a postoperative CRT regimen that used a combination of small radiation target volume plus paclitaxel and cisplatin or nedaplatin proved effective and safe,” said the researchers. “Patients treated with PORT and POCRT had similar in-field and out-of-field recurrence, and the latter had lower incidence of hematogenous metastasis. Importantly, the postoperative treatment did not increase risk of mortality.”

The continued improvements in surgical techniques and introduction of new radiation techniques may have factored in the improved survival benefit achieved with PORT/POCRT, the researchers noted. For instance, the use of video-assisted thoracoscopic surgery for oesophagectomy facilitated a more extensive resection of mediastinal lymph nodes.

Moreover, the use of IMRT or VMAT** as adjuvant treatment may have improved survival by protecting normal tissues while delivering the appropriate dose. “Thus, the significantly improved OS and DFS … can be attributed to the survival benefit conferred by postoperative adjuvant treatment rather than to the poor survival in the SA arm,” the researchers said.

However, the findings appear to deviate from previous reports either favouring POCRT over PORT or showing no difference between the two regimens. [Int J Radiat Oncol Biol Phys 2013;86:671-677; Cancer Manag Res 2020;12:1631-1639; Thorac Cancer 2020;11:631-639] As such, the researchers called for further studies with larger populations and longer follow-up durations to validate the results.