Ancona E, Ruol A, Castoro C, Chiarion-Sileni V, Merigliano S, Santi S, Bonavina L, Peracchia A
Second Department of General Surgery, University of Padua Medical School, Padova, Italy.
Ann Surg. 1997 Dec;226(6):714-23; discussion 723-4. doi: 10.1097/00000658-199712000-00008.
The objective of this prospective, nonrandomized study was to evaluate the immediate and long-term results of first-line chemotherapy and possible surgery in locally advanced, presumably T4 squamous cell esophageal cancer.
Locally advanced esophageal cancer is rarely operable and has a dismal prognosis. For this reason, neoadjuvant cytoreductive treatments are more and more frequently used with the aim of downstaging the tumor, increasing the resection rate, and possibly improving survival.
From January 1983 to December 1991, 163 consecutive patients with a presumedly T4 squamous cell carcinoma of the thoracic esophagus (group A) received on average 2.5 cycles (range, 1-6) of first-line chemotherapy with cisplatin (100 mg/m2 on day 1) and 5-fluorouracil (1000 mg/m2 per day, in continuous infusion from day 1 through day 5). Chemotherapy was followed by surgery when adequate downstaging of the tumor was obtained.
Chemotherapy toxicity was WHO grade 0 to 2 in 80% of cases, but 3 toxic deaths (1.9%) occurred. Restaging suggested a downstaging of the tumor in 101 of 163 patients (62%), but only 85 patients (52%) underwent resection surgery; it was complete or R0 in 52 (32%) and incomplete or R1-2 in 33. Overall postoperative mortality was 11.7% (10 of 85), morbidity 41% (35 of 85). Complete pathologic response was documented in 6 patients, and significant downstaging to pStage I, IIA, or IIB occurred in 25 more patients. The overall 5-year survival was 11 % (median, 11 months). After resection surgery, the 5-year survival was 20% (median, 16 months); none of the nonresponders survived 4 years after palliative treatments without resection (median survival, 5 months). The 5-year survival rate of the 52 patients undergoing an R0 resection was 29% (median, 23 months). Stratifying patients according to the R, pT, pN, and pStage classifications, the survival curves were comparable to the corresponding data obtained in the 587 group B patients with "potentially resectable" esophageal cancer who underwent surgery alone during the same period. Furthermore, the results were improved in comparison with 136 previous or subsequent patients with a locally advanced tumor who did not undergo neoadjuvant treatments (group C). In these patients, the R0 resection rate was 7%, and the overall 5-year survival was 3% (median, 5 months).
Although nonrandomized, these results suggest that in locally advanced esophageal carcinoma, first-line chemotherapy increases the resection rate and improves the overall long-term survival. In responding patients who undergo R0 resection surgery, the prognosis depends on the final pathologic stage and not on the initial pretreatment stage.
本前瞻性、非随机研究的目的是评估一线化疗及可能的手术治疗对局部晚期、推测为T4期的食管鳞状细胞癌的近期和远期疗效。
局部晚期食管癌很少能手术切除,预后很差。因此,新辅助细胞减灭治疗越来越多地被用于使肿瘤降期、提高切除率并可能改善生存率。
1983年1月至1991年12月,163例连续的推测为胸段食管T4期鳞状细胞癌患者(A组)平均接受了2.5个周期(范围1 - 6个周期)的一线化疗,化疗方案为顺铂(第1天100mg/m²)和5-氟尿嘧啶(每天1000mg/m²,从第1天持续输注至第5天)。当肿瘤获得充分降期后进行手术。
80%的病例化疗毒性为WHO 0至2级,但发生了3例毒性死亡(1.9%)。重新分期显示163例患者中有101例(62%)肿瘤降期,但只有85例患者(52%)接受了切除手术;其中52例(32%)为根治性切除(R0),33例为非根治性切除(R1 - 2)。术后总体死亡率为11.7%(85例中的10例),发病率为41%(85例中的35例)。6例患者有完全病理缓解,另外25例患者显著降期至pⅠ期、ⅡA期或ⅡB期。总体5年生存率为11%(中位生存期11个月)。切除手术后,5年生存率为20%(中位生存期16个月);未缓解患者在未切除的姑息治疗后无1例存活4年(中位生存期5个月)。52例接受R0切除患者的5年生存率为29%(中位生存期23个月)。根据R、pT、pN和p分期分类对患者进行分层,生存曲线与同期587例仅接受手术的“潜在可切除”食管癌B组患者的相应数据相当。此外,与136例之前或之后未接受新辅助治疗的局部晚期肿瘤患者(C组)相比,结果有所改善。在这些患者中,R0切除率为7%,总体5年生存率为3%(中位生存期5个月)。
尽管本研究为非随机研究,但这些结果表明,在局部晚期食管癌中,一线化疗可提高切除率并改善总体长期生存率。在接受R0切除手术的缓解患者中,预后取决于最终病理分期而非初始治疗前分期。