The American Cancer Society estimated in 2014 that there were 22,220 new cases of and 10,990 deaths from gastric cancer.1 Over the past two decades, the results of randomized clinical trials have made strides in treatment leading to the use of multidrug chemotherapeutic regimens as well as combined-modality approaches to the treatment of gastric cancer.
Intermediate magnification micrograph of normal gastric mucosa, i.e. inner most layer of the stomach. H&E stain.
Currently, two treatment paradigms for resectable gastric cancer after appropriate initial staging are used: surgery followed by chemotherapy with or without radiation treatment and perioperative chemotherapy (a combination of neoadjuvant and adjuvant treatment). Both approaches lead to an improvement in survival when compared with surgery alone, but likely through different roles. Chemoradiotherapy leads to improved locoregional control, particularly in cases with a positive margin or where a less aggressive lymphadenectomy is performed, whereas perioperative chemotherapy may lead to improved distant disease control. Both are important as gastric cancer recurrence patterns include both locoregional and distant sites of metastases.
Surgical resection followed by adjuvant treatment for gastric cancer is well studied, with multiple randomized clinical trials. The advantages of adjuvant treatment are prompt surgical resection, the avoidance of potential serious chemotoxicity precluding resection, and, most importantly, accurate pathologic staging. Pathologic staging is not only the most important prognostic criterion for patients but also prevents both under- and overtreatment. The Intergroup 0116 trial by Macdonald and colleagues randomized patients, regardless of the extent of surgical lymphadenectomy, to adjuvant 5-fluorouracil-based chemoradiotherapy or observation following resection.2 The results showed an increase in median survival from 27 months (surgery alone) to 36 months in the chemoradiotherapy group, likely due to improvements in locoregional control.
The Adjuvant Chemoradiation Therapy in Stomach Tumors (ARTIST) trial compared adjuvant chemotherapy with capecitabine/cisplatin with adjuvant capecitabine/cisplatin and radiotherapy following surgical resection, including a D2 lymphadenectomy.3 There was no difference in 5-year overall survival (73% in the adjuvant chemotherapy–alone group and 75% in the chemotherapy plus radiotherapy group). Following resection, secondary end-point analysis showed locoregional recurrence to be 7% in patients treated with chemoradiotherapy compared with 13% with chemotherapy alone. The Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer (CLASSIC) randomized a similar patient population to treatment with adjuvant capecitabine/oxaliplatin compared with surgery alone.4 The overall disease-free 5-year survival was 68% for chemotherapy-treated patients and 52% for surgery alone (p = .0015). The subset of patients who benefited the most on subgroup analysis was patients found to have node-positive disease at the time of surgery.5
Next month, we discuss the proposed advantages of neoadjuvant chemotherapy.
1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin 2014;64:9–29.
2. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725–30.
3. Lee J, Lim do H, Kim S, et al. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol 2012;30:268–73.
4. Bang Y-J, Kim YW, Yang HK, et al. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet 2012;379:315–21.
5. Noh SH, Park SR, Yang H-K, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol 2014;15:1389–96.
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Written by Kelly Olino, MD
Department of Surgery, The University of Texas-Medical Branch, Galveston, TX