Dr. Sunnie S. Kim, credit Keith Weller
Dr. Waddah B. Al-Refaie, credit Keith Weller
Question: What is the optimal timing for surgery after neoadjuvant chemotherapy in advanced gastric cancer?
Answer: Perioperative chemotherapy is considered a standard of care for locally advanced, resectable gastric cancer based largely on the results of the British MAGIC and the French FNCLCC/FFCD trials, which showed a significant overall survival benefit in those who had received perioperative chemotherapy compared with those who underwent surgery alone.1-2 Notably, the first results from the CRITICS study were presented during the 2016 ASCO Annual Meeting, and they showed that the addition of adjuvant radiotherapy to perioperative chemotherapy did not improve overall survival compared to perioperative chemotherapy alone. The conclusion is that perioperative chemotherapy is the standard of care in Europe.3
In the MAGIC trial, neoadjuvant chemotherapy helped to downstage tumor burden and improved the likelihood of an R0 resection (79% vs. 70%; p = 0.03).1 Compared to the surgery-only group, those who received neoadjuvant chemotherapy had significantly smaller primary tumors (T1/T2) and less lymph node involvement (N0/N1).1 Chemotherapy was also shown to be better tolerated in the neoadjuvant setting due to better patient performance status compared to the adjuvant setting where patients may have postoperative difficulties.1
Gastrectomy is performed 3 to 6 weeks after completion of the last cycle of chemotherapy. This recommendation is based on empiric evidence from the MAGIC and FNCLCC/FFCD trials, in which surgery was performed 3 to 6 weeks and 4 to 6 weeks after completion of neoadjuvant chemotherapy, respectively. It is unclear whether delayed gastrectomy compromises patient outcomes.
In the time between completion of chemotherapy and surgery, we recommend a number of measures to both select patients who would benefit from gastrectomy, as well as to optimize those patients prior to surgery and adjuvant chemotherapy.
Because gastric cancer is an aggressive solid organ cancer, restaging after neoadjuvant chemotherapy with CT imaging or PET scan is recommended to assess for the presence of interval development of metastatic disease. In select cases, repeat diagnostic laparoscopy (DL) with peritoneal cytology should also be considered, as it can identify occult progression in 7% to 24% of patients with C0 disease prior to neoadjuvant therapy and, thereby, spare them a laparotomy.4-6 The main benefit of DL is its improved sensitivity and specificity rates of 86% and 100% when compared to sensitivities of CT scans (81% to 83%) or that of PET scans (65% to 78%).7-12 It is estimated that DL can identify occult metastases in up to one-third of patients whose disease was considered M0 on preoperative cross-sectional imaging.13
At our institution, MedStar Georgetown University Hospital, we also adopt this timeframe to provide the patient with intensive nutritional counseling. Ideally, the patient will have received nutritional education prior to neoadjuvant therapy. However, the period after the last cycle of chemotherapy and prior to surgery allows for nutritional optimization, further education on operative recovery and post-gastrectomy dietary changes, and an opportunity to mitigate issues related to diminished performance status in preparation for surgery. Nutritional counseling is recognized as a key component of comprehensive cancer care. Meta-analysis of randomized controlled trials has shown that nutritional treatment of weight loss is associated with significant improvements in survival and complication rates.14,15 For gastric cancer, a lean body loss of 5% or more was an independent risk factor for post-gastrectomy complications and the ability of a patient to continue adjuvant chemotherapy.16,17
Timing of gastrectomy after completion of neoadjuvant chemotherapy is guided by the two aforementioned trials, in which surgery was performed 4 to 6 weeks after the last cycle of chemotherapy. We advocate that during this period prior to surgery, one should reassess the benefit of proceeding to gastrectomy by restaging with radiologic imaging and DL. In those patients who do not have further disease progression and for whom gastrectomy is deemed beneficial, measures to optimize their nutritional status have been shown to improve survival and the ability to tolerate adjuvant chemotherapy.