Neoadjuvant chemotherapy for gastric cancer. Is it a must or a fake?

Abstract

AIMTo investigate the neoadjuvant chemotherapy (NAC) effect on the survival of patients with proper stomach cancer submitted to D2 gastrectomy.METHODSWe proceeded to a review of the literature with PubMed, Embase, ASCO and ESMO meeting abstracts as well as computerized use of the Cochrane Library for randomized controlled trials (RCTs) comparing NAC followed by surgery (NAC + S) with surgery alone (SA) for gastric cancer (GC). The primary outcome was the overall survival rate. Secondary outcomes were the site of the primary tumor, extension of node dissection according to Japanese Gastric Cancer Association (JGCA) performed in both arms, disease-specific (DSS) and disease-free survival (DFS) rates, clinical and pathological response rates and resectability rates after perioperative treatment.RESULTSWe identified a total of 16 randomized controlled trials comparing NAC + S (n = 1089) with SA (n = 973) published in the period from January 1993 - March 2017. Only 6 of these studies were well-designed, structured trials in which the type of lymph node (LN) dissection performed or at least suggested in the trial protocol was reported. Two out of three of the RCTs with D2 lymphadenectomy performed in almost all cases failed to show survival benefit in the NAC arm. In the third RCT, the survival rate was not even reported, and the primary end points were the clinical outcomes of surgery with and without NAC. In the remaining three RCTs, D2 lymph node dissection was performed in less than 50% of cases or only recommended in the “Study Treatment” protocol without any description in the results of the procedure really perfomed. In one of the two studies, the benefit of NAC was evident only for esophagogastric junction (EGJ) cancers. In the second study, there was no overall survival benefit of NAC. In the last trial, which documented a survival benefit for the NAC arm, the chemotherapy effect was mostly evident for EGJ cancer, and more than one-fourth of patients did not have a proper stomach cancer. Additionally, several patients did not receive resectional surgery. Furthermore, the survival rates of international reference centers that provide adequate surgery for homogeneous stomach cancer patients’ populations are even higher than the survival rates reported after NAC followed by incomplete surgery.CONCLUSIONNAC for GC has been rapidly introduced in international western guidelines without an evidence-based medicine-related demonstration of its efficacy for a homogeneous population of patients with only stomach tumors submitted to adequate surgery following JGCA guidelines with extended (D2) LN dissection. Additional larger sample-size multicentre RCTs comparing the newer NAC regimens including molecular therapies followed by adequate extended surgery with surgery alone are needed.

Patterns of recurrence in adenocarcinoma of the esophagogastric junction: a retrospective study

“…Currently, neoadjuvant chemotherapy and neoadjuvant radiochemotherapy are the hotspots in the field of cancer research. There is also evidence [16][17][18] to indicate that neoadjuvant chemotherapy or neoadjuvant radiochemotherapy can reduce local recurrence of AEG and improve prognosis, but there is still controversy about this treatment [19]. Due to the fear of cancer [20] and concern about complications associated with neoadjuvant therapy, neoadjuvant chemotherapy in our medical center is not smoothly administered.…”

Real-life data on improvement of survival after perioperative chemotherapy versus surgery alone on resectable adenocarcinoma of the stomach – a single-center study

“…This rapid establishment of the concept brought some sceptics into the arena: Reddavid et al, after an analysis of 16 studies in the field, doubts that this benefit also applies to patients with a "pure" (distant) gastric cancer who underwent systematic D2lymphadenectomy [11]. Randomized multicenter trials regarding this particular question are still outstanding.…”

Patterns of recurrence in adenocarcinoma of the esophagogastric junction: a retrospective study

“…Currently, neoadjuvant chemotherapy and neoadjuvant radiochemotherapy are the hotspots in the eld of cancer research. There is also evidence [16,17,18] to indicate that neoadjuvant chemotherapy or neoadjuvant radiochemotherapy can reduce local recurrence of AEG and improve prognosis, but there is still controversy about this treatment [19]. Due to the fear of cancer [20] and concern about complications associated with neoadjuvant therapy, neoadjuvant chemotherapy in our medical center is not smoothly administered.…”