Currently, surgery remains the only approach to cure gastric cancer. However, improvement of prognosis by surgical resection alone is limited, and peri-operative chemotherapy is necessary (1). In recent years, several large clinical trials have shown the effectiveness of adjuvant post-operative chemotherapy for gastric cancer (2-4). In contrast, the usefulness of adjuvant pre-operative chemotherapy has not been fully demonstrated.
Wei et al. (2019) reported a successful gastric cancer case in which pre- and post-operative adjuvant chemotherapy was performed (5). They conducted five cycles of SOX chemotherapy, radical gastrectomy concomitant with para-aortic lymph node dissection, hyperthermic intraperitoneal chemotherapy, and six cycles of SOX adjuvant chemotherapy, with no severe adverse effects observed. The final pathological stage was ypT4N3bM1.
The clinical stage of the patient was cT4N2M0. With this initial diagnosis, the case seemed to be a resectable for an experienced surgeon. Therefore, the standard treatment strategy for this patient would be to first perform radical gastrectomy up to D2, followed by S-1 + docetaxel as adjuvant chemotherapy (4). However, if this standard therapy had been applied, this patient would have certainly died of cancer. In this case, pre-operative chemotherapy and extended radical gastrectomy were more suitable treatment strategies.
Pre-operative intensive chemotherapy for patients with tumors that are technically resectable is defined as neoadjuvant chemotherapy (NAC). Currently, the clinical significance of NAC for treating gastric cancer is not known. The advantages of NAC include a high rate of R0 resection and high compliance (6). However, it is unclear whether these advantages are truly effective in gastric cancer. It is difficult to improve the R0 resection rate with NAC in case of gastric cancer where combined resection of invaded adjacent organs can be easily performed. Surgery for esophageal cancer is highly invasive, and the compliance of chemotherapy is reduced post-operatively (7); in contrast, the reduction in compliance after surgery for gastric cancer is not as pronounced as in esophageal cancer, Therefore, it is doubtful that small dose differences can lead to prognostic improvements. NAC also has a disadvantage in that if the cancer does not respond to the therapy, it may become unresectable. NAC should be applied to patients who are not expected to have a good prognosis after routine gastrectomy and adjuvant chemotherapy. Therefore, the usefulness of NAC in gastric cancer has been considered in cancers with bulky lymph node metastases or those with a scirrhous phenotype (8). However, the results from the clinical trial of NAC for large type 3 and type 4 gastric cancers (9) indicated that NAC had no effect in these cases (10). The clinical trial of NAC for bulky nodal metastasis is still in the planning stage, and until the results are obtained, the availability of uniform NAC for gastric cancer with cytotoxic drugs will be unclear.
In the treatment of gastric cancer, factors other than the treatment content, such as the accuracy of pre-operative diagnosis, may affect the prognosis. Unlike breast cancer, for which axillary nodal metastasis can be accurately diagnosed by needle biopsy, the diagnosis of lymph node metastasis of gastric cancer is difficult even with the current multidetector CT scan (11,12). The pre-operative diagnosis in this case was cT4N2M0, but the final pathological diagnosis was ypT4N3bM1, and para-aortic nodal metastasis could not be diagnosed. Many of the nodal metastases of gastric cancer are microscopic metastasis, and diagnosis by CT has its own limits. From the perspective of covering the low diagnostic ability of CT, the strategy of applying NAC and super-extended nodal dissection to bulky nodal metastasis cases is worth considering.
This case eventually progressed to Stage IV. The prognosis is severe, and for some oncologists, chemotherapy is an appropriate treatment and may not be considered a surgical target. However, long-term survival cannot be expected with chemotherapy alone (13). In recent years, with advances in chemotherapy, tumors that were surgically unresectable later became resectable with the reduction or disappearance of metastatic lesions by intensive chemotherapy (14). Conversion therapy can be deﬁned as the surgical treatment for R0 resection after chemotherapy of tumors that were originally regarded as technically or oncologically unresectable, or only marginally resectable (14,15). Recently, the result of an international joint retrospective cohort study examining the outcome of conversion therapy for gastric cancer, named CONVO-GC-1, was reported at the ASCO in 2018 (16). In the study, conversion therapy was performed in 1206 patients, and the mean survival time of R0 resected patients was 56.6 months. This outcome is much better than that in patients treated with chemotherapy alone. Conversion therapy might be a new therapeutic strategy to improve the survival of the patients, especially with R0 resection.
Unfortunately, the long-term prognosis for this patient is unknown. There is no pathological response in the article. Whether via NAC or induction chemotherapy, patients with better pathological response have been reported to have a better prognosis. When performing pre-operative chemotherapy for gastric cancer, it is expected that a method with a high response rate will lead to a good prognosis. In the future, chemotherapy for gastric cancer should also move toward molecular targeted therapy and individualized treatment, which will be useful for improving response rates and underscore the importance of pre-operative chemotherapy.
The author wish to thank the DMR editors for this opportunity of writing this article.
Conflicts of Interest: The author has no conflicts of interest to declare.
Ethical Statement: The authors is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
- Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355:11-20. [Crossref] [PubMed]
- Sasako M, Sakuramoto S, Katai H, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol 2011;29:4387-93. [Crossref] [PubMed]
- Noh SH, Park SR, Yang HK, 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. [Crossref] [PubMed]
- Yoshida K, Kodera Y, Kochi M, et al. Addition of docetaxel to oral fluoropyrimidine improves efficacy in patients with stage III gastric cancer: Interim analysis of JACCRO GC-07, a randomized controlled trial. J Clin Oncol 2019;37:1296-1304. [Crossref] [PubMed]
- Wei Z, Zheng J, Hao T, et al. Advanced gastric cancer with lymph node metastasis successfully treated using multimodal therapy: a case report. Dig Med Res 2019;2:1. [Crossref]
- Yoshikawa T, Rino Y, Yukawa N, et al. Neoadjuvant chemotherapy for gastric cancer in Japan: a standing position by comparing with adjuvant chemotherapy. Surg Today 2014;44:11-21. [Crossref] [PubMed]
- Ando N, Kato H, Igaki H, et al. A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907). Ann Surg Oncol 2012;19:68-74. [Crossref] [PubMed]
- Kodera Y. Neoadjuvant chemotherapy for gastric adenocarcinoma in Japan. Surg Today 2017;47:899-907. [Crossref] [PubMed]
- Terashima M, Yoshiaki I, Mizusawa J, et al. Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer, the short-term safety and surgical results: Japan Clinical Oncology Group Study (JCOG0501) Gastric Cancer 2019;22:1044-52. [Crossref] [PubMed]
- Iwasaki Y, Terashima M, Mizusawa J, et al. Randomized phase III trial of gastrectomy with or without neoadjuvant S-1 plus cisplatin for type 4 or large type 3 gastric cancer: Japan Clinical Oncology Group study (JCOG0501). 2018 ASCO Annual Meeting. J Clin Oncol 2018;36:Abstr 4046.
- Ohashi M, Morita S, Fukagawa T, et al. Evaluation of 64-channel contrast-enhanced multi-detector row computed tomography for preoperative N staging in cT2-4 gastric carcinoma. World J Surg 2016;40:165-71. [Crossref] [PubMed]
- Fukagawa T, Katai H, Mizusawa J, et al. A prospective multi-institutional validity study to evaluate the accuracy of clinical diagnosis of pathological stage III gastric cancer (JCOG1302A). Gastric Cancer 2018;21:68-73. [Crossref] [PubMed]
- Kadowaki 1, Komori A, Takahari D, et al. Clinical Characteristics Associated with Long-term Survival in Metastatic Gastric Cancer after Systemic Chemotherapy. Asian Pac J Cancer Prev 2015;16:5433-8.
- Yoshida K, Yamaguchi K, Okumura N, et al. Is conversion therapy possible in stage IV gastric cancer: the proposal of new biological categories of classiﬁcation. Gastric Cancer 2016;19:329-38. [Crossref] [PubMed]
- Terashima M. Conversion therapy for gastric cancer: who can make conversion as successful as Goromaru? Gastric Cancer 2016;19:685-6. [Crossref] [PubMed]
- Terashima M, Yoshida K, Rha SY, et al. International retrospective cohort study of conversion therapy for stage IV gastric cancer 1 (CONVO-GC-1). J Clin Oncol 2018;36:4042. [Crossref]
Cite this article as: Kinami S. Pre-operative chemotherapy is the key to the next stage of gastric cancer treatment. Dig Med Res 2019;2:34.