Gastric cancer is one of the most common malignant tumors in China, second only to lung cancer and liver cancer in terms of mortality. The incidence rate of gastric cancer varies greatly worldwide, with Asia being the most important, and Europe and the United States having relatively lower incidence rates. The location of tumor growth also varies greatly, with tumors in the gastroesophageal junction in Western countries, while tumors in the body and sinus of the stomach are more common in Asian patients.
Recently, research on gastric cancer continues to focus on individualized and comprehensive treatment as the most important development, and the best available treatment decisions are still based on known prognostic factors. Refinement of the surgical approach and rational assessment and short-term evaluation based on the effectiveness of perioperative treatment will remain the main challenges in the coming period.
I. Diagnosis and staging of gastric cancer
The sensitivity of imaging examination of gastric cancer to abdominal metastases is limited, resulting in some patients with gastric cancer with abdominal metastases being undiagnosed. The emergence of laparoscopic exploration has compensated for the disadvantage of imaging examination. The results of a study from MDAnderson and MSKCC showed that the presence of abdominal metastases was confirmed by laparoscopic exploration in about 23%-31% of patients with progressive gastric cancer.
Since 2012, NCCN guidelines have recommended diagnostic laparoscopic staging and abdominal free cancer cell detection for patients with radical resectable disease. One study reported that the overall sensitivity of laparoscopic staging for the determination of distant metastases was 89%, the specificity was 100%, and the diagnostic accuracy was 95.5%; the sensitivity for lymph node metastases was 54.5%, the specificity was 100%, and the accuracy was 64.3%. The application of laparoscopic staging allows for more accurate staging and a reasonable treatment plan for patients, reducing the possibility of blind open abdomen.
In laparoscopic exploration, the positive rate of node-free metastatic nodes in the naked eye and free cancer cells in the abdominal cavity was about 32%. Therefore, laparoscopic exploration combined with abdominal free cancer cell testing can effectively improve the accuracy of pre-treatment staging. However, there is no standard method for abdominal free cancer cell detection, and cytology is the most commonly used method at present. However, the sensitivity of cytological examination is low and the accuracy of the determined results can be affected by many factors, while the RT-PCR test with higher accuracy requires long time and cannot wait for the results intraoperatively.
Therefore, there is a need to investigate a method for detecting free cells in the abdominal cavity that is both accurate and rapid. There is a recent study in Japan to improve the sensitivity of detecting abdominal metastatic nodules by photodynamic methods, but it is still limited by the limitations of cytological examination. Therefore, the establishment of an accurate and rapid detection method is necessary to enable the results of abdominal cavity free cytology to be widely used in clinical treatment for the benefit of patients.
II. Surgical treatment of gastric cancer
(I) Endoscopic treatment
Lymph node metastasis of gastric cancer is related to tumor size, infiltration depth and differentiation degree. Therefore, the rate of lymph node metastasis of early gastric cancer is low, and the rate of lymph node metastasis of early gastric cancer within mucosa is only 0-5%, which provides an opportunity for endoscopic treatment of early gastric cancer.
Endoscopic treatment of early gastric cancer mainly includes endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). With strict selection of indications, the 5-year survival rate between open and endoscopic surgery for early gastric cancer is not statistically significant and is above 90%.
The Japanese Gastric Cancer Association has established the indications for surgery for EMR.
①Good differentiation;
② ≤20mm mass type tumor;
③≤10mm depressed tumor;
④No ulcer;
⑤ Intramucosal carcinoma. In 2012, the results of a multicenter study in Japan showed that ESD surgery for early gastric cancer is a safe and effective treatment: the complete resection rate is 93.6%, and the complete resection rate is related to the location and size of the tumor, which is more difficult to be resected if the tumor is located in the fundus or the tumor diameter is larger than 2 cm. It should draw our attention.
(II) Laparoscopic surgery
Laparoscopic gastric cancer surgery not only serves as an effective supplement to conventional examination means in diagnosis, but also is gradually recognized in treatment. A 2012 Meta-analysis study showed that the long-term results of laparoscopic-assisted radical resection of distal gastric cancer in early gastric cancer were comparable to those of open surgery, and the complications, length of stay and cost of surgery were less than those of the open group. Therefore, laparoscopic surgery is considered to be the first choice for early gastric cancer treatment.
In 2012, the results of a single-center retrospective study in Japan showed that the 5-year recurrence-free survival rates of 167 patients with stage T1-2 gastric cancer who underwent laparoscopic versus open D2 surgery were 89.6% and 75.8%, respectively, and the 5-year overall survival rates were 94.4% and 78.5%, respectively. 94.4% and 78.5%, respectively, with no statistical difference.
Therefore, Hamabe concluded that laparoscopic D2 radical surgery is comparable to open surgical tumor treatment. Similarly, the Korean KLASS Study Group found in a large retrospective study in 2012 that the 5-year survival rates for progressive gastric cancer undergoing laparoscopic surgery, with more than 2/3 of the patients undergoing radical D2 surgery, were 90.5% (stage Ib, n=86), 86.4% (stage IIa, n=53), 78.3% (stage IIb, n=44), 52.8% (stage III stage a, n=24), 52.9% (stage IIIb, n=24), and 37.5% (stage IIIc, n=8), similar to the previously reported results of open surgery.
This further confirms the effectiveness of laparoscopic treatment of progressive gastric cancer. A recent multicenter study in Canada had similar findings: there was no statistical difference in 3-year disease-free survival and overall survival rates between laparoscopic and open treatment of progressive gastric cancer with postoperative radiotherapy.
Although most of the current domestic and foreign literature is retrospective analysis and there is a lack of large sample and high-quality clinical studies to confirm the effectiveness of laparoscopy in the treatment of progressive gastric cancer, in terms of application prospect, with the improvement of laparoscopic instruments and the accumulation of experience and operational skills of surgeons, laparoscopic radical gastric cancer treatment can be well carried out and the indications will be expanded.
(iii) Open surgery treatment
Different gastrectomies can be used according to the location and extent of gastric cancer. The latest Japanese statute for the treatment of gastric cancer states that for stage T1 tumors in the upper part of the stomach and more than 1/2 of the stomach can be preserved, a major proximal gastrectomy can be performed, and the rest can be performed by total gastrectomy. For lower and middle gastric cancers, it was found that the complication rate after distal gastrectomy was significantly lower than that of total gastrectomy, but it did not affect the survival outcome. Therefore, distal major gastrectomy should be the preferred procedure for lower gastric cancer as long as the proximal margin is ensured to be negative.
Reasonable and effective lymph node dissection is an important part of the surgical treatment of progressive gastric cancer, but the extent of lymph node dissection has always been under constant debate and exploration. With the recent publication of some research results, there is a convergence of views on the extent of lymph node dissection in the East and West: D2 lymph node dissection is a reasonable treatment modality for progressive gastric cancer, and the NCCN guidelines for gastric cancer also include D2 lymph node dissection as the recommended procedure for progressive gastric cancer.
Studies have also been conducted on the effect of lymph node dissection beyond D2. The Japanese JCOG9501 study conducted a multicenter prospective randomized study of D2 radical surgery versus expanded radical surgery (D2 + parietal aortic lymph node dissection) in progressive gastric cancer showed no difference in 5-year survival between the two groups, thus suggesting that lymph node dissection beyond D2 should not be used as a routine procedure.
For combined organ resection, the importance of No. 10 lymph node dissection is emphasized at the time of total gastrectomy, and experienced centers or physicians are advised to adopt No. 10 lymph node dissection with preservation of the spleen and pancreatic body tail, and preservation of the spleen can greatly reduce surgical complications. Only lesions with splenic infiltration or tumors located in the greater curvature of the stomach with 4sb lymph node metastasis should be considered for total gastrectomy combined with splenectomy.
In addition, regarding the question of whether the small omental sac should be removed, a retrospective randomized controlled study in Japan in 2011 yielded an interim analysis: the 3-year survival rates in the group of patients with stage T2-3 progressive gastric cancer who underwent omental sac resection versus the unresected group were 85.6% and 79.6%, respectively, with no statistical difference. For cases invading the plasma layer, the 3-year survival rates were 69.8% and 50.2% in the resected and unresected groups, respectively, and the postoperative peritoneal recurrence rates were 8.7% and 13.2%.
Although there was no statistical difference between the two groups, from the results, we can still see that the therapeutic effect of resection of the omental bursa on progressive gastric cancer, especially tumors with plasma membrane invasion, cannot be ignored.
III. Perioperative treatment
(I) Perioperative chemotherapy
The most representative clinical study on perioperative chemotherapy is the European MAGIC study (Medical Research Council Adjuvant Gastric
Infusional Chemotherapytrial) and the French FFCD study. Meanwhile, neoadjuvant therapy for gastric cancer has also been extensively explored in Japan. The results of a Japanese multicenter phase II clinical study exploring neoadjuvant chemotherapy with the DCS regimen (docetaxel + cisplatin + S-1) in patients with locally progressive gastric cancer were presented at the 2011 ASCO Annual Meeting.
The current disease control rate was 100%, the overall remission rate was 75%, and after neoadjuvant therapy, 68.4% of patients had downgraded pathological stage and the R0 resection rate reached 92.3%. The vast majority of patients treated postoperatively with adjuvant chemotherapy with S-1 alone or an S-1-containing regimen achieved 3-year PFS and OS rates of 87.1% and 91.1%, respectively. neoadjuvant treatment with the DCS regimen showed very high remission, staging downgrade and R0 resection rates, leading to encouraging results.
In 2012, another JCOG1002 phase II clinical study is underway with the primary objective of observing the efficacy and safety of preoperative DCS chemotherapy in gastric cancer patients with extensive lymph node metastases, with promising results. in late 2011, the results of a Canadian multicenter phase II clinical study on perioperative chemotherapy with DCF (docetaxel + cisplatin + 5-Fu) showed that DCF perioperative chemotherapy improved the surgical cure rate and the 3-year survival rate after surgery was 60%. Although survival is still lower than the results of the Japanese study, it confirms the effectiveness of perioperative chemotherapy with the DCF regimen.
(ii) Postoperative adjuvant chemotherapy
Chemotherapy has also been extensively studied as the main method of postoperative adjuvant therapy. The Japanese ACTS-GC study and the Korean CLASSIC study are the most representative recent clinical studies in Asia. The role of postoperative adjuvant chemotherapy has been confirmed through large sample, multicenter clinical studies.
The latest results of the CLASSIC study were presented at the 2011 American Society of Clinical Oncology (ASCO) annual meeting and in Lancet 2012, which confirmed that for patients after radical D2 surgery for stage II/III gastric cancer, postoperative adjuvant therapy with the XELOX regimen significantly prolonged patient disease-free survival, with 3-year disease-free survival rates of 74% in the postoperative chemotherapy group and 59 percent (HR=0.56, P<0.0001), but did not show a significant improvement in overall survival.
By comparing these two studies, we can see that the results of the CLASSIC study more confirm that postoperative xelox adjuvant therapy delays recurrence in patients, whereas the ACTS-GC study showed that s-1 monotherapy adjuvant therapy may provide a benefit in overall survival for gastric cancer patients.
(iii) Perioperative radiotherapy
Postoperative radiotherapy has been the treatment modality promoted in the West, especially in the United States. The 2012 update of the INT-0116 study showed that for patients with gastric cancer with T3 and above and/or lymph node metastases, postoperative radiotherapy improved survival compared with the observation group. 1.51 (95% CI1.25 to 1.83; P<0.001).
The results of the Korean artist study also showed that the postoperative radiotherapy group (capecitabine + cisplatin + radiotherapy) did not prolong disease-free survival compared with the postoperative chemotherapy group; however, a subgroup analysis of cases with lymph node metastases found that the postoperative radiotherapy group improved disease-free survival (p=0.036). Subsequently, further artist-studies are in active preparation. At the 2012 asco annual meeting leong announced a global multicenter clinical study – topgear. this study is comparing the effect of preoperative radiotherapy and chemotherapy and is planned to enroll more than 700 patients. the enrollment has already started and the results are expected.
IV. Conclusion
Comprehensive treatment based on surgery is the development direction of gastric cancer treatment. New chemotherapy regimens, new radiotherapy techniques and reasonable methods of new adjuvant treatment should be continued to be explored on the basis of standardized surgical modalities. Meanwhile, the rational application of these traditional means, preoperative and postoperative nutritional support, and the continuous development of biological therapy will improve the postoperative survival quality of patients and help to increase the survival rate of patients. We believe that with the further development of research, the treatment of gastric cancer will eventually achieve a standardized, individualized and comprehensive treatment model.