This study clarified the therapeutic efficacy of nodal dissection in locally advanced SGC in the era of surgery alone and in the era of effective adjuvant chemotherapy. Survival for the era of surgery alone indicates the cure rate achieved only by local control and might represent the proportion of tumors limited to the local site. On the other hand, the survival prolongation in the era of effective adjuvant chemotherapy suggests the value of adjuvant chemotherapy for controlling micro-metastases that are not eradicated by surgery. In comparison to the survival of the Former group, the hazard ratio of N0 was 0.873, and that of ND1 and ND2 were 0.789 and 0.565, respectively, in the Latter group. Adjuvant chemotherapy seemed to be more effective in positive for lymph node metastasis cases, especially in ND2 cases. The present study demonstrated that the therapeutic value index improved at almost all stations in the era of effective adjuvant chemotherapy regardless of whether the D1 or D2 nodes were involved and that priority of dissection for #10 ranked high regardless of the era. Taken together, adjuvant chemotherapy would be effective for both the D1 and D2 nodes, especially more effective for D2 nodes. Accordingly, TGS would be more important for locally advanced SGC in the era of effective adjuvant chemotherapy.
SGC is known to have poorer prognosis than common gastric cancer, because of its extreme frequency of peritoneal seeding and lymph node metastases [1, 2]. Focusing on lymph node metastasis, the survivals of ND1 and ND2 were almost similar in the both groups, which was different from the common type; better survival of ND1 than ND2 [13]. These results suggest that the D1 nodes are more 'local' in the common type gastric cancer but they are more 'systemic' in SGC.
How about the efficacy of S-1 adjuvant chemotherapy for SGC? Focusing on the hazard ratio between the Former and the Latter period stratified by N0, ND1, and ND2, S-1 seemed to be more effective in progression with this order; the most effective in ND2 in SGC, which was different from the common gastric cancer cases shown in previous studies. Efficacy of S-1 was more evident in ND1 than in ND2 in the common type in our previous study and was the most evident in N0, followed by ND1 and ND2 in the common type in ACTS-GC trial [13, 14]. These results suggested that S-1 adjuvant chemotherapy is more effective in SGC with lymph node metastasis than without. In this regard, TGS would be justified for locally advanced SGC surgery.
On the other hand, hazard ratio of N0 cases between the Former and the Latter period was 0.873, indicating that S-1 seemed to be less effective for N0 cases in SGC. It is considered that peritoneal recurrence is dominant pattern in N0 cases in SGC, S-1 may be less effective for peritoneal recurrence of SGC. More intensive adjuvant or perioperative chemotherapy, not S-1 alone, may be needed for further improvement of the prognosis of SGC.
The present study was associated with several limitations. First, this study just compared the index based on the metastatic rate and the survival between the Former and the Latter period. In the Latter period, most (but not all) patients received adjuvant chemotherapy including S-1. Ideally, surgery alone should be compared to S-1 adjuvant chemotherapy, which would be only possible by randomized comparison of the ACTS-GC trial; however, this has not been performed. In addition, it is impossible to perform a prospective trial in the era of effective adjuvant chemotherapy. On the other hand, surgeons must determine surgery type before adjuvant chemotherapy regardless of the patients who receive S-1 or not. After surgery, some patients would not receive adjuvant chemotherapy because of morbidity, decrease in organ function, food intake loss, and so on. No one knows whether the patients can receive adjuvant chemotherapy before surgery. The results of the present study would be helpful for surgeons when determining the surgical strategy. Second, the comparison between the two periods includes factors other than the rate of adjuvant chemotherapy administration. The effects of different background factors cannot be ignored. Moreover, the anti-cancer drugs administered after recurrence would have differed between the Former and Latter periods. This factor would have improved survival without S-1 adjuvant chemotherapy. Thus, our results would overestimate the index obtained by effective adjuvant chemotherapy in the Latter period. Third, this is a single-center study. Validation of the present results in a multi-center study may be required. In final, it is difficult to apply this method for cases treated with neoadjuvant chemotherapy. At present, we cannot calculate the therapeutic value index for patients who receive perioperative chemotherapy because the accurate evaluation of preoperative lymph node metastasis is difficult. Therefore, the generalizability of the present results would be limited in areas where perioperative chemotherapy is a standard of care.