Should signet-ring cell histology alter the treatment approach for clinical stage I gastric cancer?

Abstract

321 Background: Upfront surgery is standard of care for stage I gastric cancer. Despite this, many clinicians administer preoperative therapy for clinical stage I disease with signet ring cell histology, given its aggressive biology. We aimed to assess the validity of this practice. Methods: The National Cancer Database (2004-2015) was reviewed for pts with non-metastatic signet ring cell gastric cancer who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical stage and pathologic stage. Primary outcome was overall survival (OS). Results: Of 3000 pts, median age was 61 (IQR: 51-70). 34% were clinical stage I (n = 1018) of which 53% received surgery alone (n = 542), 5% perioperative chemotherapy (n = 47), 12% neoadjuvant therapy (n = 125), and 30% adjuvant therapy (n = 304). Median follow-up was 26 mos. For clinical stage I disease, surgery alone was associated with improved median OS (108 mos) when compared to perioperative chemotherapy (80 mos), neoadjuvant therapy (41 mos), or adjuvant therapy (73 mos, all p < 0.001). For pathologic stage I, surgery alone had equivalent survival to perioperative and adjuvant therapy (5-yr OS: 81 vs 82 vs 79%, p = 0.22). Concordance between clinical and pathologic stage I was 56%, specifically, 41% of clinical stage I pts were upstaged to pathologic stage II (44%) and stage III (56%). Adjuvant therapy for these pts was associated with improved median OS compared to pretreatment (perioperative chemotherapy / neoadjuvant therapy) for those upstaged to pathologic stage II (122 vs 37mos, p < 0.001) or stage III (40 vs 18mos, p < 0.001) disease. Conclusions: Our stage-stratified study demonstrates improved survival with upfront surgery for clinical stage I signet ring cell gastric cancer. Despite 41% of clinical stage I pts being upstaged to stage II or III on final pathology, adjuvant therapy offers a favorable rescue strategy, with improved outcomes compared to those treated preoperatively. Surgery alone also affords similar survival for pathologic stage I disease compared to multimodal therapy. This study challenges the intrinsic bias to over-treat stage I signet ring cell gastric cancer.