| Sumario: | Simple Summary: For patients with advanced gastric cancer that cannot be removed by surgery at diagnosis, drug therapy can sometimes shrink the disease enough to make an operation called conversion surgery possible. First-line treatments have expanded from conventional chemotherapy to HER2-targeted drugs and immunotherapy, but the outcomes of conversion surgery across these different strategies are not well described. We reviewed 187 patients treated at a single center, grouped according to their first-line treatment, and examined how often they underwent conversion surgery, their surgical and pathological outcomes, and the factors linked to survival. We also summarized previously published reports to place our findings in context. Complete tumor removal and the type of drug therapy were associated with longer survival, while the patients' general nutritional and inflammatory conditions reflected their overall outlook. These descriptive, single-center findings may help identify patients who are most likely to benefit from conversion surgery. Background/Objectives: First-line therapy for advanced gastric cancer (AGC) has evolved from cytotoxic chemotherapy to HER2-targeted and immune checkpoint inhibitor (ICI)-based regimens, yet conversion surgery (CS) outcomes across these strategies remain poorly characterized. We describe CS outcomes and prognostic factors by first-line strategy at a single center. Methods: We retrospectively reviewed 187 patients with AGC who began first-line therapy from 2011, grouped as cytotoxic (CTX, n = 127), HER2-targeted (trastuzumab, n = 21), or ICI (n = 39). CS was defined as resection after response, including an extended oligometastatic definition (n = 74). Overall survival (OS) was measured from chemotherapy initiation, and prognostic factors were assessed by Cox regression. Results: Median OS was 14.8, 18.9, and 20.9 months for CTX, trastuzumab, and ICI, respectively (p = 0.048). CS rates were comparable (41%, 33%, and 38%; p = 0.794). Pathological response was more pronounced after trastuzumab/ICI (grade 3 and ypStage 0/1; both p < 0.001). Among CS cases, R0 resection (hazard ratio [HR] 0.31) and trastuzumab/ICI therapy (HR 0.37) were independent favorable factors, whereas high inflammatory–nutritional indices (NLR, CAR) were independent poor prognostic factors. OS was comparable between oligometastatic and conventional CS (p = 0.324). Conclusions: In this hypothesis-generating study, response depth tracked tumor biology, whereas survival was determined by R0 resection, targeted/ICI therapy, and host inflammatory–nutritional status—two largely dissociable axes informing biology- and host-based selection of CS candidates for prospective testing.
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