Survival outcomes post radical gastrectomy and D2 lymphadenectomy: Real-world evidence from a tertiary care cancer center.
Authors: Pinninti Rakesh , Pasham Kiran , Mohan M V T Krishna , Ayyagari Santa , Boyyela Pavan , Nusrath Syed , Fonseca Daphne , Patnaik Sujith C. , K Suseela , K V V N Raju , Thammineedi Subramanyeshwar Rao , Rajappa Senthill J. 
Published: July 2024

e16075

Background: Radical gastrectomy and D2 lymphadenectomy (RGD2) are pivotal therapeutic strategies in gastric cancer that enable more accurate staging and offer the potential for a cure. Perioperative systemic therapy compared to surgery alone can improve survival in resectable gastric cancer. In the present analysis we analyzed survival outcomes in patients undergoing RGD2. Methods: This retrospective analysis included a consecutive series of patients who had undergone RGD2 at our hospital between Jan'17 to Dec'22. The primary objective was event free survival (EFS) with "Event" defined as a local/distant recurrence, death from any cause and being "lost to follow-up(LTFU)" for > 18 months since the last followup. Secondary objectives include overall survival (OS), pathological complete response (pCR), safety and tolerability of NACT and ACT. For the study protocol, "completion of planned chemotherapy" (CPCT) is defined as 6 - 8 cycles of FLOT/CAPEOX or 5 - 6 cycles of EOX/DOX/CIS5FU delivered as per the treating physician’s discretion as neoadjuvant (NACT) or adjuvant (ACT) chemotherapy. Results: A total of 207 patients had undergone RGD2 in the study period. The mean age of the cohort is 57.3 yrs (range 28 to 87). At the data cut-off time (14th Oct'23) and at the median follow-up period of 45.8 mths, 120 events had occurred (72 disease recurrence, 29 dead and 19 LTFU) and the median EFS for the entire cohort was 28.0 mths (CI 20.1 - 36.0). In the univariate analysis, EFS was significantly improved in those who had received NACT, ACT, attained CPCT, early pathological stage, absence of LVI or PNI, and negative surgical margins (P < 0.05). In Cox-regression analyses, factors that remained significant for improved EFS were CPCT(HR 0.53, CI 0.33 – 0.83, p 0.007), absence of PNI(HR 0.55, CI 0.34 - 0.90, p 0.016), early pathological stage (HR 0.51, CI 0.29 – 0.88, p 0.016), and margin-negative status(HR 0.38, CI 0.18 – 0.81, p 0.013). For the OS analyses, patients lost to follow-up at the data cut-off time (25/207) were excluded. At a median follow-up of 43.9 mths, mOS for the analyzed cohort was 38.8 mths (CI 28.3 - 49.27). Factors for improved mOS in univariate analyses were CPCT, early pathological stage, negative LVI, PNI, margin, and well-differentiated histology (P < 0.05). In Cox-regression analyses, factors significant for improved OS were negative margin(HR 0.42, CI 0.19 – 0.91, p 0.028), CPCT (HR 0.54 CI 0.32 – 0.93, p 0.026), and early pathological stage (HR 0.30 CI 0.16 – 0.58, p 0.000). For those who received NACT, pCR was 12.1% (20.5% for FLOT). Grade 3 & 4 toxicities, and significant weight loss were noted similarly among those receiving NACT (19.6% & 46.7%) and ACT (17.6% & 49%). Conclusions: There is improved survival in those completing the planned systemic therapy and histological markers of involved margins, PNI and advanced pathological stage negatively impact the survival post RGD2.