Completing Multimodal Therapy Curbs Postop Complications in Advanced Gastric Cancer

By Marilynn Larkin

February 27, 2020

NEW YORK (Reuters Health) - In patients with advanced gastric cancer, completing multimodal therapy (MMT) may boost survival by reducing major postoperative complications (POCs), a registry study suggests.

"We know from prior randomized controlled trials that patients with locally advanced gastric cancer have improved survival with MMT compared to surgery alone," Selena Li of Massachusetts General Hospital in Boston told Reuters Health by email. "However, several perioperative trials have demonstrated relatively poor completion of the adjuvant component of treatment."

"In our retrospective study, we demonstrate that the completion of all intended therapy, regardless of treatment regimen, significantly impacts survival," she said.

"Although surgical advances may reduce morbidity, we are currently exploring total neoadjuvant therapy (TNT) as a method to ensure the complete receipt of MMT and potentially improve overall survival," she noted.

TNT involves administering chemoradiation and chemotherapy before surgery to optimize the delivery of systemic therapy aimed at micrometastases.

Li and colleagues analyzed data on 206 patients with locally advanced gastric cancer undergoing curative-intent resection from 2001-2015. The median age was 65; 60% were men; and 79%, white.

As reported in the Journal of the American College of Surgeons, 120 patients underwent surgery followed by chemoradiation, 58 received perioperative chemotherapy, and 28 received TNT. POCs were graded using the Clavien-Dindo (CD) classification, and survival outcomes were compared between groups.

MMT completion rates by intention-to-treat were 47.8% in the upfront surgery group, 47.1% in the perioperative chemotherapy group, and 80.6% in the TNT group.

Minor (CDI-II) POCs occurred in 35% of patients, and major (CDIII-IV) POCs in 18.9%. The occurrence of a minor or major POC was not related to patient demographics or pre-existing comorbidities, type of gastrectomy, extent of lymphadenectomy, or pathologic staging.

At a median follow-up of 37 months, the three-year overall survival for patients with a major, minor, or no POC were 33.3%, 56.9%, and 62.1%, respectively. Major POCs were strongly associated with overall mortality (HR 1.72), while minor POCs were not (HR 1.09).

However, there was no difference in three-year overall survival rates in patients experiencing POCs if they completed all intended MMT.

Non-TNT patients who experienced a major POC were less likely to complete MMT (HR 0.36), and a major POC in had a significant impact on survival (HR 2.76). By contrast, a major POC did not affect survival in patients who completed MMT (HR 1.58).

Summing up, the authors state, "We demonstrated a significant association between the occurrence of a major postoperative complication and failure to complete MMT, (which is) strongly associated with improved overall survival. Our findings suggest that a total neoadjuvant approach allows a greater proportion of patients to complete MMT and can mitigate the long-term reduction in overall survival associated with POCs after gastrectomy."

Li said, "Our institution has already completed a pilot study with 25 patients, demonstrating completion rates >90% with acceptable toxicity profile and favorable rates of R0 resection ( We have planned studies to expand our initial observation and further explore patient and tumor characteristics associated with response and resistance."

Dr. Paul Oberstein, Director of the Gastrointestinal Medical Oncology Program at NYU Langone Health in New York City, commented in an email to Reuters Health, "The biggest concern is that this was a retrospective database that covered a long period of time and therefore it is hard to know if it is relevant for someone who is being treated today."

"This study does not try to show that TNT is better or even as good as the current standard of care, so one cannot make this conclusion," he noted. "The biggest barrier to TNT is that we do not know if it will reduce the number of patients who go to surgery and thus prevent some patients from a potential cure. We do not think this is likely since the chemotherapy is usually well tolerated, but this needs to be demonstrated in a prospective trial before it can be recommended for the average patient."

"At best," he said, "this study suggests that we should consider TNT in patients who may be expected to have a slow recovery or major POC from surgery."

SOURCE: Journal of the American College of Surgeons, online February 6, 2020.