How Should Treatment Before and After Stomach Cancer Surgery Be Decided?

In surgically resectable stomach cancer, outcomes of postoperative preventive radiotherapy and chemotherapy were compared, and chemotherapy outcomes were better.

Today, in early-stage stomach cancers without metastasis , surgeryis an indispensable basic oncological treatment. Depending on tumor stage, part or all of the stomach is removed, and regional lymph nodes are extensively removed during surgery. The surgeon's skill and experience are extremely important. In addition to removing the stomach tumor with clear surgical margins, adequate lymph node clearance (at least D1 and, if possible, D2 dissection) is an important medical detail that improves survival.

Despite all this, stomach cancer by its nature has a high postoperative recurrence risk except at very early stages. Even when surgery removes all regional cancer, remaining local micrometastases and those migrating to other organs cause early recurrence. Therefore, to support successful surgery, preoperative tumor-shrinking (neoadjuvant) and/or postoperative preventive (adjuvant) chemotherapy and radiotherapy are used. Although combined treatments gained acceptance after the 2000s, the optimal sequence and method remain under discussion and investigation.

Over the past 20 years, many clinical trials, new chemotherapy drugs and advances in radiotherapy techniques have not altered the fact that patients' 5-year survival rates are approximately %80 in stage IA, %60 in stage IB, %35 in stage II, in stage 3 %8-20, and in stage IV %7, respectively.

Before and/or after surgery, platinum drugs, anthracyclines, taxanes and fluorouracil have been combined in various regimens tested in different clinical studies. FLOT, EOX, CapeOX, ECF and 5FULV, doublet or triplet treatment combinations, have generally been accepted as recurrence-reducing regimens.

Studies have observed that, because stomach cancer surgery is physically taxing, giving chemotherapy before surgery improves adherence and contributes positively to surgical success and survival. In recent years, the generally accepted approach has been to begin chemotherapy before rather than after surgery, except in very early stages (T1,T2). However, clinical data on this remain insufficient.

In 2003, the INTERGROUP 0169 study gave stomach cancer patients postoperative chemotherapy concurrently with radiotherapy (chemoradiotherapy). This significantly improved survival compared with surgery alone and was accepted as standard because no better treatment strategy was available. However, inadequate surgery in almost half of patients undermined scientific confidence in the study's quality and message. In routine practice, patients' difficulty tolerating chemotherapy with radiotherapy after surgery and completing planned standard treatment has also kept this approach open to question over the years.

Subsequent studies did not fully answer our questions about the choice and timing of chemotherapy and radiotherapy before and/or after stomach cancer surgery.

The Lancet Onclogy in April 2018 published findings seeking answers to these questions from CRITICS , an important study.

In CRITICS, all stomach cancer patients began with preoperative chemotherapy. After surgery, one group continued chemotherapy alone, while the other received chemotherapy concurrently with radiotherapy. Adding radiotherapy to postoperative chemotherapy did not show superiority over chemotherapy alone.

Let us look at the study details together:

Between January 2007 and April 2015, the study enrolled patients with stage 1B to stage 4 stomach or gastroesophageal junction adenocarcinoma, a total of 788 patients.

Patients were randomized into two groups. Both received preoperative and postoperative chemotherapy consisting of a platinum drug, epirubicin and capecitabine, while one group received postoperative radiotherapy concurrently with chemotherapy.

The primary objective was to determine whether, in patients beginning with preoperative chemotherapy, adding postoperative radiotherapy to chemotherapy—combined treatment—would improve survival.

Study results

• Surgery rates were similar in both groups and exceeded %90. All patients undergoing surgery had at least D1 dissection, with an average of 15 or more lymph nodes removed.
• After surgery, only %59 and % 62 of patients, respectively, could receive chemotherapy. The groups had similar proportions undergoing surgery and receiving postoperative chemotherapy.
• The most important result of the study was that, after 61 months of follow-up, median overall survival was 43 months in the chemotherapy arm versus 37 months in the chemoradiotherapy arm. As shown, adding radiotherapy to chemotherapy did not produce superiority.
• Side effects observed before and after surgery were similar in the two arms.

Treatment-related mortality was %2 before surgery, while no deaths occurred with treatments given after surgery.

Conclusion and commentary

After optimal surgery, comparing chemotherapy with chemoradiotherapy showed no improvement in overall survival from the chemoradiotherapy combination. Nonadherence to postoperative treatment was high in both groups. Researchers therefore emphasized that future studies should reassess preoperative treatment strategies to improve treatment success.

In conclusion, this study again called into question the addition of radiotherapy to chemotherapy after successful surgery in stomach cancer patients.

Although far from answering all questions about chemotherapy and radiotherapy as treatments supporting surgery for stomach cancer, this study has provided important information.

Discussing these options with the patient and family before planned stomach cancer surgery, if possible, and making the decision through a multidisciplinary oncology board rather than a single physician will prevent potential problems and give the patient and family confidence.