When Gastric Cancer Vanishes Before Surgery: New Study Maps Who Beats the Odds

For patients diagnosed with locally advanced gastric cancer, the news is often grim: the disease is the fourth most common malignant tumor worldwide and a leading cause of cancer-related death, particularly in Eastern Asia, where many cases are already advanced at diagnosis. Yet a new multicenter study from China offers a striking window into what happens when modern preoperative treatment works so well that surgeons find no tumor at all under the microscope. In the largest real-world analysis of its kind, researchers tracked 488 patients who received neoadjuvant treatment followed by radical surgery, and found that roughly one in six achieved what oncologists call a pathological complete response, or pCR — the complete disappearance of viable cancer cells from both the resected stomach and all examined lymph nodes.

The study, conducted across three academic medical centers — Nanfang Hospital of Southern Medical University, The Sixth Affiliated Hospital of Sun Yat-sen University, and Sun Yat-sen University Cancer Center — collected patients treated between September 2015 and October 2022. All had received chemotherapy or chemotherapy combined with immunotherapy before undergoing gastrectomy. The regimens reflected current standards of care: doublet or triplet combinations of fluoropyrimidine-based and platinum-based chemotherapy, including XELOX, SOX, FOLFOX, and the docetaxel-containing FLOT protocol, with some patients also receiving PD-1 immune checkpoint inhibitors every three weeks. Radiological response was assessed by enhanced computed tomography after two to three cycles using the RECIST 1.1 criteria, and the overall response rate across the cohort reached 48.4 percent.

Of the 488 patients, 80 — or 16.4 percent — achieved a pathological complete response. To ensure the finding was robust, the researchers harmonized tumor regression grading across institutions: because one center used the National Comprehensive Cancer Network classification while the other two applied the American Joint Committee on Cancer 8th edition system, three blinded gastrointestinal pathologists conducted a centralized review of all specimens, resolving discrepancies by panel consensus. The definition was strict — no residual tumor cells anywhere in the resection specimen or in any of the resected lymph nodes. Notably, seven patients who had no residual tumor in the primary lesion still harbored carcinoma in their regional lymph nodes, and all seven fell into the non-pCR group.

The survival signal was dramatic. Patients with pCR had significantly better overall survival and recurrence-free survival than those with residual disease, with neither median overall survival nor median recurrence-free survival reached in the pCR group during follow-up. For non-pCR patients, median overall survival was 62.8 months and median recurrence-free survival was 20.9 months. Recurrence rates diverged just as sharply: only 7.5 percent of pCR patients — six of eighty — relapsed, compared with 40.2 percent of non-pCR patients, or 164 of 408. Across the entire cohort, 170 patients, or 34.8 percent, experienced recurrence after neoadjuvant treatment and surgery.

But the study’s most provocative finding concerns the six pCR patients who did relapse. Every single one of them had received adjuvant therapy after surgery, while none of the seventeen pCR patients who were simply observed after surgery experienced recurrence. The authors are careful not to overinterpret this counterintuitive pattern. They suggest two possible explanations: selection bias, in which clinicians may have reserved adjuvant treatment for patients perceived to be at higher risk, or the development of chemotherapy resistance to the specific adjuvant regimen used. With only six events among eighty patients, the statistical power is limited, and the researchers explicitly caution that this observation should not be read as evidence against adjuvant therapy. Instead, they argue, it underscores the need for better risk stratification to identify the minority of pCR patients harboring residual micrometastatic disease who might genuinely benefit from additional systemic treatment.

The timing and location of relapse told another important story. There was no significant difference between the pCR and non-pCR groups in when or where recurrence occurred, echoing earlier work — including a 2011 cohort study by Fields and colleagues that found 27 percent of pCR gastric cancer patients relapsed within five years. Among all patients with recurrence in the current study, 73.5 percent developed distant metastases, 8.8 percent had local recurrence, and 6.5 percent had both. Of the six relapsed pCR patients, all were male; two developed locoregional recurrence while three developed distant disease involving the peritoneum, distant lymph nodes, or bone, and three of the six died of their recurrence during follow-up.

To predict who might achieve pCR in the first place, the team built a statistical model using logistic regression and a nomogram — a graphical scoring tool that translates patient characteristics into a personalized probability. Multivariate analysis identified radiological response under RECIST 1.1 as a powerful predictor: patients with a complete or partial radiological response had roughly eight times the odds of achieving pCR compared with those with stable or progressive disease. Even more striking, Epstein-Barr virus-encoded RNA positive status carried an odds ratio of 20.65, making EBER positivity the single strongest molecular predictor in the analysis. After excluding variables with too many missing values, the final nomogram incorporated the neoadjuvant treatment regimen and histological type as independent predictors. The model performed well, achieving a concordance index of 0.844 in the training set and 0.820 in the validation set, with calibration curves showing satisfactory agreement between predicted and observed outcomes and decision curve analysis confirming clinical utility.

The immunotherapy question yielded a nuanced answer. Adding immune checkpoint inhibitors to neoadjuvant chemotherapy significantly increased the pCR rate and cut the recurrence rate nearly threefold — 15.1 percent versus 40.3 percent for chemotherapy alone. Yet this did not translate into significantly longer recurrence-free or overall survival, with Kaplan-Meier comparisons showing no statistically significant difference between the two treatment groups. The finding mirrors results from major international trials: the phase III KEYNOTE-585 study demonstrated that pembrolizumab plus chemotherapy significantly raised pCR rates in locally advanced gastric and gastroesophageal junction cancer but failed to significantly improve event-free survival, while the DANTE trial reported promising pathological responses with atezolizumab-based perioperative therapy. The disconnect between pathological response and hard survival endpoints remains one of the field’s central puzzles, and the authors call for research integrating circulating tumor DNA, radiomics, and digital pathology to predict long-term outcomes more accurately.

Beyond pCR, the study identified clear risk factors for recurrence in the broader population: patients with five or more positive regional lymph nodes had nearly four times the recurrence risk, those with poorly differentiated tumors and neurovascular invasion were also at elevated risk, and a high lymph node ratio — above 30 percent — predicted significantly shorter overall and recurrence-free survival. Tumor regression grade itself mattered, with a three-year recurrence-free survival of 66.5 percent for patients with the best regression grades compared with 50.9 percent for those with lesser responses. Intriguingly, among patients with the best regression grades, those who skipped postoperative systemic therapy had a numerically higher three-year recurrence-free survival of 81.4 percent versus 64.4 percent, though the difference was not statistically significant.

The study has limitations the authors acknowledge candidly: its retrospective design invites selection and treatment bias, the small number of recurrence events among pCR patients limits statistical power, center heterogeneity introduced variability in practices and data collection, and the nomogram lacks external validation. Missing data on Lauren classification and PD-L1 combined positive scores further constrained the analysis. Still, as the largest sample of gastric and gastroesophageal junction cancer patients with pCR after neoadjuvant treatment and radical surgery to date, the study delivers a clear message for clinicians and patients alike: a pathological complete response is one of the most favorable outcomes in this disease, associated with dramatically lower recurrence and superior survival, but it is not a guarantee of cure. The role of adjuvant therapy for these patients remains unresolved, and the authors argue that only prospective randomized trials can settle whether additional postoperative treatment helps or harms the patients whose tumors have already vanished.

Subject of Research: Pathological complete response and survival after neoadjuvant treatment of locally advanced gastric cancer

Article Title: Characteristics and survival associated with pathological complete response following neoadjuvant treatment of locally advanced gastric cancer: a multicenter analysis in a real-world setting

Article References: Lai, M.-Y., Luo, D.-D., Chen, S., Yan, X., Tan, W.-Y., Guan, W.-L., Zhou, Z.-W., Zhao, L.-Y., & Qiu, M.-Z. (2026). Characteristics and survival associated with pathological complete response following neoadjuvant treatment of locally advanced gastric cancer: a multicenter analysis in a real-world setting. Holistic Integrative Oncology, 5(1), Article 53. https://doi.org/10.1007/s44178-026-00273-w

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00273-w

Keywords: gastric cancer, pathological complete response, neoadjuvant treatment, immunotherapy, chemotherapy, recurrence, overall survival, recurrence-free survival, nomogram, tumor regression grade, gastroesophageal junction cancer, adjuvant therapy