Life science
Medicine, Life science, Pathology

The pattern of residual tumor after neoadjuvant chemotherapy for locally advanced
esophageal cancer and its clinical significance
Department of Gastroenterological Surgery, Graduate School of Medicine
Assistant Professor Tomoki Makino

Researchmap https://researchmap.jp/_-_-_-

Professor Yuichiro DokiResearchmap https://researchmap.jp/ydoki3251

Life science

Abstract
Objectives: To investigate the residual pattern of esophageal
cancer in the esophageal wall after neoadjuvant chemotherapy(NAC) and its clinical significance.
Background: NAC is a standard treatment for locally advanced
esophageal cancer; however, residual tumor patterns in resected
specimens after NAC and their clinico-pathological characteristics
remain unknown.
Methods: One hundred twenty consecutive patients with cT3 ordeeper esophageal cancer underwent curative esophagectomy
after NAC and achieved grade 2 histological responses between
2000 and 2016. Hematoxylin- eosin staining of residual tumor sections revealed 4 remnant categories: Type 1: shallow, Type 2: central, Type 3: deep, and Type 4: diffuse. We examined associations
between these Types and clinico-pathological factors, including
prognosis.
Results: Forty-five (38%) specimens had no residual tumor cells
in the mucosal layer. The adventitia layer displayed the lowest residual tumor cell frequency (18%) among all layers. Types 1, 2, 3,and 4 residual tumor patterns were found in 49 (41%), 33 (28%), 9(8%), and 29 (24%) patients, respectively. Type 4 showed the maximum standard uptake value after NAC; Types 3 and 4 had higher
ratios of venous invasion than Type 1 or 2. Patients with Type 3 or 4
more frequently developed pleural dissemination or distant metastasis than patients with Type 1 or 2. Survival was similar among the4 Types.
Conclusions: After NAC for locally advanced esophageal cancer, the shallow residual tumor pattern was most common, but
approximately 40% of specimens showed no tumor cells in themucosal layer. Deep and diffuse remnant patterns were associatedwith high risks of pleural dissemination and distant metastasis.

Notably, patients with Type 3 or 4 residual tumors more frequently
developed pleural dissemination or distant metastasis, comparedto patients with Type 1 or 2; however, no significant difference insurvival was observed among patients with the 4 residual tumor
types.

▍ Significance of the research and Future perspective
In the present study, we found that the most common residual
tumor pattern after NAC for advanced esophageal cancer was ashallow remnant type. We also found that, in approximately 40%of cases, tumor cells were absent in the mucosal layer, which indicated that it would be difficult to diagnose a clinical CR (completeresponse), based solely on an endoscopic mucosal biopsy afterNAC. Finally, we showed that deep or diffuse remnant types wereassociated with a high positive rate of venous invasion and a highrisk of developing pleural dissemination or distant metastasis aftercurative surgery. To the best of our knowledge, this study was thefirst to evaluate residual tumor patterns after NAC and their associations with clinico-pathological factors, and might contribute to optimizing treatment strategies, and to eventually improving survival
in patients with advanced esophageal cancer▍ Background & Results
NAC is a standard treatment for locally advanced esophageal
cancer; however, residual tumor patterns in resected specimens
after NAC and their clinico-pathological characteristics remain
unknown. In the present study, we evaluated tumor regression
patterns in a total of 120 resected specimens from cT3 or deeper
esophageal cancer that showed grade 2 histological responses toNAC. We found no residual tumor cells in the EP layers in 55.0% ofcases and no residual cancer cells in the mucosal layers in 37.5%of patients. Residual tumor cells were found at a lower frequency(18.3%) in the AD layer than in any other layers. Patients with type2 residual tumors showed higher rates of endoscopic CR diagnosis, and patients with Types 2 and 3 residual tumors showed significantly less macroscopic ulceration, compared to patients withthe other residual tumor types. These findings were consistent withthe pathological examinations of the resected specimens. Types 3
and 4 residual tumors displayed a significantly higher percentage
of venous invasion compared to Types 1 and 2 residual tumors.

P a t e n t
Hashimoto, T; Makino, T; Yamasaki, M. et al. The Pattern of Residual Tumor After Neoadjuvant Chemotherapy for Locally Advanced Esophageal Cancer
and Its Clinical Significance. Ann Surg. 2020 May; 271(5): 875-884. doi: 10.1097/SLA.0000000000003129.
UR
L https://resou.osaka-u.ac.jp/en/research/2018/20190110_2
K e y w o r d esophageal cancer, neoadjuvant chemotherapy, patterns of residual tumor, recurrence site
Tr e a t i s e