A case of stage IV gastric cancer with para-aortic lymph node metastasis showing pathological complete response after neoadjuvant chemotherapy
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Stage IV advanced gastric cancer with para-aortic lymph node metastasis (PALM) is considered unresectable. Systemic chemotherapy is the treatment of choice for such tumors, while conversion surgery may be a treatment option in the case chemotherapy is effective but R0 resection is possible. We report a case of stage IV gastric cancer with PALM that showed pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) using S-1, oxaliplatin, and trastuzumab (SOX+HER).
A 69-year-old woman who was diagnosed with type 4 stage IV gastric cancer with PALM underwent five courses of NAC with the SOX+HER regimen. The primary tumor and the PALM shrank after treatment, suggesting that the NAC induced a partial response. We performed a total gastrectomy plus distal pancreaticosplenectomy with para-aortic lymph node dissection. Histological analysis revealed no remnant cancer cells in the primary tumor or the lymph nodes, confirming a pCR. The postoperative course was uneventful, and the patient was discharged on day 14 after the operation. S-1 was started as adjuvant chemotherapy, and the patient remains alive without recurrence 2 months after surgery.
This case shows the possibility of conversion surgery after SOX+HER therapy for stage IV advanced gastric cancer with PALM.
KeywordsGastric cancer Para-aortic lymph node metastasis Conversion surgery Pathological complete response
Para-aortic lymph node metastasis
Para-aortic lymph node dissection
Pathological complete response
S-1, oxaliplatin, and trastuzumab
Gastric cancer is the fifth most common cancer and the third leading cause of mortality among all cancers worldwide . Stage IV gastric cancer with para-aortic lymph node metastasis (PALM) is considered an unresectable metastatic disease, and its prognosis remains poor after isolated surgical treatment . The best clinical practice for patients with clinical PALM has remained controversial for over 10 years . Preoperative chemotherapy was recently adopted by studies, and Japanese oncologists have reported an encouraging 5-year survival rate of 53% for gastric cancer with PALM treated by D2 gastrectomy with para-aortic lymph node dissection (PAND) after neoadjuvant chemotherapy (NAC) . Therefore, according to fifth edition of the Japanese gastric cancer treatment guidelines, in cases of stage IV gastric cancer with limited numbers of PALM and Bulky N without other non-curative factors, surgical resection after NAC is suggested. However, developing a safe and standard D2 plus PAND protocol after chemotherapy remains challenging, and to date, only a few surgeons worldwide have performed it expertly. In the present case, we successfully performed radical surgery after the NAC, and the postoperative histological analysis showed a pathological complete response.
Chemotherapy is considered the primary treatment choice for stage IV gastric cancer, but its prognosis remains poor [2, 5]. Surgery is not routinely recommended except for palliative reasons. Under some conditions, the treatment of clinical stage IV gastric cancer with a single incurable factor, such as PALM, positive lavage cytology, and sole liver metastasis, may be controversial . Lymph node metastases and positive cytology on peritoneal washing as unresectable factors are related to better prognoses after conversion surgery when a partial or complete response to chemotherapy was observed . However, there are no evidence-based NAC regimens for advanced gastric cancer, and clinical trials are now ongoing (JCOG1509).
In the present case, we selected SOX plus trastuzumab therapy as the primary treatment because trastuzumab with cisplatin plus capecitabine or S-1 is the recommended regimen according to several phase II studies in HER-2-positive advanced gastric cancer [7, 8, 9]. Takahari et al. reported the efficacy and safety of combination therapy consisting of trastuzumab plus SOX for patients with HER-2-positive advanced gastric cancer . Indeed, another determining factor is the detection of the best timing to operate (or not operate). Surgery generally occurs when the tumor decreases in size and before it develops drug resistance. For this determinant decision-making step, cooperation between oncologists and surgeons is mandatory for the general management of patients (and not the tumor alone). In the current series, a CT scan showed a partial response against the primary tumor and lymph node metastasis, which made us choose conversion surgery, whereas the efficacy of conversion surgery remains unclear .
Due to the fact that suspicious lymph node enlargement can result from inflammatory lymphadenopathy or malignancy, patients with radiologically overt PALM may have entirely different pathological stages (stage IV or not) that will require completely different treatment strategies. However, the pathological diagnosis of enlarged PAN is difficult. PAN biopsy is an invasive and technically difficult manipulation; thus, it is not typically used for clinical diagnosis of PALM in most institutes. In addition, positive lymph nodes will disappear or shrink after preoperative treatment, which makes it difficult to re-biopsy the original nodes during follow-up. In our series, we found that PALM disappeared with isolated PAN as CR pathologically. Whether surgical resection is needed for stage IV gastric cancer remains controversial [11, 12]. PALM is classified as a relatively early type in stage IV gastric cancer, is associated with a lower tumor burden than other organ and peritoneal metastases, and could be the most suitable surgery type among all types of stage IV gastric cancer . We performed total gastrectomy plus distal pancreaticosplenectomy with para-aortic lymph node dissection in terms of the lymphatic metastasis system of gastric cancer. In the present case, because swollen lymph nodes along with the lesser curvature, celiac artery, splenic artery, and PAN were detected, the en bloc resection of primary lesion and metastatic lymph node tissue by total gastrectomy plus distal pancreaticosplenectomy with para-aortic lymph node dissection was necessary to remove the cancer cells without exposure.
In conclusion, here, we described a case of successful conversion surgery with SOX+HER therapy for stage IV gastric cancer with PAN metastasis. Neoadjuvant therapy with SOX+HER and conversion surgery might be an effective treatment for stage IV gastric cancer with PAN metastasis. Further evidence and prospective clinical trials are required to establish the optimal strategy for stage IV gastric cancer with PAN metastasis.
We would like to thank Editage (www.editage.com) for English language editing.
YK drafted the manuscript. TO and YS edited the article. YK, KO, and TO performed the preoperative investigation and operation. MM diagnosed pathologically. TO provided the academic consideration. All authors read and approved the final manuscript.
This work was supported by Kochi Organization for Medical Reformation and Renewal grants.
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Consent for publication has been obtained from the patient presented in this case report.
The authors declare that they have no competing interests.
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