3. Discussion
Although PDAC outcomes have been improving owing to progress in multidisciplinary treatments, the 5-year survival rate remains < 5% 10. As previously reported, approximately 75% of patients with resectable PDAC who have undergone radical resection experience tumor relapse and have an overall survival time of < 30 months 11.
Surgery is usually not indicated for postoperative recurrence of PDAC, except when it occurs in the remnant pancreas 12. In such cases, systemic chemotherapy (such as FOLFIRINOX or combination therapy consisting of GEM + nab-PTX) is preferred13,14. However, surgical treatment may also be considered if chemotherapy is successful and metastasis can be controlled for a sufficient period. Our previous report described a patient in whom long-term survival was achieved via surgery for gallbladder and stomach metastases following surgery for PDAC15.
Recurrence of lung metastases after surgery for PDAC is known to have a better prognosis than recurrence at other sites, and previous studies have reported successful resection of lung metastases. Zheng et al. reported that primary tumor recurrence in the lungs was associated with longer median disease-free survival (15 months) and longer median overall survival after detection (20 months) than any other type of primary recurrence. Moreover, patients with primary recurrence in the lungs have the longest median survival (36 months) among all patients with tumor recurrence 16. Kurahara et al.reported that the median survival time of seven patients with postoperative lung metastases of PDAC who underwent lung resection was 36.5 months, which exceeded that of patients receiving either chemotherapy or the best supportive care 5.
Many case reports on lung metastases of PDAC have shown that local resection prolongs patient survival. Furthermore, a long interval between the initial resection for PDAC and subsequent lung resection has been associated with long-term survival (13-15). However, currently available evidence on the effectiveness of resection for pulmonary metastases of PDAC is insufficient to establish general recommendations, and indications for surgery should be carefully weighed in each case. Okui et al. reported that surgery for lung metastasis should be considered under the following conditions: 1) the patient will be able to tolerate the surgery, 2) the primary lesion is under control, 3) no other metastases are present outside the lungs, and 4) multiple lung metastases can be resected 17.
Brain metastases from PDAC are rare and have poor prognosis. Treatment is usually palliative in these cases; however, a previous study has reported that aggressive surgery can result in long-term survival. Lemkeet al. reported that patients with PDAC who achieved long-term survival were initially treated with cancer-directed surgery with curative intent and had solitary metachronous brain metastasis for which complete (R0) resection followed by adjuvant therapy could be performed. Therefore, surgery for metachronous metastatic PDAC lesions may be considered a viable option in some cases 18. Kumar et al. reported a 9-year survival case after craniotomy6. Matsumoto et al. reported that local resection failed to prolong survival in their patient. However, it improved the patient’s neurological symptoms and allowed him to spend the remainder of his life meaningfully, without neurological deficits19. Therefore, surgical resection may confer benefits to some patients.
In the present case, brain metastases were observed in the right inferior parietal lobule and right cingulate gyrus. The former was the cause of the left hemiplegia, which prompted craniotomy. As a result, neurological symptoms improved significantly and the patient recovered sufficiently to walk unassisted.
Gamma knife treatment was also considered, but craniotomy was chosen for the following reasons: 1) the lesion occurred 11 years after surgery for PDAC, and pathological diagnosis by resection was necessary; 2) the lesion was located in the inferior parietal lobule of the non-dominant hemisphere, was present on the brain surface, and was safely resected; and 3) severe peri-tumor edema worsens after gamma knife treatment. The patient’s days were numbered; therefore, prompt improvement of neurological symptoms was required.
Thirteen of the 31 case reports of pancreatic cancer with brain metastasis retrieved in a PubMed search involved surgical resection. Of the 13 patients who underwent surgery, nine underwent radical resection and four underwent palliative surgery, with some patients in both groups experiencing an improvement in prognosis and quality of life18 19 2021.
A previous report revealed that the incidence of PDAC in patients with brain metastasis and complicated lung metastases was higher than that of overall pancreatic cancer patients (29–37.5% vs. 19.9%). Sasakiet al. reported that lung metastasis may be a risk factor for brain metastasis in patients with PDAC 21.
In the present case, lung resection was performed for lung metastasis 5 years and 5 months post-PpPD, craniotomy was performed for brain metastasis 11 years and 4 months post-PpPD, and GS, GEM + nab-PTX, FOLFIRINOX, and S-1 were administered at various time points during the disease course. Considering the transition in tumor markers in Fig. 6, chemotherapy contributed the most to this patient. However, resection of rapidly growing lung metastases and brain tumors that had caused paralysis had significant effects in prolonging the patient’s life prognosis and maintaining his quality of life. Although the prognosis of PDAC remains poor in some patients, it can be improved using multimodal therapy that combines chemotherapy and local excision.