Original Contribution
Pathologic complete response to neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma is associated with a better prognosis,☆☆

https://doi.org/10.1016/j.anndiagpath.2011.08.005Get rights and content

Abstract

In patients with pancreatic ductal adenocarcinoma (PDA) who received neoadjuvant therapy and pancreatectomy, pathologic complete response (pCR) is rarely observed and the prognostic significance of pCR is not clear. In this study, we identified 11 patients with pCR (2.5%) from 442 patients with PDA who received neoadjuvant treatment and pancreatectomy from 1995 to 2010. There were 6 men and 5 women, with a median age of 61 years. Four patients had either synchronous or history of extrapancreatic cancer. Five patients received neoadjuvant chemotherapy followed by chemoradiation, and 6 received chemoradiation alone. Ten patients had pancreaticoduodenectomy, and 1 had distal pancreatectomy. Scar and chronic pancreatitis consistent with therapy effect were present in all cases (100%). Pancreatic intraepithelial neoplasia (PanIN) 3/carcinoma in situ was present in 5 cases, and PanIN1 and PanIN2 in 5 cases. However, no residual invasive carcinoma or lymph node metastasis was identified in all cases. Follow-up information was available in 10 patients. Follow-up time ranges from 6 to 194 months (median, 63 months). During the follow-up, 3 patients died of other causes, and 1 developed a second primary PDA in the tail of the pancreas at 84 months after the initial pancreaticoduodenectomy and died at 105 months after the initial diagnosis of PDA. The other 6 patients were alive with no evidence of disease. Patients with pCR had a better survival than did those who had posttherapy stage I or IIA disease (P < .001). Patients with PDA who received neoadjuvant therapy and had pCR in pancreatectomy are rare but have a better prognosis.

Introduction

Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States [1], [2]. Only 20% to 30% of patients with PDA have a resectable disease at the time of diagnosis, and 5-year survival rate is less than 5% [3], [4]. Even in patients who undergo surgical resection, the 5-year survival rate is approximately 20%, with a median survival of 12 to 20 months [5], [6]. High rate of local recurrence and distant metastasis are the main causes of dismal prognosis in patients with PDA. Neoadjuvant chemoradiation therapy (CRT) has been used as an alternative to “surgery-first” approach in patients with a potentially resectable disease because of its potential to reduce in tumor volume, to treat micrometastasis, and to increase the likelihood of a complete resection, especially in borderline resectable cases. In a phase II trial of 86 enrolled patients who received neoadjuvant intravenous infusion of gemcitabine (400 mg/m2 weekly, for 7 weeks) plus external beam of radiation therapy (30 Gy in 10 fractions, 3 Gy/d, for 2 weeks), Evans et al [7] reported a median overall survival (OS) of 34 months in 64 of the 86 enrolled patients who underwent pancreaticoduodenectomy and a median OS of 22.7 months in all 86 patients with a 27% 5-year survival rate. Fifty-eight percent of patients in this gemcitabine-based chemoradiation trial showed partial pathologic response, and 2 patients had pathologic complete response (pCR). Similar results have been reported in a phase II trial of neoadjuvant gemcitabine and cisplatin chemotherapy followed by gemcitabine-based chemoradiation in 90 patients [8]. The median OS was 31 months for the 52 patients who completed the neoadjuvant therapy and underwent pancreaticoduodenectomy [8]. A large retrospective study of 466 consecutive patients with PDA who underwent R0 resection (all margins negative by histology) at Mayo Clinic showed a median OS of 25.2 months in the patients who received neoadjuvant CRT compared with the median OS of 19.2 months in the patients who did not receive neoadjuvant CRT (P = .001). Patients who received neoadjuvant CRT had a better 5-year OS (28%) than those who had no neoadjuvant CRT (17%) [9].

Pathologic complete response has been shown to be associated with lower frequencies of local recurrence and better survival in patients with adenocarcinoma of several anatomical sites who received neoadjuvant therapies [10], [11], [12], [13], [14]. In patients with esophageal and gastroesophageal junction adenocarcinoma who received neoadjuvant therapy, 21.7% to 40.5% of them have been reported to have pCR in their subsequent esophagectomy specimens, and pCR is associated with a better 5-year survival rate and a lower risk of recurrence [12], [14]. Similarly, the rates of pCR in patients with rectal cancer who received neoadjuvant therapy are reported to be 13% to 16% [10], [11]. Overall survival and distant recurrence are significantly improved for patients with rectal cancer who achieved pCR [10], [11]. However, the frequency and the prognostic value of pCR in patients with PDA who received neoadjuvant CRT are not clear. In this study, we identified 11 patients with pCR among 442 consecutive patients who had confirmatory tissue diagnoses of PDA and received neoadjuvant CRT and pancreatectomy at our institution from 1995 to 2010. The radiologic, clinical, and pathologic features of the patients with pCR were reviewed. The survival of patients with pCR was compared with 15 patients with posttreatment American Joint Committee on Cancer (AJCC) stage I disease and 85 patients with posttreatment stage IIA disease. Our study showed that pCR was associated with a better OS and a lower frequency of recurrence in patients with PDA who received neoadjuvant therapy.

Section snippets

Study population and histologic evaluation

To identify patients who had pCR in patients with PDA who received neoadjuvant therapy and pancreatectomy, we searched the computerized databases of the Department of Pathology and the prospective pancreatic cancer database maintained at the Department of Surgical Oncology at our institution from 1995 to 2010. We searched for patients who had treatment effect but no residual invasive carcinoma in the pancreatectomy specimen. During this period, 442 patients who had a histologically confirmed

Results

Among the 442 patients who completed neoadjuvant therapy and underwent pancreatectomy from 1995 to 2010, 11 patients (2.5%) with pCR in pancreatectomy specimens were identified. The summary of the clinical presentations, history of prior or synchronous cancer, radiologic findings, values of carbohydrate antigen 19.9 (CA19.9), pretreatment diagnosis by cytology FNA, the types of neoadjuvant therapies, OS, and outcomes of these 11 patients is listed in Table 1. These patients included 6 men and 5

Discussion

In this study, we report the clinical and pathologic features of 11 patients with PDA who completed neoadjuvant chemoradiation and had pCR in posttherapy pancreatectomy specimens. We found that patients with pCR had a better survival than did those patients who had posttreatment stage I or stage IIA disease. Our findings highlight the importance of a careful pathologic evaluation of posttherapy pancreatectomy specimen in predicting the prognosis in this group of patients.

Despite significant

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  • Cited by (0)

    This work was supported by the National Institutes of Health Grant (1R21CA149544-01A1) and the Institutional Research Grant at The University of Texas MD Anderson Cancer Center.

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    There are no financial disclosures from all authors.

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