Preoperative predictors for early recurrence of resectable pancreatic cancer

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Abstract

Background

The first-line treatment for resectable pancreatic cancer (RPC) is surgical resection. However, our patients have often experienced early recurrence after curative resection for RPC, with desperately poor prognosis. Some reports indicated that minimally distant metastasis not detected at operation might cause early recurrence. The present study aimed to identify preoperative clinicopathological features of early recurrence after curative resection of RPC.

Methods

Ninety RPC patients who underwent curative resection between 2000 and 2014 at our institution were retrospectively analyzed.

Results

Of the 90 patients, 32 had recurrence within 1 year. Univariate analysis demonstrated that preoperative serum carbohydrate antigen (CA19-9) ≥529 U/mL ( P = 0.0011), preoperative serum s-pancreas-1 antigen (SPan-1) ≥37 U/mL ( P = 0.0038), and histological grades G2–G4 ( P = 0.0158) were significantly associated with recurrence within 1 year after curative resection. Multivariate analysis demonstrated that preoperative serum CA19-9 ≥ 529 U/mL ( P = 0.0477) and histological grade G2–G4 ( P = 0.0129) were independent predictors of recurrence within 1 year. Recurrent cases within 1 year postoperatively had significantly more distant metastasis than cases with no recurrence within 1 year ( P < 0.001).

Conclusions

Preoperative serum CA19-9 ≥ 529 U/mL and histological grades G2–G4 were independent predictive factors for recurrence within 1 year after pancreatectomy for RPC. Furthermore, recurrent cases within 1 year had more frequent distant metastasis than cases with no recurrence within 1 year. These results suggest that RPC patients with preoperative serum CA19-9 ≥ 529 U/mL should receive preoperative therapy rather than surgery.

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Most cited references 27

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Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.

Helmut Oettle, Peter Neuhaus, Andreas Hochhaus … (2013)

The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated. To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival. CONKO-001 (Charité Onkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012. After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone. The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up. A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%). Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting. isrctn.org Identifier: ISRCTN34802808.

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Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma.

Alona Muzikansky, Sarah P. Thayer, Andrew Warshaw … (2006)

Different prognostic factors stratify patients with pancreatic adenocarcinoma. The purpose of this study was to determine whether preoperative CA19-9 levels can predict stage of disease or survival and whether a change in preoperative to postoperative CA19-9 or the postoperative CA19-9 predicts overall survival. Four hundred twenty-four consecutive patients with pancreatic adenocarcinoma underwent resection between January 1, 1985 and January 1, 2004. Of the patients with a bilirubin less than 2 mg/dL, 176 had preoperative CA19-9 values, and 111 had pre- and postoperative CA19-9 values. Survival was measured from the first postoperative CA19-9 level measured (median, 39 days) until death or last follow-up. A multivariate failure time model was fit using clinical, operative, pathologic, and adjuvant treatment characteristics, and a categorization was defined by the values and changes in CA19-9 before and after surgery. Of the 176 patients, 128 (73%) had T3 lesions, and 99 (56%) had N1 disease; 138 patients (78%) underwent pancreaticoduodenectomy. Median preoperative CA19-9 levels were lower in N0 patients compared with patients with positive nodes (nine v 164 U/mL, respectively; nonparametric P = .06) and in T1/T2 patients versus T3 patients (41 v 162 U/mL, respectively; P = .03). Median follow-up time (n = 111) was 1.8 years (range, 1 to 12.9 years), with overall actuarial 1-, 3-, and 5-year survival rates of 70%, 36%, and 30%, respectively. Significant predictors of survival on multivariate analysis included a decrease in CA19-9 (P = .0005), negative lymph nodes (P = .001), lower T stage (P = .0008), and postoperative CA19-9 less than 200 U/mL (P = .0007). In patients with pancreatic adenocarcinoma, preoperative CA19-9 correlates with stage of disease. Both a postoperative decrease in CA19-9 and a postoperative CA19-9 value of less than 200 U/mL are strong independent predictors of survival, even after adjusting for stage. CA19-9 levels should be included in a patient's perioperative care and should be considered for prognostic nomograms.

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The prognostic and predictive value of serum CA19.9 in pancreatic cancer

J. L. Humphris, D. Chang, A. Johns … (2012)

Background Current staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to aid clinical decision making are lacking. Despite the availability of the serum marker carbohydrate antigen 19.9 (CA19.9) for over two decades, its precise role in the management of PC is yet to be defined, and as a consequence, it is not widely used. Methods We assessed the relationship between perioperative serum CA19.9 levels, survival and adjuvant chemotherapeutic responsiveness in a cohort of 260 patients who underwent operative resection for PC. Results By specifically assessing the subgroup of patients with detectable CA19.9, we identified potential utility at key clinical decision points. Low postoperative CA19.9 at 3 months (median survival 25.6 vs 14.8 months, P = 0.0052) and before adjuvant chemotherapy were independent prognostic factors. Patients with postoperative CA 19.9 levels >90 U/ml did not benefit from adjuvant chemotherapy (P = 0.7194) compared with those with a CA19.9 of ≤90 U/ml (median 26.0 vs 16.7 months, P = 0.0108). Normalization of CA19.9 within 6 months of resection was also an independent favorable prognostic factor (median 29.9 vs 14.8 months, P = 0.0004) and normal perioperative CA19.9 levels identified a good prognostic group, which was associated with a 5-year survival of 42%. Conclusions Perioperative serum CA19.9 measurements are informative in patients with detectable CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in predicting outcome and response to adjuvant chemotherapy. Future clinical trials should prioritize incorporation of CA19.9 measurement at key decision points to prospectively validate these findings and facilitate implementation.

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Author and article information

Contributors

Kohei Nishio: m1155123@med.osaka-cu.ac.jp

Kenjiro Kimura: kenjiro@med.osaka-cu.ac.jp

Ryosuke Amano: ramano@med.osaka-cu.ac.jp

Sadaaki Yamazoe: zoesada@med.osaka-cu.ac.jp

Go Ohrira: gmiz@med.osaka-cu.ac.jp

Bunzo Nakata: bunzo@med.osaka-cu.ac.jp

Kosei Hirakawa: hirakawa@med.osaka-cu.ac.jp

Masaichi Ohira: masaichi@med.osaka-cu.ac.jp

Journal

Journal ID (nlm-ta): World J Surg Oncol

Journal ID (iso-abbrev): World J Surg Oncol

Title: World Journal of Surgical Oncology

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-7819

Publication date (Electronic): 10 January 2017

Publication date PMC-release: 10 January 2017

Publication date Collection: 2017

Volume: 15

Electronic Location Identifier: 16

Affiliations

[1 ]Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585 Japan

[2 ]Department of Surgery, Kashiwara Municipal Hospital, 1-7-9 Hozenji, Kashiwara City, Osaka 582-0005 Japan

Article

Publisher ID: 1078

DOI: 10.1186/s12957-016-1078-z

PMC ID: 5223494

PubMed ID: 28069033

SO-VID: ab9fd8ec-f7e1-45e6-b833-16349ddbc036

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 5 July 2016

Date accepted : 22 December 2016

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ScienceOpen disciplines: Surgery

Keywords: resectable pancreatic cancer,preoperative predictors,ca19-9,histological grade,tumor diameter

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ScienceOpen disciplines: Surgery

Keywords: resectable pancreatic cancer, preoperative predictors, ca19-9, histological grade, tumor diameter

Preoperative predictors for early recurrence of resectable pancreatic cancer

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Abstract

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Karger: Oncology

Most cited references 27

Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.

Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma.

The prognostic and predictive value of serum CA19.9 in pancreatic cancer

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