Prognostic Impact of Perioperative Serum CA 19-9 Levels in Patients with Resectable Pancreatic Cancer

Background

Pancreatic cancer is one of the most deadly cancers, and serum carbohydrate antigen 19-9 (CA19-9) level has been reported to be a useful prognostic marker in pancreatic cancer. The purpose of this study was to determine which prognostic factor (preoperative or postoperative serum CA19-9 level) is more useful.

Methods

Pre- and postoperative serum CA19-9 levels were measured in 109 patients who underwent surgical resection for pancreatic cancer between 1998 and 2009, and their relationships to clinicopathological factors and overall survival were analyzed with univariate and multivariate methods.

Results

In univariate analysis, tumor location (P = 0.019), postoperative adjuvant chemotherapy (P < 0.001), residual tumor factor status (P < 0.001), UICC pT stage (P = 0.004), lymph node metastasis (P = 0.015), and UICC final stage (P = 0.015) were significantly associated with overall survival. Differences in overall survival were significant between groups divided on the basis of four postoperative CA19-9 cutoff values (37, 100, 200, and 500 U/ml) but not significant between groups divided on the basis of the same four preoperative CA19-9 cutoff values. Pre- to postoperative increase in CA19-9 level also was significantly associated with poor prognosis. In multivariate analysis, postoperative adjuvant chemotherapy (hazard ratio, 1.59; P = 0.004) and postoperative CA19-9 cutoff value of 37 U/ml (HR, 1.64; P = 0.004) remained independent predictors of prognosis.

Conclusions

Postoperative CA19-9 level is a better prognostic factor than preoperative CA19-9 level, and curative surgery for resectable pancreatic cancer should be tried regardless of the preoperative CA19-9 level.     

CA125 is Superior to CA19-9 in Predicting the Resectability of Pancreatic Cancer

Background

Although carbohydrate antigen 19-9 (CA19-9) has been reported as a biomarker to predict the resectability of pancreatic cancer, several limitations have restricted its clinical use.

Methods

The potential of several serum tumor markers (CA19-9, CA125, CA50, CA242, CA724, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP)) to predict the resectability of pancreatic cancer was evaluated by receiver operating characteristic (ROC) analysis in a series of 212 patients with proven pancreatic cancer.

Results

Compared with other tumor markers including CA19-9, CA125 has a superior predictive value (CA19-9, ROC area 0.66, cutoff value 289.40 U/mL; CA125, ROC area 0.81, cutoff value 19.70 U/mL). In addition, for patients with unresectable diseases misjudged by CT as resectable, the percentage of CA125 over selected cutoff value was higher than that of CA19-9 (CA19-9, 70.27 %; CA125, 81.08 %).

Conclusion

CA125 is superior to CA19-9 in predicting the resectability of pancreatic cancer. Aberrant high levels of CA125 may indicate unresectable pancreatic cancer.     

Prognostic Impact of CA 19-9 on Outcome after Neoadjuvant Chemoradiation in Patients with Locally Advanced Pancreatic Cancer

Background

To asses the impact of CA 19-9 and weight loss/gain on outcome after neoadjuvant chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC).

Methods

We analyzed 289 patients with LAPC treated with CRT for LAPC. All patients received concomitant chemotherapy parallel to radiotherapy and adjuvant treatments. CA 19-9 and body weight were collected as prognostic and predictive markers. All patients were included into a regular follow-up with reassessment of resectability.

Results

Median overall survival in all patients was 14 months. Actuarial overall survival was 37 % at 12 months, 12 % at 24 months, and 4 % at 36 months. Secondary resectability was achieved in 35 % of the patients. R0/R1 resection was significantly associated with increase in overall survival (p = 0.04). Intraoperative radiotherapy was applied in 50 patients, but it did not influence overall survival (p = 0.05). Pretreatment CA 19-9 significantly influenced overall survival using different cutoff values. With increase in CA 19-9 levels, the possibility of secondary surgical resection decreased from 46 % in patients with CA 19-9 levels below 90 U/ml to 31 % in the group with CA 19-9 levels higher than 269 U/ml.

Discussion

This large group of patients with LAPC treated with neoadjuvant CRT confirms that CA 19-9 and body weight are strong predictive and prognostic factors of outcome. In the future, individual patient factors should be taken into account to tailor treatment.     

The combination of the serum carbohydrate antigen 19-9 and carcinoembryonic antigen is a simple and accurate predictor of mortality in pancreatic cancer patients

Purpose

The aim of this study was to detect high-performance prognostic biomarkers of pancreatic cancer which would enable the identification of high-risk patients.

Methods

The subjects were 324 patients who underwent radical surgery for pancreatic ductal adenocarcinoma without neoadjuvant therapy. We evaluated the prognostic impact of four perioperative serum tumor markers, including carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). We also evaluated the indices by multiplying the values of two tumor markers (e.g., CA19-9 × CEA).

Results

The preoperative CA19-9 × CEA index had a strong correlation with the prognosis of patients with pancreatic cancer, even when the cut-off was set at the median value. CA19-9 × CEA ≥500 was an independent predictor of mortality (hazard ratio: 1.642, p = 0.021). In the ROC curve analysis of early mortality after surgery, the CA19-9 × CEA index had the highest goodness of fit. The presence of CA19-9 × CEA ≥500 had the largest attributable risk proportion because of its combined high predictive performance and prevalence. The postoperative CA19-9 × CEA index was also a significant predictive marker of mortality.

Conclusion

The CA19-9 × CEA index is a strong prognostic biomarker that could help identify pancreatic cancer patients expected to have a poor prognosis so that they can be administered appropriate multidisciplinary treatment.     

Preoperative Serum CA 19-9 Level as a Predictive Factor for Recurrence after Curative Resection in Biliary Tract Cancer

Background

Complete surgical removal of biliary tract cancer (BTC) offers the only chance of cure; however, long-term survival remains very limited because of frequent recurrence after surgery. The purpose of our study was to evaluate whether the preoperative serum carbohydrate antigen (CA) 19-9 level could predict recurrence after curative resection of BTC.

Methods

We performed a retrospective review of the medical records of patients who were diagnosed with BTC and underwent curative resection. The optimal cutoff value for the preoperative serum level of CA 19-9 that predicted recurrence was determined by a ROC curve. Preoperative and postoperative risk factors for recurrence were evaluated using log-rank test.

Results

A total of 101 patients were eligible for this study. The optimal cutoff value of preoperative serum CA 19-9 level to predict recurrence was 55 U/mL. Forty-five patients (44.6%) experienced recurrence after curative resection with a median follow-up period of 28.4 months. Recurrence occurred in 33 (61.1%) of 54 patients with CA 19-9 levels ≥55 U/mL compared with only 12 (25.5%) of 47 patients with CA 19-9 levels <55 U/mL. The recurrence rate was significantly higher in patients with baseline CA 19-9 serum levels ≥55 U/mL (hazard ratio, 3.282; 95% confidence interval, 1.684–6.395; P < 0.001).

Conclusions

Elevated preoperative serum CA 19-9 was associated with a high risk of recurrence after curative resection of BTC. Different treatment plans might be needed for patients with BTC and high serum levels of CA 19-9.     

Do patient- and tumor-related factors predict the peritoneal spread of pancreatic adenocarcinoma?

Purpose

In pancreatic cancer, the presence of peritoneal carcinomatosis (PC) precludes the possibility of a surgical cure, irrespective of the resectability of the primary tumor. However, peritoneal spread cannot be reliably detected radiographically during preoperative tumor staging.

Methods

The pancreatic adenocarcinoma database of the Tübingen Comprehensive Cancer Center included 29 patients in whom PC was incidentally detected during the surgery. These patients were retrospectively compared for patient- and tumor-related factors with 29 randomly selected patients without PC who underwent curative resection.

Results

Clinical jaundice and diarrhea were more frequently present in patients without PC. The CA 19-9 levels were significantly higher in patients with PC compared to those in patients without PC. No other differences were observed in the patient- or tumor-related factors between the two groups.

Conclusion

In pancreatic cancer patients, markedly elevated CA 19-9 levels may serve as surrogate marker for peritoneal dissemination, irrespective of the local resectability of the tumor. In such patients, laparoscopy should be considered as an additional staging tool to rule out peritoneal carcinomatosis.     

Failure of Normalization of CA19-9 Following Resection for Pancreatic Cancer is Tantamount to Metastatic Disease

Background

Multidisciplinary therapy for pancreatic cancer involves radical resection followed by gemcitabine-based chemotherapy. Carbohydrate antigen 19-9 (CA19-9), when elevated preoperatively, is a useful marker to monitor disease status following resection. However, little has been reported on outcomes of patients in whom CA19-9 never normalizes. We hypothesize that failure of CA19-9 normalization within 6 months is prognostically equivalent to metastatic disease.

Methods

From our pancreatectomy database, we identified 93 patients with pancreatic adenocarcinoma and elevated CA19-9 prior to resection with levels recorded postoperatively. Patients were grouped based on normalization or persistent elevation of CA19-9 at 6 months after resection. CA19-9 levels normalized (≤35 u/ml) after resection in 38 (41%) and remained elevated in 55 (59%). Clinicopathologic characteristics were compared using Student’s t-test and contingency table analyses. Survival curves were constructed using Kaplan–Meier method and compared by log-rank analysis. Cox regression was used to determine predictors of survival.

Results

The two groups had comparable clinicopathologic characteristics except for nodal status and perineural invasion, which were higher in patients with persistently elevated CA19-9. Persistent CA19-9 conferred shorter median overall survival of 10.8 months compared with 23.8 months in patients with normalization (p < 0.001), which persisted when controlling for nodal status. Multivariate analysis demonstrated persistently elevated CA19-9 as the sole statistically significant negative predictor of survival [hazard ratio (HR) 2.20, p = 0.002].

Conclusions

Persistent CA19-9 elevation after pancreatectomy correlates with shorter survival analogous to unresected or metastatic disease and should be regarded as persistent disease regardless of radiographic findings. These patients should be considered for accrual to clinical trials or initiation of alternative therapy.     

Retrospective Evaluation of the Influence of Postoperative Tumor Marker Status on Survival and Patterns of Recurrence After Surgery for Pancreatic Cancer Based on RECIST Guidelines

Purpose

The purpose of this study was to obtain a comprehensive understanding of the impact of postoperative tumor marker (TM) normalization on survival after pancreatectomy for pancreatic carcinoma. We propose the concept of surgical RECIST based on residual tumor and TM status.

Methods

A total of consecutive patients with pancreatic carcinoma underwent pancreatectomy between August 1, 1989, and August 1, 2008. Pre- and postoperative TM values were available for 194 patients. The relationship between TM status, survival, and other clinical and demographic data was determined with univariate log-rank tests and Cox proportional hazards analysis.

Results

Postoperative TM levels remained elevated in 92 patients (47.4%; partial responders). TM levels normalized in 102 patients (52.6%; complete responders). Lymph node metastases, portal vein resection, absence of retroperitoneal clearance, residual tumor, preoperative high CA19-9, and surgical partial response were associated with decreased survival. Nodal stage (P = 0.0227) and surgical RECIST (P = 0.025) were significant predictors of survival. Partial responders had a significantly lower median survival time (P = 0.0008) and significantly higher frequency of hepatic metastasis (P = 0.0299).

Conclusions

Postresection TM normalization is a strong prognostic factor for pancreatic cancer. The efficacy of pancreatic cancer surgery should be evaluated in the context of both local clearance and serum TM kinetics.     

Significance of Serum Tumor Marker Levels in Peritoneal Carcinomatosis of Appendiceal Origin

Background

The significance of tumor markers in patients with appendiceal carcinomatosis is poorly defined. We determined preoperative and postoperative tumor marker levels in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemoperfusion (HIPEC) and examined their association with clinicopathologic features and survival.

Methods

A total of 176 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis had at least 1 tumor marker measured. Marker levels were correlated with tumor characteristics and oncologic outcomes. Kaplan–Meier curves and multivariate Cox regression models were used to identify prognostic factors affecting progression and survival.

Results

At least 1 marker was elevated prior to CRS/HIPEC in 70 % of patients (CEA, 54.1 %; CA19-9, 47.7 %; CA-125, 47.2 %). Among patients with elevated preoperative marker levels, normalization occurred postoperatively in 79.4 % for CEA, 92.3 % for CA19-9, and 60 % for CA-125. Absolute preoperative tumor marker levels correlated with peritoneal carcinomatosis index (PCI) (p < .0002), and the number of elevated markers was associated with PCI and progression-free survival (PFS). Elevated postoperative CEA level was associated with decreased PFS (median, 13 vs 36 months, p = .0008). On multivariate Cox regression analysis, elevated preoperative CA19-9 was associated with shorter PFS (hazard ratio [HR] 2.9, 95 % confidence interval [95 % CI] 1.5–5.3, p = .0008), whereas elevated CA-125 was associated with shorter overall survival (HR 2.6, 95 % CI 1.3–5.4, p = .01).

Conclusions

Most patients with appendiceal carcinomatosis will have at least 1 elevated tumor marker and will normalize following CRS/HIPEC, allowing for ongoing surveillance. CA19-9 is a promising biomarker for early progression following CRS/HIPEC, whereas CA-125 is associated with shorter survival.     

Serum CA 19-9 as a Marker of Resectability and Survival in Patients with Potentially Resectable Pancreatic Cancer Treated with Neoadjuvant Chemoradiation

Purpose

The role of carbohydrate antigen (CA) 19-9 in the evaluation of patients with resectable pancreatic cancer treated with neoadjuvant therapy prior to planned surgical resection is unknown. We evaluated CA 19-9 as a marker of therapeutic response, completion of therapy, and survival in patients enrolled on two recently reported clinical trials.

Patients and Methods

We analyzed patients with radiographically resectable adenocarcinoma of the head/uncinate process treated on two phase II trials of neoadjuvant chemoradiation. Patients without evidence of disease progression following chemoradiation underwent pancreaticoduodenectomy (PD). CA 19-9 was evaluated in patients with a normal bilirubin level.

Results

We enrolled 174 patients, and 119 (68%) completed all therapy including PD. Pretreatment CA 19-9 <37 U/ml had a positive predictive value (PPV) for completing PD of 86% but a negative predictive value (NPV) of 33%. Among patients without evidence of disease at last follow-up, the highest pretreatment CA 19-9 was 1,125 U/ml. Restaging CA 19-9 <61 U/ml had a PPV of 93% and a NPV of 28% for completing PD among resectable patients. The area under the receiver-operating characteristics curve of pretreatment and restaging CA 19-9 levels for completing PD was 0.59 and 0.74, respectively. We identified no association between change in CA 19-9 and histopathologic response (P = 0.74).

Conclusions

Although the PPV of CA 19-9 for completing neoadjuvant therapy and undergoing PD was high, its clinical utility was compromised by a low NPV. Decision-making for patients with resectable PC should remain based on clinical assessment and radiographic staging.     

Serum CA 19-9 Response to Neoadjuvant Therapy is Associated with Outcome in Pancreatic Adenocarcinoma

Background

Baseline carbohydrate antigen 19-9 (CA 19-9) is a useful prognostic marker in pancreatic ductal adenocarcinoma (PDA); however, data on the significance of a change in CA 19-9 following neoadjuvant therapy are lacking.

Methods

All patients receiving neoadjuvant therapy for PDA from July 2010 to February 2013 were retrospectively reviewed. Resection rate, R0 resection rate, need for venous resection, and overall survival were correlated to CA 19-9 response. Fisher’s exact test, Kaplan–Meier survival analysis, and multivariate analysis using Cox regression were used.

Results

A total of 78 patients were studied (21 patients with resectable disease, 40 borderline resectable, and 17 with locally advanced disease). A variety of chemotherapies ± radiation were utilized during the study period. Overall, 56 patients (72 %) had a decrease in CA 19-9 of >50 % with neoadjuvant treatment. In borderline resectable patients, CA 19-9 response of >50 % predicted R0 resection (odds ratio 4.2; p = 0.05). In borderline resectable patients who had an increase in CA 19-9, none of five (0 %) underwent R0 resection compared with 80 % of the remaining cohort (p = 0.001). The complete pathologic response rate was 29 % in patients who had a CA 19-9 response of >90 % versus 0 % in the remaining patients (p < 0.001). A CA 19-9 response of >50 % resulted in improved overall survival (28.0 vs. 11.1 months; p < 0.0001) and was an independent predictor of survival (hazard ratio 0.26; 95 % CI 0.13–0.55; p < 0.0001).

Conclusions

CA 19-9 response to neoadjuvant therapy is associated with R0 resection rate, histopathologic response, and survival. Incorporation of this easily obtainable biomarker into future clinical trials may facilitate more rapid evaluation of novel regimens.     

Prognostic Value of Early Postoperative Tumor Marker Response in Gastric Cancer

Background

The clinical usefulness of tumor markers as predictors of treatment outcome in patients with stomach cancer after radical gastrectomy has been poorly defined. The purpose of this study was to evaluate a comprehensive understanding of the impact of early postoperative tumor marker normalization on survival after gastrectomy.

Methods

Between January 2001 and December 2007, we enrolled 206 patients who had received radical gastrectomy as an initial treatment and had elevated carcinoembryonic antigen (CEA) (>5 ng/mL) or carbohydrate antigen (CA) 19-9 (>37 U/mL) levels. Early tumor marker response was defined as a normalization of preoperative CEA or CA19-9 values 1–2 months after gastrectomy.

Results

The mean patient age was 61 years (range 29–84 years), and 139 patients (67.5 %) were male. Early tumor marker response was identified in 150 of 206 (72.8 %) patients. Of the patients, 49 (23.8 %), 41 (19.9 %), and 116 (56.4 %) were stages I, II, and III, respectively, according to the seventh edition of the American Joint Commission on Cancer (AJCC) staging system. Both disease-free survival (DFS) and overall survival (OS) were significantly longer in patients with tumor marker response compared with nonresponse (61.5 vs. 37.6 months; P = 0.010 and 71.3 vs. 50.9 months; P = 0.008, respectively). Multivariate analyses showed that high CA19-9 level, early tumor marker response, and tumor, node, metastasis classification system stage were independent predictors of DFS and OS (P < 0.05).

Conclusions

Early CEA or CA19-9 normalization after radical gastrectomy is a strong prognostic factor for gastric cancer, especially in patients with high preoperative levels of tumor markers.     

Defining Venous Involvement in Borderline Resectable Pancreatic Cancer

Background

Pancreatic adenocarcinoma impinging the portal and/or superior mesenteric vein (PV-SMV) is classified as borderline resectable, and preoperative chemoradiation is recommended to increase the margin-negative resection rate. There is no consensus about what degree of venous impingement constitutes borderline resectability.

Methods

All patients undergoing potentially curative pancreatectomy for pancreatic adenocarcinoma were reviewed. Venous involvement was classified by preoperative computed tomography according to Ishikawa types: (I) normal, (II) smooth shift without narrowing, (III) unilateral narrowing, (IV) bilateral narrowing, (V) bilateral narrowing with collateral veins.

Results

From 1990–2009, 109 patients underwent resection of pancreatic adenocarcinoma involving the PV-SMV. Seventy-four patients received preoperative chemoradiation, whereas 35 did not. Patients who received preoperative therapy had a significantly longer median overall survival rate of 23 months compared with 15 months for patients without preoperative therapy (P = 0.001). Preoperative chemoradiation was associated with higher R0 resection rate and negative lymph nodes (both P < 0.0001) but did not affect the need for vein resection. When stratified by Ishikawa types, preoperative therapy was associated with improved overall survival among patients with types II and III but not types IV and V. Similarly, the correlation between preoperative therapy and R0 resection rate was observed only among patients with Ishikawa types II and III.

Conclusions

Preoperative therapy for borderline resectable pancreatic adenocarcinoma is associated with higher margin-negative resection and survival rates in patients with Ishikawa type II and III tumors, defined as a smooth shift or unilateral narrowing of the PV-SMV. Patients with bilateral venous narrowing were less likely to benefit from preoperative treatment.     

Frequency and Intensity of Postoperative Surveillance After Curative Treatment of Pancreatic Cancer: A Cost-Effectiveness Analysis

Background

Few data exist to guide oncologic surveillance following curative treatment of pancreatic cancer. We sought to identify a rational, cost-effective postoperative surveillance strategy.

Methods

We constructed a Markov model to compare the cost-effectiveness of 5 postoperative surveillance strategies. No scheduled surveillance served as the baseline strategy. Clinical evaluation and carbohydrate antigen (CA) 19-9 testing without/with routine computed tomography and chest X-ray at either 6- or 3-month intervals served as the 4 comparison strategies of increasing intensity. We populated the model with symptom, recurrence, treatment, and survival data from patients who had received intensive surveillance after multimodality treatment at our institution between 1998 and 2008. Costs were based on Medicare payments (2011 US dollars).

Results

The baseline strategy of no scheduled surveillance was associated with a postoperative overall survival (OS) of 24.6 months and a cost of $3837/patient. Clinical evaluation and CA 19-9 assay every 6 months until recurrence was associated with a 32.8-month OS and a cost of $7496/patient, with an incremental cost-effectiveness ratio (ICER) of $5364/life-year (LY). Additional routine imaging every 6 months incrementally increased total cost by $3465 without increasing OS. ICERs associated with clinic visits every 3 months without/with routine imaging were $127,680 and $294,696/LY, respectively. Sensitivity analyses changed the strategies’ absolute costs but not the relative ranks of their ICERs.

Conclusions

Increasing the frequency and intensity of postoperative surveillance of patients after curative therapy for pancreatic cancer beyond clinical evaluation and CA 19-9 testing every 6 months increases cost but confers no clinically significant survival benefit.     

Prognostic Impact of the Initial Postoperative CA19-9 Level in Patients with Extrahepatic Bile Duct Cancer

Background

The aim of this study was to investigate the prognostic impact of the initial serum postoperative CA19-9 levels in patients with extrahepatic bile duct cancer.

Methods

Data of a total of 143 patients of extrahepatic bile duct cancer with elevated preoperative serum CA19-9 levels (>37 U/ml) who underwent surgery with curative intent were reviewed retrospectively. The patients were divided into the “Normalization group” and “Non-normalization group” (initial postoperative serum CA19-9 ≤37 and >37 U/ml, respectively), and the clinicopathological factors and survival outcomes in these groups were comparatively analyzed.

Results

The cumulative 5-year overall survival (OS) rate and median survival time (MST) were 39.2 % and 42.9 months, respectively, in the Normalization group and 17.9 % and 24.0 months, respectively, in the Non-normalization group (P?<?0.001). Presence of jaundice, a poorer histological differentiation grade (G3–4), lymph node metastasis, and initial postoperative serum CA19-9 level (>37 U/ml) were significant independent predictors of a poor prognosis on multivariate analysis.

Conclusion

Non-normalization of the serum CA19-9 level in the initial postoperative phase is a strong predictor of a poor prognosis and is a useful marker to identify patients who would need additional treatments and stricter follow-up.

     

Prognostic significance of serum CA19-9 levels in resected pancreatic cancer

Twenty-eight patients with histologically proven pancreatic adenocarcinoma were investigated to evaluate the utility of serum CA19-9 levels as a prognostic indicator after pancreatic resection. Three patients were excluded from the study because their serum CA19-9 levels remained normal throughout the course of the disease. Of the remaining 25 patients, those with preoperative serum CA19-9 levels 200U/ml had a better prognosis than those with serum CA19-9 levels >200 U/ml; however, the difference between the two groups was not significant (P=0.13). Serum CA19-9 levels 30 days after pancreatic resection were normalized (37 U/ml) in 11 patients (group A), and the survival rate of this group was significantly higher than that of the group of patients with persistently elevated CA19-9 levels (>37 U/ml) (group B) (P<0.005). Other factors i.e., preoperative CA19-9 values, tumor size, lymph node metastasis, histology, and stage classification showed no significant differences between group A and group B. Univariate analysis of the findings for the 25 patients showed that the stage classification and postoperative CA19-9 levels were of prognostic significance for prolonged survival. Other factors, i.e., gender, age, histology, preoperative CA19-9 levels, location of the tumor, and mode of operation, had no significance as prognostic indicators. Multivariate analysis showed that postoperative CA19-9 level was the only significant independent predictor of poor survival. Postoperative serum CA19-9 level appears to be useful as a prognostic indicator after resection of pancreatic cancer.     

Re-resection for Isolated Local Recurrence of Pancreatic Cancer is Feasible, Safe, and Associated with Encouraging Survival

Background

Local recurrence of pancreatic cancer occurs in 80 % of patients within 2 years after potentially curative resections. Around 30 % of patients have isolated local recurrence (ILR) without evidence of metastases. In spite of localized disease these patients usually only receive palliative chemotherapy and have a short survival.

Purpose

To evaluate the outcome of surgery as part of a multimodal treatment for ILR of pancreatic cancer.

Methods

All consecutive operations performed for suspected ILR in our institution between October 2001 and October 2009 were identified from a prospective database. Perioperative outcome, survival, and prognostic parameters were assessed.

Results

Of 97 patients with histologically proven recurrence, 57 (59 %) had ILR. In 40 (41 %) patients surgical exploration revealed metastases distant to the local recurrence. Resection was performed in 41 (72 %) patients with ILR, while 16 (28 %) ILR were locally unresectable. Morbidity and mortality were 25 and 1.8 % after resections and 10 and 0 % after explorations, respectively. Median postoperative survival was 16.4 months in ILR versus 9.4 months in metastatic disease (p < 0.0001). In ILR median survival was significantly longer after resection (26.0 months) compared with exploration without resection (10.8 months, p = 0.0104). R0 resection was achieved in 18 patients and resulted in 30.5 months median survival. Presence of metastases, incomplete resection, and high preoperative CA 19-9 serum values were associated with lesser survival.

Conclusions

Resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with favorable survival outcome. This concept warrants further evaluation in other institutions and in randomized controlled trials.     

Primary Tumor Resection Following Favorable Response to Systemic Chemotherapy in Stage IV Pancreatic Adenocarcinoma with Synchronous Metastases: a Bi-institutional Analysis

Introduction

Patients with metastatic pancreatic adenocarcinoma have traditionally been offered palliative chemotherapy alone, and the role of surgery in these patients remains unknown.

Methods

A bi-institutional retrospective review was performed for patients with metastatic pancreatic adenocarcinoma who underwent resection of the primary tumor from 2008 to 2013. The primary outcome measured was postoperative overall survival. Secondary outcomes included postoperative disease-free survival and overall survival from the time of diagnosis.

Results

Twenty-three patients were identified who met the study criteria with a median follow-up of 30 months. Metastatic sites included the liver (n?=?16), the lung (n?=?6), and the peritoneum (n?=?2). Chemotherapy included FOLFIRINOX (n?=?14) and gemcitabine-based regimens (n?=?9), with a median of 9 cycles (range 2–31) prior to surgical treatment. Median time from diagnosis to surgery was 9.7 months (IQR 5.8–12.8). Median overall survival (OS) from surgery, disease-free survival, and OS from diagnosis were 18.2 months (95 % CI 11.8–35.5), 8.6 months (95 % CI 5.2–16.8), and 34.1 months (95 % CI 22.5–46.2), respectively. The 1- and 3-year OS from surgery were 72.7 % (95 % CI 49.1–86.7) and 21.5 % (95 % CI 4.3–47.2), respectively.

Conclusion

Resection of the primary tumor in patients with metastatic pancreatic adenocarcinoma may be considered in highly selected patients with favorable imaging and CA 19-9 response following chemotherapy at high-volume centers providing multidisciplinary care. These patients should be enrolled in prospective clinical trials or institutional registries to better quantify the potential benefits of such a strategy.

     

CA19-9 on Postoperative Surveillance in Pancreatic Ductal Adenocarcinoma: Predicting Recurrence and Changing Prognosis over Time

Background

Serum carbohydrate antigen 19-9 (CA19-9) correlates with response to therapy and overall survival (OS) for patients with pancreatic ductal adenocarcinoma (PDAC). This study aimed to define the chronologic relationship between CA19-9 elevation and radiographic recurrence to develop a model that can predict the risk of recurrence (RFS) and prognosis during interval surveillance for patients with resected PDAC.

Methods

A retrospective review examined patients undergoing surgery for pancreatic adenocarcinoma from January 2010 to May 2016. Their CA19-9 levels were classified at diagnosis, after surgery, and at 6-month surveillance intervals. Recurrence was defined by radiographic evidence. The CA19-9 levels were correlated with RFS and OS at every time point using multivariate analysis.

Results

The study examined 525 patients. Five patterns of CA19-9 were identified: normal (“nonsecretors,” 18.5%), always elevated, and high at diagnosis but normal after resection involving three patterns with varied behavior during surveillance. These five patterns had implications for RFS and OS. When elevation of CA19-9, as assessed at 6-month intervals, was analyzed relative to detection of radiographic disease, CA19-9 had poor positive predictive value (average, 35%) but high negative predictive value (average, 92%) for radiographic recurrence. Conditional RFS showed that CA19-9 elevation did not equal radiographic recurrence but predicted subsequent RFS. Additionally, conditional OS showed that CA19-9 elevation alone was predictive at each time point.

Conclusion

This study showed that CA19-9 patterns beyond the post-resection period predict RFS and OS. High CA19-9 frequently is discordant with recurrence on imaging and may precede it by more than 6 months. At each surveillance interval, CA19-9 is predictive of prognosis, which may help in counseling patients and could be used to direct protocols of salvage chemotherapy.

     

Usefulness of serum p53 antibody measurement in colorectal cancer: an examination of 1384 primary colorectal cancer patients

Purposes

Recently, the serum p53 antibody (S-p53Ab) has been used widely in clinical practice as a tumor marker for colorectal cancer (CRC). However, no large-scale studies have examined the usefulness of serial measurements of S-p53Ab or have established the relationship of this parameter with the clinicopathological factors of CRC.

Methods

An ELISA for S-p53Ab was performed for 1384 primary CRC patients, and the results were categorized by the clinicopathological factors.

Results

The S-p53Ab positivity rate was 24.1 %, and was significantly higher in Stage III–IV than in Stage 0–II cases. However, no relationship was seen with the serum carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA19-9) levels. The addition of the S-p53Ab assay to the CEA and CA19-9 measurements increased the overall diagnostic sensitivity to 50.9 % (CEA and/or CA19-9: 37.3 %). In patients who had undergone complete resection, S-p53Ab positivity was associated with a decrease in the relapse-free survival (p = 0.012), but it was not independent prognostic indicator. S-p53Ab positivity had no influence on the cancer-specific survival.

Conclusions

The S-p53Ab positivity rate was higher than the positivity rates for CEA and/or CA19-9 in Stage 0–I CRC patients. Combining the use of the three tumor marker tests is a potentially effective method for detecting even early-stage CRC.