Postresection CA 19-9 Predicts Overall Survival in Patients With Pancreatic Cancer Treated With Adjuvant Chemoradiation: A Prospective Validation by RTOG 9704

Abstract

Purpose CA 19-9 is an important tumor marker in patients with pancreatic adenocarcinoma. A secondary end point of Radiation Therapy Oncology Group trial 9704 was prospective evaluation of the ability of postresectional CA 19-9 to predict survival. Methods CA 19-9 expression was analyzed as a dichotomized variable (< 180 v ≥ 180) or (≤ 90 v > 90). Cox proportional hazards models were utilized to identify the impact of CA 19-9 expression on overall survival (OS). Actuarial estimates for OS were calculated using Kaplan-Meier methods. Results Three hundred eighty-five patients patients had assessable CA 19-9 levels. The majority had a CA 19-9 level lower than 180 or ≤ 90 (n = 220 and 200, respectively), while 34% were Lewis Antigen negative and 33 (9%) and 53 (14%) patients had levels higher than 180 and higher than 90. When CA 19-9 was analyzed as a dichotomized variable, there was a significant survival difference favoring patients with CA 19-9 lower than 180 (hazard ratio [HR], 3.53; P < .0001). This corresponds to a 72% reduction in the risk of death for patients with a CA 19-9 lower than 180. This was also true for patients with CA 19-9 ≤ 90 (HR, 3.4; P < .0001). Multivariate analyses confirmed that CA 19-9, when analyzed as both a continuous and a dichotomized variable, is a highly significant predictor of OS in patients with resected pancreatic cancer. Conclusion To our knowledge, this is the first phase III trial to perform prospective analysis of CA 19-9 levels in patients treated with adjuvant chemoradiotherapy. It definitively confirms the prognostic importance of postresectional CA 19-9 levels after surgery with curative intent in patients with pancreatic cancer.

Change in CA 19-9 Levels after Chemoradiotherapy Predicts Survival in Patients with Locally Advanced Unresectable Pancreatic Cancer

“…In our study, median time from the end of concurrent CRT to post CRT CA 19-9 was 36 days (range, 0.00-168.81 days). In RTOG 9704, the median time from surgery to the blood draw for postoperative CA 19-9 determination was 45 days (range, 11 to 57 days) as a secondary end point of its phase III study (4). To correct for the variability in the time between CRT and evaluation of the first post CRT CA19-9 value, we chose to measure survival as a time-varying covariate from the time of post CRT CA19-9 measurement rather than from CRT.…”

“…Low postoperative serum CA 19-9 levels and a decrease in serial levels following surgery have been shown to correlate with survival (3). RTOG 9704 demonstrated a prognostic role for postoperative CA 19-9 levels in patients with resectable pancreatic carcinoma following surgery (4). The National Comprehensive Cancer Network recommends measurement of serum CA 19-9 level following surgery prior to the administration of adjuvant therapy.…”

Patients with normal-range CA19-9 levels represent a distinct subgroup of pancreatic cancer patients

“…It has been extensively used as a pancreatic cancer biomarker at various phases of pancreatic cancer management (6,8,9,(11)(12)(13). The recommended upper limit for normal serum CA19-9 expression is 37 U/ml, as determined by the standard deviation of CA19-9 expression in the normal population (11,12,14). Several studies have demonstrated that early-and advanced-stage pancreatic cancer patients with normal serum CA19-9 expression (≤37 U/ml) had a significant survival advantage compared with patients with elevated serum CA19-9 expression (>37 U/ml) (11,14,15).…”

“…The recommended upper limit for normal serum CA19-9 expression is 37 U/ml, as determined by the standard deviation of CA19-9 expression in the normal population (11,12,14). Several studies have demonstrated that early-and advanced-stage pancreatic cancer patients with normal serum CA19-9 expression (≤37 U/ml) had a significant survival advantage compared with patients with elevated serum CA19-9 expression (>37 U/ml) (11,14,15). However, the clinical features of pancreatic cancer occurring with normal CA19-9 levels remain unknown.…”

The role of adjuvant chemoradiation in the treatment of pancreatic cancer

“…Overall, 83 % of patients in CONKO-001 and 65 % of patients in ESPAC-3 had R0 resections, compared to 40 % in RTOG 97-04. Additionally, CONKO-001 excluded patients with postresection CA 19-9 levels greater than 2.5 times the upper limit of normal (90 U/ml), which was shown in separate analyses including RTOG 97-04 [30,31]. A report comparing patients from RTOG 97-04 with pancreatic head tumors, radiotherapy delivered per protocol, and CA 19-9 levels <90 U/ml compares favorably with CONKO-001 (median survival 24 vs. 22.1 months, 5-year overall survival 34 % vs. 21 %), even in the setting of only half the rate of R0 resection in CONKO-001 compared with RTOG 97-04, arguing that high-quality radiation may provide benefit.…”