Predicting Adverse Pathologic Features and Clinical Outcomes of Resectable Pancreas Cancer With Preoperative CA 19-9

Abstract

BackgroundWe evaluated preoperative CA 19-9 levels in patients with resected pancreatic cancer to analyze whether they were predictive of clinical outcomes and could help select patients for additional therapy. We hypothesized that elevated CA 19-9 would be associated with worse pathologic findings and oncologic outcomes.MethodsThis study assessed 509 patients with non-metastatic pancreatic adenocarcinoma who underwent resection at our institution from 1995-2011 and had preoperative CA 19-9 recorded. No patients received neoadjuvant therapy. CA 19-9 level was analyzed as a continuous and a dichotomized (> vs. ≤ 55 U/mL) variable using logistic and Cox models.ResultsMedian follow-up was 7.8 years, and the median age was 66 years (33-90). 64% of patients had elevated preoperative CA 19-9 (median: 141 U/mL), that did not correlate with bilirubin level or tumor size. Most patients had ≥ T3 tumors (72%) and positive lymph nodes (62%). The rate of incomplete (R1 or R2) resection was 19%. Increasing preoperative CA 19-9 was associated with extra-pancreatic extension (p=0.0005), lymphovascular space invasion (p=0.0072), incomplete resection [HR (95% CI) 2.0 (1.2-3.5)], and lower OS [HR = 1.6 (1.3-2.0)]. Each doubling in preoperative CA 19-9 value was associated with an 8.3% increased risk of death [HR = 1.08 (1.02-1.15)] and a 10.0% increased risk of distant recurrence [HR = 1.10 (1.02-1.19)]. Patients classified as non-secretors had comparable outcomes to patients with normal CA 19-9.ConclusionsElevated preoperative CA 19-9 level was associated with adverse pathologic features, incomplete resection, and inferior clinical outcomes. Neither tumor size nor bilirubin confound an elevated CA 19-9 level. Preoperative CA 19-9 level may help select patients for additional therapy.

Role of CA 19.9 in the Management of Resectable Pancreatic Cancer: State of the Art and Future Perspectives

“…Using CA 19.9 levels at the cut-off value of 55 U/mL, they found a significant association between this marker and the pT stage. More specifically, CA 19.9 levels higher than the cut-off resulted associated with pT stage ≥ 3 ( p = 0.0005) [ 36 ].…”

The Prognostic Significance of Novel Pancreas Cancer Prognostic Index in Unresectable Locally Advanced Pancreas Cancers Treated with Definitive Concurrent Chemoradiotherapy

“…The advancing literature has established the prognostic value of CA 19-9 in LAPAC patients managed with chemotherapy or C-CRT plus/minus surgery. [16][17][18][19][20][21][22][23] Although different CA 19-9 cutoffs were utilized, results of past investigations confirmed the significant association between higher CA 19-9 levels and reduced survival results in PAC patients. [19][20][21][22][23] Like our study, the researchers of the aforementioned landmark Charité Onkologie 001 (CONKO-001) and RTOG 97-04 randomized trials chose the CA 19-9 ≤ 90 U/mL as the cutoff level for prognostic stratification of such patients.…”

“…[16][17][18][19][20][21][22][23] Although different CA 19-9 cutoffs were utilized, results of past investigations confirmed the significant association between higher CA 19-9 levels and reduced survival results in PAC patients. [19][20][21][22][23] Like our study, the researchers of the aforementioned landmark Charité Onkologie 001 (CONKO-001) and RTOG 97-04 randomized trials chose the CA 19-9 ≤ 90 U/mL as the cutoff level for prognostic stratification of such patients. 16,17 Authenticating the CA 19-9 as a prognostic factor, Choi et al reported that the pretreatment higher CA 19-9 levels were associated with significantly reduced survival outcomes in their three-tiered nomogram consolidating the SUVmax, radiotherapy dose, and CA 19-9 in a gathering of 426 LAPAC patients undergoing C-CRT.…”

“…3,7,9,10,[31][32][33]35 Similarly, CA 19-9 has been extensively studied for its prognostic significance in PAC patients undergoing various oncological treatments, with proven efficacy for accurate prediction of pretreatment tumor stage and resectability status, response to therapy, PFS, and OS outcomes, despite various cutoffs being used in these researches. [16][17][18][19][20][21][22][23] Surprisingly, establishing rational grounds for the present investigation, the blend of these two potent biomarkers had never been tested before for its prognostic significance in unresectable LAPAC patients who underwent exclusive C-CRT albeit SIRI was first formulated for PAC patients and the CA 19-9 demonstrates its chief utility in PACs.…”

“…[16][17][18] Concerning the prognostic value of CA 19-9, several investigations have found a significant association between the diminished survival results and higher CA 19-9 levels, even though variable cutoffs were adopted in these studies. [19][20][21][22][23] In this respect, the researchers of the benchmark Charité Onkologie 001 (CONKO-001) randomized trial used the CA 19-9 ≤ 90 U/mL threshold level for eligibility in their study, which compared adjuvant chemotherapy with gemcitabine against observation in 368 patients undergoing curative-intent resection of PACs. 16 Later the validity of this cutoff was established by the results of the Radiation Therapy Oncology Group (RTOG) randomized Phase III trial 9704 comparing the use of either continuous infusion 5-fluorouracil (5-FU) or gemcitabine before and after concurrent CRT with 5-FU in patients with resected PACs.…”