Patient and primary tumor characteristics
Using the SEER-Medicare database, 56,820 patients diagnosed with PAC between 1991 and 2005 were identified. After selecting patients based on a combination of CPT and ICD-9 codes, and excluding patients younger than 64 years old and those who were not surgically managed, 6,676 patients remained (). Of the 6,676 patients with PAC, 3,146 patients (47.1%) who underwent an open pancreatic biopsy or other procedures done without curative intent were excluded. Patients who were unstaged, had metastatic disease, and those who did not have histology codes consistent with adenocarcinoma were then excluded, leaving 2,461 patients (4.3% overall) available for analysis.
Demographic and clinical characteristics of the 2,461 patients with resected PAC are outlined in . Mean patient age was 73.2 years (SEM 0.1 years). Most patients were women (n = 1,321; 53.7%), white (n = 2,056; 83.5%), and resided in an urban setting (n = 2,304; 93.6%). The mean age of patients undergoing surgery for PAC increased over time (for 1991–1996, mean age 72.1 years vs for 2003–2005, mean age 74.0 years; p < 0.001). In addition to being older, patients in the later time periods also had more medical comorbidities as indicated by the Elixhauser comorbidity index. Specifically, only 10.4% (n = 59) of patients undergoing surgical resection for PAC from 1991 to 1996 had ≥3 preoperative medical comorbidities, compared with 26.0% (n = 222) of patients undergoing surgery from 2003 to 2005 (p < 0.001). In contrast, there was a decrease in the number of patients with no medical comorbidities from the beginning to the end of the study period (1991–1996: n = 281 [49.5%] vs 2003–2005: n = 210 [24.6%]; p < 0.001). The most common preoperative comorbidities were hypertension (n = 1,132; 46.0%), diabetes (n = 524; 21.3%), and chronic pulmonary disease (n = 322; 13.1%).
Trends in Baseline Demographic and Clinical Characteristics of Patients with Surgically Managed Pancreatic Adenocarcinoma, Surveillance, Epidemiology, and End Results–Medicare, 1991–2005
The most prevalent histology code (n = 1,661; 67.5%) was 8140, corresponding to “adenocarcinoma not otherwise specified” ().18
The majority of patients had regional disease (n = 2,015; 81.9%) as classified by the SEER historic stage and this proportion increased over time (P
= 0.039). Most patients (n = 1,160; 47.1%) had a tumor grade classified as moderately differentiated. Overall, 54.2% (n = 1,333) of patients had lymph node metastasis on final pathologic examination, with an increase in the number of patients with nodal disease identified over time (1991–1996: n = 287 [50.5%] vs 2003–2005: n = 515 [60.3%]; p < 0.001).
Trends in preoperative diagnostic imaging
In the overwhelming majority of cases, CT was the imaging modality of choice (n = 2,255; 91.6%), and MRI (n = 364; 14.8%) and PET (n = 44; 1.8%) were used in only a minority of patients (). Overall use of cross-sectional imaging increased during the time periods examined (p < 0.001), with 94.3% and 24.7% of patients staged with CT and MRI, respectively, in 2003–2005. For MRI, this corresponded to a >10-fold increase from the beginning to the end of the study period (1991–1996: n = 12 [2.1%] vs 2003–2005: n = 211 [24.7%]; p < 0.001). Similarly, use of preoperative diagnostic laparoscopy increased by >5-fold with 15.5% (n = 132) of patients having a laparoscopic staging procedure before their pancreatic resection in 2003–2005 (p < 0.001). Of note, PET scan was used in only 4.4% of patients, even in the most recent time period examined.
Preoperative Staging, Operative Details, and Postoperative Outcomes of Patients with Resected Pancreatic Adenocarcinoma, Surveillance, Epidemiology, and End Results–Medicare, 1991–2005
Patients from a rural area (n = 15; 9.6%) were as likely to be staged with MRI as patients from an urban setting (n = 349; 15.1%) (p = 0.06). Use of PET (p = 0.62) and diagnostic laparoscopy (p = 0.72) was not statistically different in rural vs urban areas. In contrast, patients with ≥3 medical comorbidities were more likely to have undergone an MRI (p < 0.001) or staging laparoscopy (p = 0.039) before pancreatic resection, compared with patients who had fewer comorbidities. There was no statistical difference in the use of PET imaging based up the patient’s comorbidity index (p = 0.06).
Trends in pancreatic operations and perioperative outcomes
Of the 2,461 patients who underwent pancreatic resection for PAC, 1,945 (79.0%) had a pancreaticoduodenectomy (PD), 333 (13.5%) had a distal pancreatectomy, 28 (1.1%) were managed with total pancreatectomy, and 155 (6.3%) had various other pancreatic resections, including partial and near total pancreatectomy (). There were several shifting trends noted in the type of pancreatic operations performed during the time periods examined (). Specifically, the proportion of patients managed with distal pancreatectomy increased over time (1991–1996: 13.2% vs 2003–2005: 15.9%; p = 0.035), but both PD and total pancreatectomy remained stable throughout the study period (both p > 0.05).
The overall proportion of patients who had any postoperative complication was 53.0% (n = 1,304) and did not change appreciably during the study periods examined ( and ). The most common complications were postoperative infection (n = 302; 12.3%), need for a percutaneous drain (n = 246; 10.0%), and postoperative hemorrhage (n = 209; 8.5%). Notably, use of percutaneous drains increased during the study period (1991–1996: n = 43; 7.6% vs 2003–2005: n = 105; 12.3%; p = 0.005). The risk of complication was associated with having ≥3 Elixhauser comorbidities (≥3 Elixhauser comorbidities: 59.8% vs <3 comorbidities: 54.2%; p = 0.025).
Figure 2 (A) Trends in Elixhauser medical comorbidities, postoperative complications, and 30-day postoperative mortality for patients with pancreatic adenocarcinoma (PAC) undergoing pancreatic resection. Star () indicates the overall test for trend across (more ...)
There were 104 deaths within 30 days of surgery (4.2%) and 271 deaths within 60 days (11.0%). Both 30-day () and 60-day mortality decreased during the study period (both p < 0.05). There was no association between perioperative mortality and rural residence, race, or ≥3 Elixhauser comorbidities (all p > 0.05). Patients undergoing a distal pancreatectomy did, however, have a lower risk of 30-day mortality compared with patients undergoing other types of pancreatic operations (odds ratio [OR] = 0.25; 95% CI, 0.07–0.69; p = 0.003). Specifically, patients undergoing a PD had a nearly 4-fold increase in the risk of death at 30 days vs patients undergoing distal pancreatectomy (OR = 3.90; 95% CI, 1.42–10.69; p = 0.008).
Trends in perioperative therapy: adjuvant chemotherapy vs chemoradiotherapy
Approximately one-half of patients (n = 1,243; 50.5%) received some form of adjuvant treatment with a temporal increase in the use of adjuvant therapy during the study period (1991–1996, 40.3%; 1997–2000, 51.8%; 2001–2002, 51.2%; 2003–2005, 56.1%; p < 0.001) (). Only a small number of patients (n = 26; 1.1%) received preoperative chemotherapy. Overall, 33.2% (n = 817) of patients received adjuvant CRT, and 10.2% (n = 251) received adjuvant chemotherapy only (). Of note, although use of adjuvant CRT decreased after 2000 (1991–1996, 26.9%; 1997–2000, 38.2%; 2001–2002, 34.4%; 2003–2005, 33.5%), use of adjuvant chemotherapy only increased during the time periods examined (1991–1996, 6.0%; 1997–2000, 5.8%; 2001–2002, 10.6%; 2003–2005, 15.6%) (p < 0.001) ().
On univariable logistic regression analysis (), patient age, year of surgery, type of pancreatic operation, postoperative complications, and lymph node metastasis were each noted to be associated with receipt of adjuvant therapy (all p < 0.05). Specifically, age 72 years or younger (OR = 1.93; 95% CI, 1.65–2.27; p < 0.001), presence of lymph node metastasis (OR = 1.77; 95% CI, 1.51–2.08; p < 0.001), and those patients who had no postoperative complications (OR = 1.67; 95% CI, 1.41–1.96; p < 0.001) were the most likely to receive some type of adjuvant therapy. In addition, use of adjuvant therapy increased during the time periods examined (1991–1996, referent; 1997–2000, OR = 1.59; 2001–2002, OR = 1.55; 2003–2005, OR = 1.89; p < 0.001). On multivariable analysis, each of these factors remained independently associated with receipt of adjuvant CRT ().
Logistic Regression Analyses of Variables Associated with Receipt of Adjuvant Therapy in Patients with Resected Pancreatic Adenocarcinoma in Surveillance, Epidemiology, and End Results–Medicare 1991–2005
Among those patients who received some type of adjuvant therapy (n = 1,243), factors associated with receipt of adjuvant chemotherapy alone relative to CRT included older patient age (OR = 1.75; p < 0.001), ≥3 medical comorbidities (OR = 1.57; p = 0.007), and time period 2003–2005 compared with 1991–1995 (OR = 2.21; p < 0.001). On multivariable logistic regression analysis, older patient age (OR = 1.60; 95% CI, 1.20–2.13; p = 0.001) and a later time period of pancreatic resection (2003–2005, OR = 2.0; 95% CI, 1.31–3.06; p = 0.001) remained independently associated with an increased likelihood to have received adjuvant chemotherapy alone vs CRT.
Overall median survival of patients with PAC resected with curative intent was 14.0 months (95% CI, 13.2–14.8 months) with 1-, 3-, and 5-year survival of 53.2%, 19.7%, and 12.6%, respectively. There was a modest improvement in the median overall survival during the time periods examined, with an increase in the median survival from 12.0 to 16.0 months (p = 0.005) (). On multivariable Cox regression analysis with adjustment for patient clinicodemographics, including comorbidities and tumor characteristics, receipt of adjuvant therapy was associated with improved survival (p < 0.001). Specifically, receipt of adjuvant CRT relative to no adjuvant therapy (hazard ratio = 0.70; 95% CI, 0.63–0.77; p < 0.001) or chemotherapy only vs no adjuvant therapy (hazard ratio = 0.81; 95% CI, 0.69–0.97; p = 0.018) was associated with a decreased risk of death ().
Figure 3 Multivariable Cox overall survival from the time of the pancreatic resection stratified by receipt of adjuvant therapy. Patients who received any adjuvant therapy (chemoradiation or chemotherapy only) had a lower risk of death than patients who did not (more ...)