Abstract
This retrospective study included 92 consecutive patients with locally advanced or metastatic pancreatic cancer treated in the Turku University Hospital in 2010. The diagnosis of pancreatic cancer was verified by either histological samples (adenocarcinoma) or by imaging or both, excluding other known histological types of tumours. Median patient survival was 11 months. Smokers had a better median overall survival (20 months) than non-smokers (10 months) (p=0.029). Patients with carcinoma of the head of pancreas had the best survival rates (15 months), whereas those with cancers of the tail of pancreas reached a median survival of only 3 months. The importance of this small trial resides in its retrospective and non-randomized nature, analyzing real-life patients, as encountered in daily practice, out of which, unfortunately, a substantial proportion would not be eligible for any randomized clinical trial.
Pancreatic adenocarcinoma, commonly referred to as pancreatic cancer (PC), is the fourth leading cause of cancer-related deaths in Western countries (1). PC is often asymptomatic in the early stages, or it can cause non-specific symptoms such as asthenia, abdominal pain and weight loss (2). Therefore, diagnosis is often delayed, precluding the possibility for radical surgery. Moreover, the 5-year survival rate is less than 10% even after radical surgery (3). When all stages of the disease are included, the overall 5-year survival rate is less than 5% (1, 2).
Several factors are associated with an increased risk of PC. The correlation between cigarette smoking and PC has been confirmed in several epidemiological studies (4, 5). About 20% of PCs are related to smoking. Approximately 7-10% of the patients have a family history of the disease. Other risk factors include age, male sex, chronic pancreatitis, diabetes mellitus, obesity, a high-fat diet, and alcohol intake as well as non-O blood type (6, 7).
Gemcitabine still remains the mainstay of treatment for most patients with advanced disease (8). Combination of gemcitabine with erlotinib may benefit some patients (9), whereas no statistically-significant benefit for gemcitabine doublets in terms of overall survival has been shown in randomized prospective trials (9, 10). Recently, a French trial comparing a triple-combination of fluorouracil, oxaliplatin and irinotecan with single-agent gemcitabine showed encouraging results in favour of the triple-combination, however at the expense of increased toxicity (12). Similarly, the interim of phase I/II and III trials investigating the efficacy of gemcitabine and nab-paclitaxel against single-agent gemcitabine are promising and final results are pending (13, 14).
Patients and Methods
For the present study, we screened 92 consecutive patients from our hospital medical records, who had been diagnosed with locally advanced or metastatic pancreatic cancer and who were treated at the Department of Oncology, Turku University Hospital during 2010. Patients diagnosed with other histological types of cancer, e.g. neuroendocrine tumours, were excluded from this study. The current cohort consisted of 70 patients with either histological or radiological diagnosis of pancreatic adenocarcinoma, including 37 women and 33 men. Patient age varied 43-87 years, median of 68 years. Out of these patients, two (3%) had a family history of pancreatic cancer and 26 (37%) of other types of cancer, including breast, colorectal, lung, gastro-oesophageal, prostate and gynecological malignancies. The tumour was located in the head in 52 (74%) patients, in the tail in 9 (6%) patients and in the body of pancreas in 7 (10%) patients. Distant metastases were present among 22 (31%) patients, while 36 (51%) had a locally advanced disease at diagnosis. A total of 24 (34%) patients had reported a history of tobacco smoking, five of them being current smokers at the time of diagnosis. A biliary stent was needed in 46 patients (66%). Out of the patients, one (1%) had previously received adjuvant chemotherapy. Follow-up data were collected until April 2012. Patients' past medical history and the extent of their disease are given in Table I, a-b.
This study protocol was approved by the Hospital District of Southwest Finland.
Results
Gemcitabine was administered to 29 (41%) patients, to 4 (6%) patients in combination with erlotinib and to 13 (19%) patients in the chemoradiotherapy setting. The mean duration of treatment was 6,3 months (0-36 months). Due to deteriorated general condition or patient denial of treatment, 24 (34%) patients did not receive any chemotherapy and were referred to symptomatic care. Smokers, including current and past smokers, had a median survival of 20 months, whereas never-smokers had a median survival of 10 months (p=0.029).
The modes of therapy are listed in Table Ic. Any response (including partial and minor response) was achieved in eight patients (19%). Median overall survival since diagnosis was 11 months for the whole cohort. Median survival of the patients younger than median (68 years) was 19 months and that of the patients older than the median was 8 months (p=0.001). There was no statistically significant difference in median survival between the two genders.
Patients with carcinoma of the pancreas head had the best survival rates, with median survival of 15 months (p=0.001), as compared to carcinoma of the body (6 months), tail (3 months) and other location (4 months). As expected, patients with locally advanced disease at the time of diagnosis had better survival rates (median 14 months) than those with metastatic cancer (median 5 months, p=0.024). The mean survival time of patients with locally advanced or localized disease was 18 months, as compared with that (12 months) of metastatic disease-patients, including lymph node and distant metastasis patients, which was 12 months (p=0.048).
Discussion
The prognosis of pancreatic cancer still remains poor and has not substantially improved during recent years, unlike most other common cancers. In the present study, we retrospectively studied the effect of treatment and patient characteristics on prognosis. Smokers had a better median disease-specific survival than non-smokers. To our knowledge, similar results have not been reported earlier.
Tumours of the pancreatic head are known to be associated with earlier diagnosis than tumours located in the tail of pancreas. More favourable disease outcome is achieved due to obstructive jaundice, which is linked to an earlier diagnosis and thereby better prognosis (15). This probably explains in part our finding. Indeed, smokers more often had tumours located in the pancreatic head than non-smokers, albeit the difference was not statistically significant. The study was retrospective and non-randomized and the patient population was limited, which can explain the differences between smokers and non-smokers. However, maybe due to the limited number of patients, this finding did not reach statistical significance.
We did not find a statistically significant difference in the stage of disease between smokers and non-smokers, in line with previous studies (16). Patients with locally advanced disease had the best survival rates, as expected. The median survival time of cancer of the pancreatic head was 15 months, in parallel albeit somewhat better than in previous studies (2, 17). Not all patients had a histological diagnosis of pancreatic adenocarcinoma. Therefore, some other histological types of cancer and even non-cancerous lesions may have been included in the study. A histological diagnosis is not always achieved even if a biopsy would be taken during laparotomy, with a false-negative rate of 1.6-30% from frozen section biopsies (18-21) 18F-FDG PET/CT may give information to distinguish adenocarcinoma from benign lesions (22) and measuring serum CA19-9 may also be helpful (23). However, repeated biopsies aiming at definitive diagnosis are not often plausible due to rapid disease progression.
The most common mode of treatment was single gemcitabine, which remains a reasonable treatment option even today. Few patients received erlotinib combined to gemcitabine. Of note, no patient received triple chemotherapy, since the results of the FOLFIRINOX trial had not been published at the time of study. In 2010 in our hospital, there were no available clinical trials recruiting patients with pancreatic cancer. Moreover, a substantial part of these patients would not have been eligible in a trial, due to lacking histological diagnosis, comorbidities or patient frailty.
The results of the current study need to be interpreted with caution since the analyses were made retrospectively and since diagnosis was histologically verified only in about one third of the patients. Moreover, smoking status was unknown in about fifth of study population. Also, the small number of patients may influence on the results.
Conclusion
The prognosis of pancreatic cancer still remains poor and it has not substantially improved during the recent years, unlike most other common cancers. In the present study, we retrospectively studied the effect of treatment and patient characteristics on disease outcome in 70 patients treated outside on-going trials in our hospital during a one-year observation period. Interestingly, smokers had a better median disease-specific survival than non-smokers. To our knowledge, similar results have not been previously reported.
a. Patients' medical history.
Acknowledgements
We are thankful to Dr. Outi Hirvonen, MD, PhD, for her valuable insight in palliative cancer care and for her comments about this manuscript.
- Received October 30, 2013.
- Revision received November 13, 2013.
- Accepted November 14, 2013.
- Copyright© 2013 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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