Pancreatic cancer is associated with a poor prognosis, even among patients who undergo a potentially curative resection. Survival estimates for patients with pancreatic cancer who have undergone surgical resection are traditionally reported in the literature as survival from the time of surgery, with 5-year survival ranging from 15% to 25%.2-6
These survival projections may, however, not necessarily be accurate for patients who have survived an initial period of time. That is, patients who have survived a period of time may have a different future prognosis. As such, conditional survival may provide a more useful and clinically relevant estimate of survival probability for patients who have survived a period of time beyond surgery. This may be particularly true for patients with malignancies that have a very poor prognosis, as survival curves estimated from the date of surgery may be overly influenced by the large number of patients who die within the first few years. 16,18
In the current study, we present conditional survival probability estimates for patients with PDAC who underwent curative intent surgery. We found that differences in relative survival probabilities comparing actuarial versus conditional survival estimates were more pronounced based on the additional years already survived by the patient (). Speciflcally, whereas the actuarial survival at 4 years after pancreatic resection was 21 %, the 2-year conditional survival at 2 years—the probability of surviving an additional 2 years given that the patient has already survived 2 years (ie, postoperative year 4)—was 54.9%. These data are important, as the reported conditional survival may provide more clinically relevant prognostic information to patients who have already survived a period of time after surgery for pancreatic cancer.
Several factors have been noted to be associated with survival after surgety for pancreatic cancer. Previous studies have reported that patients with large tumors,5,24
lymph node metastasis,19
or R1 surgical margins5
have a significantly worse long-term prognosis after surgical resection. In fact, in aggregate, patients who have any of tllese associated risk factors have a reported 5-year survival of <10% to 15% as a group. In the current study, we similarly found that tumor size, lymph node status, and margin status were associated with outcome on both univariate and multivariate analyses (). However, perhaps more importantly, we found that certain subsets of patients with these adverse prognostic factors, but who did survive for a period of time, had a higher probability of future survival (-, Bottom
). Although prognostic factors such as tumor size, lymph node, and margin status were important, prognosis based on these factors was misleading, as it was limited to the estimation of initial risk around the time of surgery.16
Conditional survival may be a better alternative to staging systems or isolated static prognostic factors to estimate survival probability over time. Rather than basing prognostic estimations solely on initial risk factors determined at the time of surgery, conditional survival provides a more dynamic assessment of survival probability.16, 25
Exemplified by data in the current study, survival was not only dependent on initial prognostic factors, but was also strongly dependent on time elapsed since surgery. Conditional survival may be particularly germane to inform the prognosis of patients anticipated to have a very poor prognosis, but who have survived a certain amount of time and therefore have beaten the initial odds.17,26,27
For example, 2-year conditional survival estimates for patients with adverse clinicopathological features such as a high lymph node ratio or R1 surgical margin increased the most as a function of the time elapsed since surgery. Specifically, when 2-year conditional survival estimates were stratified by lymph node ratio and margins status, there was a more notable increase in 2-year conditional survival over time when comparing patients with high lymph node ratio or R1 disease versus patients with N0 disease or R0 disease (, , Bottom;
< .05). Data such as these can provide more useful prognostic information that is tailored not only to the clinicopathological characteristics of the tumor, but also to the time a person has already survived after surgery for pancreatic cancer.
Long-term outcomes of patients with a range of malignancies have been examined using conditional survival, although conditional survival for pancreatic Cancer remains ill-defined. Choi et al26
reported conditional survival for patients with ovarian cancer extracted from the SEER dataset. The authors noted that 5-year conditional survival improved over time up to 5 years after diagnosis for ovarian cancer, with the largest gains in conditional survival over time being seen for patients with advanced stage disease, poor grade, and undifferentiated epithelioid histologies. In a separate SEER analysis, Chang et al15
examined conditional survival among colon cancer patients. Chang and colleagues found that conditional survival improved particularly among patients initially predicted to have the worse prognosis. Adjusted 5-year conditional survival improved from 42% to 80% for stage IIIC cancers and 5% to 48% for stage IV cancers. In a larger population-based study using aggregate data from SEER, Merrill et al14
examined 11 different cancers, 1 of which was pancreatic cancer, and reported similar trends. Because pancreas cancer was not a focus of the Merrill et al14
study, interpretation and extrapolation of the data to patients having undergone resection for PDAC was limited. As sllch, we chose to focus exclusively on pancreatic cancer and conditional survival after surgical resection of PDAC. Similar to previous data based on other malignancies,15,26
we noted that conditional survival probablities increased as a function of time already survived (). Specifically, the 2-year conditional survival at 3 years—the probability of surviving to postoperative year 5 given that the patient has already survived 3 years—was 65.7%, compared with a 5-year actuarial survival calculated from the time of surgery of 18.0%. In addition, similar to the findings of Choi et al26
and Chang et al15
we noted that conditional survival improved the most among patients initially predicted to have the worse prognosis (eg, larger tumors, high grade, high lymph node ratio, R1 margin). These data would suggest that standard 5-year survival estimates are not optimal, but also have marginal clinical utility when trying to provide future survival estimates for patients who present with more advanced stages of disease, but who remain alive and continue to be followed months to years later in the clinic.
The current study had several limitations. Due to of the constraints of data collection, we were unable to assess the interaction of the Memorial Sloan Kettering Cancer Center pancreatic survlval nomogram28
and conditional survival. Although we attempted to examine the nomogram, it became evident that some data necessary for tne nomogram calculation were not routinely available in the Johns Hopkins pancreatic database (eg, back pain). However, as our group has previously reported,16
prognostic scoring systems and nomograms frequently suffer from the same shortcomings inherent in an over-reliance on individual prognostic factors. Specifically, nomograms that are based on data exclusively from the time of surgery can be increasingly inaccurate for patients as time elapses.
In conclusion, we demonstrate that survival estimates after surgical resection of PDAC changed as a function of time survived since surgery. Specifically, although the 5-year survival probability was only 18.0% as measured from the time of surgery, the probability of surviving to postoperative year 5 incrementally and dramatically increased as time already survived increased. Factors such as tumor size, as well as nodal and margin status, were associated with worse survival, but relative conditional survival improved the most among those patients who were predicted to have the worse survival at the initial time of surgery. Conditional survival therefore may provide more accurate and useful prognostic information about how prognosis and risk of death change over time for cancer survivors. The data herein presented should help better inform discussions about prognosis among clinicians treating patients who have survived an initial period of time after surgical resection of PDAC.