Predicting 90-day and long-term mortality in octogenarians undergoing radical cystectomy

Radical cystectomy bears a considerable perioperative mortality risk particularly in elderly patients [1‐5]. Robot-assisted surgery has been evaluated as a novel technique in order to decrease adverse outcome in elderly patients [6]. Currently, there is, however, still insufficient evidence to prefer any approach to radical cystectomy [7]. Elderly patients tend to be treated less aggressively although they may benefit from such treatment similarly as their younger counterparts [8, 9]. Since patients with a long remaining life expectancy and a low risk of perioperative mortality are more likely to benefit from radical surgery, identifying those patients could improve disease management. Until now, few tools are available in order to estimate the postoperative and long-term competing mortality risks in octogenarian candidates for radical cystectomy [1‐5, 7‐9].

Tumor-associated parameters (proportion of extravesical extension or positive lymph nodes), 5-year bladder cancer-specific mortality, 90-day mortality and non-bladder cancer (competing) mortality were less favorable in the octogenarian subgroup (Table 1). Octogenarians were more frequently female, less frequently current smokers, had a higher burden of comorbidity and did only rarely receive adjuvant and neoadjuvant chemotherapy (Table 1). Cumulative mortality curves from bladder cancer and from causes other than bladder cancer (competing causes) are shown in Fig. 1. Both types of mortality were higher in octogenarians compared with their younger counterparts (Fig. 1).

Whereas in younger patients the comorbidity measures Charlson score and ASA classification (but not age) were independent predictors of 90-day mortality, in those aged 80 years or older only chronological age was an independent predictor of 90-day mortality (Table 2). Remarkably, despite the range restriction of this variable in patients aged 80 years or older, chronological age became only an independent predictor of 90-day mortality after inclusion of this subgroup (Table 2).

Whereas in younger patients age, Charlson score and ASA classification were independent predictors of long-term competing mortality with p values < 0.001, all three parameters were far apart from the significance level in patients aged 80 years or older (Table 2). In contrast, in younger patients, the ASA classification was of distinct and probably clinically meaningful impact on 90-day and long-term competing mortality after radical cystectomy in younger patients (Tables 2 and 3, Fig. 2). When single conditions were analyzed, in patients younger than 80 years a complex model containing age and six comorbidity-related variables predicted long-term competing mortality whereas in their older counterparts only one variable (history of myocardial infarction) was a significant predictor (Table 3).

This study suggests that extrapolations of 90-day mortality or long-term competing mortality risks of younger patients to octogenarians selected for radical cystectomy should be used with caution. Concerning 90-day mortality, in octogenarians selected for radical cystectomy chronological age could have greater impact than numeric comorbidity. In the full model predicting 90-day mortality in patients aged 80 years or older, the odds ratio of the Charlson score was lower than 1 indicating the loss of prognostic impact of numeric comorbidity (in contrast to findings in other types of cancer surgery [12]), whereas the ASA class with an odds ratio of 3.45 (95% confidence interval 0.66-17.95) sustained some of its prognostic impact visible in younger patients (Table 2). It is conceivable that with a larger sample size this classification might reach the significance level in the elderly subgroup as well.

Comorbidity has been found associated with perioperative death 90-day mortality and 5-year mortality after radical cystectomy [13, 14]. Nomograms have been developed and validated predicting all-cause mortality including variables related to age and comorbidity measured by the Charlson score [15].

In the current study, in patients younger than 80 years, particularly the ASA classification was of distinct and probably clinically meaningful impact on 90-day and long-term competing mortality after radical cystectomy in younger patients (Fig. 2). Whereas the 2017 guidelines of the American Urological Association (AUA) dispensed from detailed recommendations on comorbidity classifications [2], the current guidelines of the European Association of Urology (EAU) discouraged using the ASA classification as comorbidity measure in candidates for radical cystectomy [7]. The huge differences in 90-day and 5-year competing mortality observed after stratification by the ASA classification after previous stratification by the age-adjusted Charlson score [16] (the tool that is recommended by the EAU guidelines for comorbidity assessment [7]) in patients younger than 80 years suggest that the guideline’s discouragement of using the ASA classification should be revised for this subset of patients.

Compared with patients who were 70-79 years of age, octogenarians undergoing radical cystectomy had similar complication rates but increased mortality [17] underlining the need for an identification of vulnerable elderly patients prior to surgery. Furthermore, with a median of 23 months (95% confidence interval 20-27 months), in a recent large multicenter study, the overall survival rate has been reported to be relatively short octogenarians undergoing radical cystectomy [18]. In the current study, with a median of about 30 months, overall survival was something longer (Fig. 1). In a large octogenarian muscle-invasive bladder cancer sample including various types of management, in contrast to the current study comorbidity measured by the Charlson score was an independent predictor of overall mortality with a moderate association with mortality [18]. The inclusion of more impaired patients (only 26% underwent radical cystectomy [18]), an under-recording of less severe conditions in a multicenter cancer registry [18] and a larger sample size may be discussed as possible explanations for these differing findings.

It is conceivable that self-selection by accumulation of minor forms of chronic -diseases during the long life span and the elimination of severe life-threatening forms by premature mortality might diminish the prognostic significance of individual comorbid conditions in octogenarians. In geriatric patients undergoing emergency general surgery, in contrast to age and ASA classification frailty assessed by the Rockwood frailty index predicted postoperative and major complications [19]. Although it would be of interest, few data is available on the role of frailty assessment in elderly candidates for radical cystectomy until now [5].

This study has several limitations. The number of patients aged 80 years or older was limited. Concerning 90-day mortality, the number of events in this subgroup did not allow an analysis with a multitude of variables. Possibly, a multicenter approach including a huge number of octogenarians with well documented clinical data would be promising in order to identify factors other than age and comorbidity that could be associated with outcome in elderly candidates for radical cystectomy [20]. This study was focused on mortality; minor degree complications were not taken into consideration. 90-day mortality in octogenarians undergoing radical cystectomy is higher outside of academic centers [4]. It is possible that different results could be obtained outside an academic setting. Finally, it should be kept in mind that this analysis was based on patients selected for radical cystectomy; the results may not necessarily be extrapolated to a less strictly selected sample of elderly patients.

This data suggest that extrapolations of perioperative mortality or long-term mortality risks of younger patients to octogenarians selected for radical cystectomy should be used with caution. Cystectomy should not be denied in octogenarians by numeric comorbidity. Concerning 90-day mortality, in octogenarians selected for radical cystectomy chronological age could have greater impact than numeric comorbidity.