The present study investigates the question of whether laparoscopy and laparotomy are equally suitable in all age groups. The analyses on 10,745 patients from a German cancer registry grid showed nonsignificant advantages for laparoscopically treated patients concerning the 30-day postoperative mortality with similar results in all age groups. In terms of 5-year overall survival, the superiority of laparoscopy remains significant in all age-stratified subgroups even after adjustment for relevant covariables. The minimally invasive approach is also followed by lower recurrence rates. Concerning 5-year recurrence-free survival, younger patients seem to benefit more from laparoscopy.
These results give valuable insight into the daily clinical practice of rectal cancer surgery, since data comparing long-term results after laparoscopic vs. open approaches are scarce. It is only 3 years ago, that one of the first high-quality randomized controlled trials (RCTs) on the topic, the international COLOR II trial, was published . These authors demonstrated the general oncologic safety of the minimally invasive approach. The validity of these positive results in daily clinical practice was confirmed by analyzing a representative cohort of approximately 1500 patients from southern Germany . However, no two patients are exactly alike, and only individualized treatment will result in optimal outcomes, hence the need for more detailed analyses.
When selecting the appropriate therapeutic pathway to treat cancer, many aspects must be considered. Age is inevitably one of these aspects. Several studies have shown that there is a strong association between age and the prevalence of comorbidities [26, 27]. Therefore, there is a consensus that studies comparing treatment options such as different surgical approaches must regard age as a potential confounder, at least if the age distribution differs between treatment groups.
In most observational studies on the topic, laparoscopically treated patients have tended to be younger. For example, Nussbaum et al. used a large cancer registry from the USA and examined approximately 19,000 patients with low anterior rectum resection due to carcinoma . Patients receiving minimally invasive surgery were significantly younger by 1 year. In 2015, Yeo et al. performed a large multicenter trial and found laparoscopic surgery patients to be, on average, 2.5 years younger . In the publication of Draeger et al., laparoscopy patients were younger by 2.9 years on average, with age groups significantly differently distributed among the comparison groups (p < 0.001) . Kolfschoten et al. also identified lower age as a relevant predictor for the laparoscopic approach . Even in the randomized COLOR II trial, an age difference of 1 year between groups could be observed, while in this case, laparoscopic patients had the higher mean age, with 66.8 years . Age obviously plays an important role in the selection of surgical approach.
This raises the question of whether laparoscopy and laparotomy are equally suitable in all age groups. A large study population is crucial for representative and statistically stable results at the subgroup level. Unfortunately, the problem of enrolling a sufficiently large number of participants is a common issue in RCTs. COLOR II, for instance, although currently the largest clinical trial on rectal cancer surgery, included only 1044 patients . More substantial caseloads are reached in some registry-based studies, such as that of Nussbaum et al. . However, most of these investigations suffer from a different limitation: in the absence of data on long-term survival, analyses have to be restricted to perioperative outcomes. To the best of our knowledge, the present study is the first with both a substantial caseload and true long-term follow-up. The age-stratified comparison of laparoscopic and open surgery for colorectal cancer resection performed herein permits assessment of potential effect modification of survival outcomes for the first time.
Some limitations must be considered when interpreting the results presented in this study. Unfortunately, information on nononcologic comorbidities is lacking, since there is no consensus between the participating cancer registries on the issue and, therefore, systematic documentation of American Society of Anesthesiologists (ASA) or a comorbidity score does not take place. However, there is evidence that stratifying by age, as it was done in this study, may partly account for this shortage: older patients tend to suffer from more potentially life-threatening illnesses than younger patients . According to a survey by the Dutch cancer registry on colorectal cancer patients, there is a significant association between age and the number of comorbidities . Notwithstanding, a future systematic documentation of ASA or a different comorbidity score is desirable to enable more accurate risk adjustment.
As stated above, this survey aims to paint a holistic picture of national rectal cancer care. Therefore, many regional cancer registries were encouraged to provide their data. However, some of these institutions are better established than others, leading to a somewhat inhomogeneous data quality level. If information gaps could not be filled, patients had to be excluded to match mandatory statistical standards. Therefore, a sensitivity analysis was conducted and could show that the necessary exclusion process only introduced a small amount of bias into the analysis of long-term survival, while results on short-term survival were not influenced significantly at all. Thus, all presented findings can be regarded as stable.
Concerning short-term outcomes, laparoscopic surgery patients in this study had a lower postoperative mortality rate in all age groups. However, the effect size was only moderate and the significance level was not reached in any age group. Extensive literature research revealed that Landi et al. also analyzed death within 30 days after surgery and found a significantly lower mortality rate in the laparoscopic than the open surgery group for patients under 80 years (0 vs. 4.6%, p = 0.049) . A possible reason for the advantage of the minimally invasive surgical approach could be the lower postoperative complication rate. For example, Kolfschoten et al. and Mroczkowski et al. observed a higher number of complications after the conventional approach [6, 30]. McKay et al. divided their collective into patients under and over 70 years and analyzed the postoperative complication rate. In both age groups, more complications occurred after open surgery. Additionally, the complication rate was higher among patients aged over 70 years, both in the open and in the laparoscopic group . Taking all these studies into account, laparoscopy indeed seems to be the superior surgical approach in terms of short-term outcomes, but age is not an effect modifier.
A significant advantage of laparoscopy could again be observed for overall survival in all age groups 5 years after surgery. Regarding recurrence-free survival, rates were higher in the laparoscopic group, although the significance level was no longer reached in the oldest group. Taking a closer look at the actual effect sizes after adjustment for confounders, an age-dependent gradient can be seen: With 0.703, the HR for laparoscopy is lowest in the youngest age group, grows to 0.787 in patients between 60 and 69 years, and is highest among septuagenarians (HR = 0.923). In the long term, young people obviously benefit most from minimally invasive surgery, while survival and recurrence patterns in older patients seem to depend less on the surgical approach. Future research is indispensable to further investigate the reasons for this observation.
All results of this study are based on 10,745 patients from 30 regional cancer registries covering approximately one quarter of the German population and can be regarded as representative. Even considering all limitations, the presented findings are statistically stable over all investigated age groups. Moreover, the application of multivariable analyses and relative survival models generated adjusted results going beyond mere observation. These can be used for direct comparison with patient samples from other regions. Thus, future research on this topic shall be encouraged.