Age and comorbidities do not affect short-term outcomes after laparoscopic rectal cancer resection in elderly patients. A multi-institutional cohort study in 287 patients

Treatment of locally advanced mid or low rectal cancer is based on neoadjuvant chemoradiation followed by total mesorectal excision (TME) [1]. However, there is no consensus about the optimum surgical management of older patients [2, 3]. Elderly people are an heterogeneous subset of patients. Indeed, while it is considered appropriate to apply the same 'standard of care' to this category of patients, the increased risk of postoperative complications and mortality must be considered in patients with coexisting comorbidities and reduced physiological reserve capacity [4]. In this regard, advanced age should not represent itself a reason for exclusion of patients from radical surgery, but rather the frailty of these patients themselves is to be considered a primary risk factor [2, 3].

Several randomized controlled trials (RCTs) and meta-analyses [5‐9] demonstrated the safety of laparoscopic rectal cancer surgery, better functional recovery and oncological outcomes comparable to open surgery. Despite it is well known that the number of elderly patients is poorly represented in clinical trials, underestimating the 'real-life data' [10‐12], laparoscopic colorectal surgery has significant advantages in short-term outcomes also in the elderly population [13‐15].

However, advanced age and comorbidities increase mortality and occurrence of complications after surgery for rectal cancer [3]. In fact, the preoperative comorbidity rate, which makes the patient vulnerable to postoperative complications, is highest after age 75 [16, 17] and this value may increase in the future because of demographic increase of an aging population and the increase in life expectancy [3].

For this reason, several authors investigated whether a laparoscopic approach in colorectal cancer surgery is as safe and feasible in elderly as in relatively younger patients [18] showing a significative higher overall complication rate in the old people, just like in open surgery [3]. However, focus on laparoscopic rectal resection is limited [19, 20] and these studies are mostly single center without discriminating outcomes between colon and rectal surgery [21‐30], despite rectal surgery is associated with higher complication rate as well as in open surgery [21, 31‐33]. Furthermore, most of the studies concern Eastern populations [19, 21, 23‐28], characterized by lower body mass index (BMI) values and a lower preoperative comorbidity rate than Western population, as well as a limited use of neoadjuvant chemoradiation in locally advanced low rectal cancer, according to Japanese Society for Cancer of the Colon and Rectum Guidelines for the treatment of colorectal cancer [34]. Finally, the chronological cut-off is often 70 years, although it is now widely accepted that for the definition of elderly patient it should be of 75 years [35].

Because of the paucity of data concerning rectal cancer treatment and heterogeneous studies on the issue, the aim of this study is to assess the safety of laparoscopic approach for the treatment of rectal cancer in elderly patients and the impact of age on postoperative clinical outcomes, by comparing the characteristics and results of a retrospective analysis with those of a relatively younger patient group. Additionally, the study aim to evaluate age and comorbidities as potential independent risk factor for postoperative complications.

The rate of surgical resections for rectal cancer has significantly decreased over the years in patients ≥ 75 years of age [43]. This is partly due to higher comorbidity prevalence of patients [4], but also to the development of conservative treatment options showing remarkable results [44, 45], although there are still some controversial aspects and a limited application of these alternative treatments to current clinical practice [46, 47]. Surgery still remains the main 'cornerstone' for the treatment of rectal cancer, demonstrating a progressive implementation of minimally invasive techniques with acceptable oncological and functional outcomes [48]. In this setting, laparoscopy has proven to be safe, advantageous and an effective alternative to open surgery even in elderly patients with colorectal cancer [49], as well as for benign diseases [50]. Thus, the next step was to assess whether there was a difference in short-term outcomes after laparoscopic surgery for colorectal cancer between the elderly and non-elderly population. A recent meta-analysis finds a higher overall complication rate in elderly patients aged ≥ 75 years undergoing laparoscopic colorectal resections (p < 0.01) [18] likewise of the open approach [3]. However, the review includes both colonic and rectal laparoscopic resections. Since few studies exclusively considered rectal surgery or separately reported data after laparoscopic rectal cancer surgery in the elderly patients, [19, 20, 51, 52], the aim of the present study was to assess whether a more vulnerable population, consisting of older people, can benefit from a minimally invasive surgical approach for the treatment of rectal cancer in the same way as relatively younger people by evaluating age groups and individual or overall comorbidities as possible indipendent risk factor.

In this study, although older patients have both the ASA score and the prevalence of cardiovascular disease significantly higher than the non-elderly patients, the postoperative complication rates and the number of patients with complications between the over-75 group and the under-75 are comparable. Also, there were no significant differences in length of hospital stay and mortality rate.

The leakage rate after anterior rectal resection ranges from 3 to 23% [53]. In the present study, the incidence of anastomotic leakage is higher in the cohort of patients aged < 75 years, although it does not reach a statistically significant difference (15.2% vs. 6.5%; p = 0.07). This discrepancy can be attributed to various intraoperative risk factors such as long operative time, the number of stapler firings and anastomotic level that are associated with increased risk of leakage [54, 55], but which were not taken into account in the analysis. Treatment was mainly carried out by relaparoscopy given the great experience of the centers [56].

Finally, the results of multivariate regression analysis show that only male gender and low-mid rectal tumor localization are independent risk factors related to postoperative morbidity, whereas age and associated comorbidities did not have an impact on complications. These findings suggest that the laparoscopic approach for rectal cancer surgery is safe and appropriate even for patients aged ≥ 75 years, by demonstrating a rate of adverse events after surgery similar to that of patients under 75.

The results of the present study is consistent with the few previous reports that compared the safety and feasibility of laparoscopic rectal resection of the elderly with younger patients and they may be useful in clinical practice if interpreted wisely to mitigate the risk of conversion [57]. From Table 5, only one study exclusively focuses on rectal cancer surgery [19], two of them reported and compared preoperative patients’ data [19, 20] and no logistic regression analysis was performed in any study to identify predictors of complications. Therefore, only in the present case series, the age of patients divided into groups and the impact of individual and overall preoperative comorbidity were systematically excluded as possible independent risk factors of postoperative complications, assuming that laparoscopic surgery should be a valid choice for the elderly patient with rectal cancer because of an overall complication rate comparable to rate non-elderly patients, unlike open surgery [3] or as reported elsewhere [18].

It has been demnostrated that laparoscopy and robotic surgery have similar effectiveness in oncologic outcomes, but robotic surgery may have lower conversion rates compared to laparoscopy especially in patients with high BMI, lower lesions and after neodjuvant [58]. However, it also true that laparoscopic rectal cancer resection in selected and fit patients and in high-volume centers with laparoscopic expertise can achieve safe oncological outcomes and margins with sphincter-sparing dissection, even in ultralow rectal cancers and without needing of robotic surgery or transanal TME (TaTME) [59]. In this setting, robotic TaTME seems a promising apporach to improve the outcomes and feasibility of low rectal cancers resections but this technique, although recently described [60] is still considered too preliminary by some authors and can not be recommended as yet [61].

This study has several limitations. The absence of a satisfactory matching process limits the risk of bias regarding its retrospective design as well as the limited number of patients over 75, although data comes from multiple centers. In addition, the long-term oncological outcomes and data relating to the Enhanced Recovery After Surgery protocol (ERAS) are not included. Furthermore, the choice of a laparoscopic approach rather than others to performe rectal resection was at the discretion of each surgical team increasing the risk of selection bias. However, the analysis of data collected from high-volume laparoscopic colorectal surgery centers suggests that patients over 75 years old benefit of a laparoscopic approach as well as younger patients despite advanced age and previous comorbidities.

These findings may depend on the fact that the most problematic expression of population aging would not be the age ot the comorbidities, but the clinical condition of frailty, which is defined as “a state of increased vulnerability to poor resolution of homoeostasis after a stressor event, which increases the risk of adverse outcomes, as a consequence of cumulative decline in many physiological systems during a lifetime” [62]. However, it is believed that this cannot significantly compromise the results of the present study. In fact, a systematic review of the literature shows that the prevalence of frailty increases with age [63] and according to some authors the concept of fragility is closely related to comorbidity and frequently overlaps with it [64]. In addition, there is no clear consensus on the definition to date. On the one hand, it is considered only a phenotype of fragility exclusively linked to the physical condition; on the other, it is considered more appropriate to extend its definition to include social and psychological aspects [63]. Finally, several screening methods have been developed to predict the degree of frailty in elderly patients with cancer, but none have demonstrated sufficient discriminatory power, stating that a comprehensive geriatric assessment is the most valid modality. [65]. However, a multidisciplinary holistic assessment of the elderly patient in the perioperative period remains desirable.

Despite higher incidence of cardiovascular disease and a higher anesthesiologic risk, short-term postoperative outcomes in patients ≥ 75 years of age are similar to those of younger patients after laparoscopic surgery for rectal cancer. Advanced age and preoperative evaluated comorbidities are not related to an increased risk of postoperative morbidity, unlike open surgery. Therefore they should not represent a limitation to laparoscopic rectal resection.