This is one of the few studies to focus on analysis of independent risk factors for postoperative complications and mortality, employing a substantial sample size with detailed perioperative data and providing a novel nomogram to predict short-term outcomes.
To establish two age groups, the age-specific cut-off point of ≥ 75 years was fitted for the present series, thus providing a non-arbitrary sample stratification. In most previous published studies there is great variability between the age thresholds selected for postoperative outcomes in older patients; they are usually standard cut-off points, not representing inflection points in the series and without medical or biological evidence to support the choice. Some authors also found that age ≥ 75 years could be an optimal cut-off and age has also been stated as a significant risk factor for postoperative complications in colorectal surgery [12]. After analyzing data on physical and psychological health in the older, the Japanese Geriatrics Society proposed that elderly should be defined as those aged 75 years and older [22].
Comparing the two age groups, older patients had a greater number of comorbidities, which were more also severe. Improvements in perioperative multidisciplinary care have made colorectal surgery feasible in the older despite the fact that they frequently present with serious comorbidities [4–6]. Similar to other available studies, in the aged cohort the tumor was more frequently located in the ascending colon, resulting in a higher ratio of right colectomies [6, 16]. As the two subsets differed in their baseline features, PSM was conducted to obtain two homogeneous groups in order to compare postoperative outcomes. Note that all study patients included received the same perioperative bundle of enhanced recovery after surgery protocols, regardless of age.
Similarly to other authors, we found no differences between older and younger patients in postoperative complication rates, including anastomotic leak [6, 13]. These results support that in patients eligible for colorectal resection, a primary anastomosis can be performed safely without excess risk. A recent systematic review and meta-analysis conducted by Hoshino et al. focusing on the outcomes of laparoscopic surgery for CCR in older patients reported slightly higher incidence of postoperative complications in the older, but without differences in anastomotic leak or mortality rates [10].
Our findings revealed that severe postoperative complications were mainly due to worsening of previous comorbidities. Cardiopulmonary complications were more frequent among patients aged ≥ 75 years. Chang et al. also reported pneumonia with respiratory failure as the most common postoperative complication and the leading cause of mortality [17]. In a study of over 1200 CCR patients aged ≥ 85 years undergoing surgical resection, Verweij et al. found high rates of cardiopulmonary complications and excess mortality, particularly in the first year after surgery [11].
The mortality rate for older patients during the postoperative period was 5.3%, in line with outcomes obtained in other studies on octogenarians (2–13%) and nonagenarians (2–20%) [4, 5, 9, 11–16]. Although older patients may present more comorbidities, several studies found no differences in short-term postoperative reoperations or mortality after colorectal surgery [17–19]. Improvements in mortality rates are likely because of advances in perioperative care, safe standardized minimally invasive procedures and better patient selection for surgery. In our experience, although colorectal resection did not involve higher postoperative complication rates in older patients, it did entail higher mortality rates, predominantly in patients with associated comorbidities. Prehabilitation programs could help to optimize preoperative patient status, minimize postoperative risks and improve surgical outcomes. Furthermore, aged patients without concurrent diseases can be successfully treated by curative-intent surgery. Comorbidities may therefore have more impact on postoperative outcomes than age itself.
Age has long been considered among the predominant risk factors for postoperative complications, but essentially due to an increased number of comorbid conditions and worse functional status [4, 11, 12]. Likewise, multivariable analysis revealed that several comorbidities, but not age, were independent predictors of postoperative complications. Moreover, age did not present any association with surgical site infection, anastomotic leak or with reoperation rate. These findings are consistent with those obtained from other large series, where age was not predictive of in-hospital complications or mortality, suggesting that other conditions may impact more significantly in surgical outcomes [8, 12, 14, 19, 20, 23].
Chronic pulmonary disease was an independent risk factor for postoperative adverse events. In other studies, preoperative cardiopulmonary function was determinant in postoperative outcomes [11, 17]. Respiratory physiotherapy is a good measure to incorporate in perioperative care for older patients, given that it could decrease incidence of postoperative pulmonary complications and 30-day mortality [24].
Severe liver disease is a serious comorbidity and was found to be independently associated with adverse postoperative outcomes. Similarly, a recent meta-analysis concluded that pre-existing liver cirrhosis was associated with higher postoperative major complication and mortality rates following CRC surgery [25]. One reason for this could be that abnormal liver metabolism leads to hepatic coagulopathy, lower albumin levels, reduced drug metabolism and weakened immune function, increasing postoperative adverse events.
Laparoscopic surgery is safe in older patients, and moreover, postoperative complications including wound infection, ileus and pneumonia are less frequent than in open surgery [8, 12, 18, 19, 26]. In the present series, laparoscopic approach was found to be independently associated with a lower postoperative complication rate. Similarly, a Dutch population-based study found that compared with open surgery, laparoscopic surgery was independently associated with a lower risk of cardiopulmonary complications and reduced risk of postoperative mortality in elective CCR surgery [21]. Older patients could benefit from laparoscopic surgery despite their limited life expectancy and comorbidities.
Undoubtedly one of the most interesting aspects of our study is the determination of factors influencing postoperative death. In recent years, various prognostic factors for 30-day postoperative mortality have been outlined in older patients, such as age ≥ 85 years, anemia, ASA score IV and palliative cancer surgery [13]. We found that age ≥ 80 years, cerebrovascular disease, severe liver disease and need for postoperative transfusion increased the risk of 30-day mortality. Interestingly, advanced age was not predictive of complications, but was revealed as a predictor for postoperative mortality. A possible explanation could be that although older patients present a similar postoperative complications rate to younger ones, recovery is more hazardous in the former group due to their limited physiological reserve, which could entail a higher risk of mortality. These outcomes are in line with those obtained by Youl et al. in a population-based study in Australia which analyzed postoperative outcomes in 18339 patients aged over 65 years diagnosed with CRC. Among other factors such as advanced tumor stage, open procedure and emergency surgery, age ≥ 75 years was found to be independently related with an increased risk of postoperative death [12]. Other studies have also concluded that comorbidities were the main factors influencing mortality after surgery, but age itself was not [14, 17, 23].
Another aspect frequently associated with worse postoperative complications potentially leading to increased mortality is the need for postoperative transfusion. As expected, therefore, blood transfusion was revealed as a prognostic factor for 30-day complications and mortality, consistent with the results reported in other studies [16]. Similarly, emergent surgery is known to negatively affect surgical outcomes and has been widely proposed as a predictor of postoperative mortality in older patients [4, 11–14, 17]. In the present series, however, we included elective surgery only to diminish confounding factors in the analysis and avoid heterogeneity between groups.
The nomograms constructed in the present study are in line with the few that have previously been published. As in Kiran et al., our model was built with a 70% randomly selected study population and the remaining 30% used to validate it. This ratio was used to avoid overfitting the model. In the multicenter national study conducted by Anaco Study Group, however, the ratio was 60/40 [27, 28]. The models presented similar areas under the curve and share some risk factors. The predictive novel nomograms developed in the present study confirm that prior severe comorbid conditions are the main factors in postoperative short-term outcomes. The nomograms presented herein are useful tools in our setting as they easily provide individualized risk prediction of postoperative complications or mortality, can help clinicians in preoperative evaluation by providing accurate information about postoperative risks, and could facilitate enhanced, tailored multidisciplinary care to minimize complications.
The study included a relatively large sample with non-arbitrary age cut-off points and two homogeneous patient groups obtained through PSM that received the same perioperative care. The prediction model constructed obtained high accuracy and satisfactory internal and external validation, and was presented in the form of a nomogram to facilitate its application by clinicians in outpatient clinics. Nonetheless, this study has some limitations, arising from its observational and retrospective design at a single institution. Data about performance status, frailty, sarcopenia or nutritional status were not recorded, so accurate information about the functional status of the patients was limited.