Open Access

Comparison of Selected Older and Younger Patients Regarding Optimal Surgical Treatment of Colorectal Cancer: A Prospective Cohort Study

AGGELAKOPOULOU CHRYSA 1
PERIVOLIOTIS KONSTANTINOS 1
STERGIANNIS PANTELIS 2
INTAS GEORGE 3
MOUZAKIS GEORGE 1
  &  
TEPETES KONSTANTINOS 1

1Department of Surgery, University Hospital of Larissa, Larissa, Greece

2Department of Oncology, General Hospital “Agioi Anargyroi”, Athens, Greece

3General Hospital of Nikaia “Agios Panteleimon”, Athens, Greece

Cancer Diagnosis & Prognosis Jul-Aug; 3(4): 504-513 DOI: 10.21873/cdp.10247
Received 30 April 2023 | Revised 25 May 2024 | Accepted 25 May 2023
Corresponding author
Konstantinos Perivoliotis, Department of Surgery, University Hospital of Larissa, Mezourlo, 41110, Larissa, Greece. Tel: +30 2413501000, email: kperi19@gmail.com

Abstract

Background/Aim: Current evidence regarding the optimal management of older colorectal cancer patients, is conflicting. Functional deficits impact long-term survival prognosis, while frailty often results to optimal treatment postponement. Thus, the characteristics of this subgroup combined with treatment deviations further perplex optimal oncological management. The study aim was to compare survival and optimal surgery rates between older and younger colorectal cancer patients. Patients and Methods: This study was designed as a prospective cohort. All adult (³18 years) colorectal cancer patients operated, during the 2016-2020 period, in the Department of Surgery, University Hospital of Larissa, were considered as eligible. The primary endpoint of the study was the difference in terms of the overall survival between older (>70 year) and younger (<70 years) colorectal cancer patients. Results: Overall, 166 patients (60 younger and 106 older) were enrolled. Although the older subgroup displayed a higher rate (p=0.007) of ASA II and ASA III patients, mean CCI scores were comparable (p=0.384). The two subgroups were similar in terms of performed operations (p=0.140). No delay in surgery was noted. Most operations were performed using an open approach (open: 57.8% vs. laparoscopic: 42.2%), under an elective status (elective: 91% vs. emergency: 1.8%). There was no difference in terms of overall complications rate (p=0.859). Overall survival was similar (p=0.227) between the older and younger subgroups (25.68 vs. 28.48 months). Conclusion: Older operated patients did not differ from their younger counterparts with regard to their overall survival. Due to several study limitations, further trials are required to confirm these findings.
Keywords: cancer, comorbidity, older, ASA, Charlson, colorectal

Colorectal cancer is among the most common gastrointestinal malignancies. Current epidemiologic studies confirm the stabilization or the decrease of standardized incidence and mortality rates in high income countries, while a considerable increase in early-onset colorectal cancer is, also, noted (1,2). Furthermore, it is estimated that, over 300,000 new cases per year are diagnosed in Europe alone, while the pooled 5-year survival rate is approximately 65% (2-5). Additionally, almost 60% of these patients are older than 70 years old, with considerable comorbidities and physical impairments (3-5).

However, older patients (>65 years of age) are a very heterogeneous group, with notable deviations in terms of fitness and frailty (6-11). More specifically, the presence of underlying functional and mobility deficits combined with suboptimal nutritional status and ageism impact the prognosis of such patients (12-14). Therefore, a formal geriatric assessment with validated tools, generally provides more accurate classification, compared to a simple age cut-off point (12-15). These patients have been, traditionally, undertreated, receiving in many cases suboptimal oncological operations.

Additionally, due to the accompanying comorbidities and reduced survival expectancy, these patients are systematically excluded from clinical trials (6-11). Moreover, besides strict inclusion criteria, the lack of family support and the surgeons’ prejudice for increased risk of morbidity, led to a systematic under-representation of these patients in colorectal cancer studies (13,14). However, these disparities are quite problematic since older patients have the highest rates of malignancies, alongside major socioeconomic obstacles (13,14).

Surgical resection alongside perioperative therapy is the gold standard approach in colorectal cancer (7,9-11,16-18). However, radical resections are associated with a considerable morbidity and mortality burden. Thus, especially in older patients, frailty, and physical reserves limitations, often lead to the postponement or deviations from the optimal treatment (7,9-11,16-18).

Current evidence regarding the optimal management of older colorectal cancer patients, is still a matter of controversy (19-24). More specifically, initial cohorts suggested that older patients display a higher risk of perioperative complications, whereas recent studies reported that optimal oncological resections can be safely performed in this age subgroup (19-24). The significance of these is that optimal management of colorectal cancer in older patients has a direct impact on the oncological outcomes, including survival and recurrence.

Therefore, the aim of this prospective study was to compare the differences between older and younger colorectal cancer patients in terms of survival and the delivery of optimal surgical treatment.

Patients and Methods

Study endpoints. The primary endpoint of the study was comparison of the older (>70 year) and younger (<70 years) patient subgroups in terms of overall survival (OS) (25). Secondary endpoints included optimal surgery rates and OS comparisons based on optimal treatment and the interaction of optimal and age subgroups.

Optimal treatment was defined as the operation that allowed complete oncological clearance based on tumor location and stage. More specifically, for right and left colon cancer that was translated to colectomy adhering to the CME/CVL principles, with adequate resection margins. Similarly optimal treatment for rectal cancer was considered resection based on the TME principles followed by anastomosis when applicable. Any deviation from these principles, or any salvage operation (e.g., bypass procedures or defunctioning stomas) was considered as suboptimal treatment.

Study design. This prospective observational study was conducted at the Department of Surgery, University Hospital of Larissa, Larissa, Greece. All patients submitted to colorectal cancer surgery during the January of 2016 -April of 2020 period, were included in this study. Prior to patient inclusion, the appropriate local ethics committee approval and informed consent were received. The present study results are reported based on the STROBE guidelines (26).

Eligibility criteria. Eligible patients were considered all consecutive adult patients (³18 years), diagnosed with colorectal cancer and operated in our Department during the aforementioned period. The following exclusion criteria were considered: 1) non-adult patients, 2) refusal to participate and provide a signed informed consent, 3) operations performed outside the investigation period, 4) recurrent tumors and 5) patients not submitted or unfit for surgical treatment.

Treatment. All operations were performed by a group of 4 consultant surgeons. All surgeons had previous experience in open and laparoscopic colorectal surgery and had completed the respective learning curves. A standardized surgical technique was used in all cases. Dissection was performed with an energy source.

Data collection. Data regarding demographics [age, sex, American Society of Anesthesiologists -ASA score, Eastern Cooperative Oncology Group (ECOG) status, comorbidities, and Charlson Comorbidities Index (CCI)], tumor characteristics (TNM classification and tumor location) and operative and perioperative treatment outcomes (resection type, surgery delay, operation status, surgical approach, additional resections, and perioperative therapy) were recorded. Moreover, all perioperative adverse events, readmission and reoperation rates were recorded. Patient characteristics were retrieved from institutional databases, whereas morbidity and survival data were recorded during follow-up. The latter included scheduled outpatient visits and telephonic call evaluations.

Statistical analysis. Prior to statistical analyses, a Kolmogorov-Smirnoff normality test was performed. Chi-square test was applied in categorical variables, whereas a t-test and a Mann-Whitney U-test was used for normal and non-normal continuous outcomes, respectively. Pearson’s correlation coefficient was also introduced for association analyses. Survival analysis was based on the Kaplan-Meier curves and the Log-Rank test. Continuous data were provided in the form of Mean (Standard Deviation) or Median (Interquartile Range) on the basis of normality results, while categorical variables were reported as N (Percentage). Significance was considered at the level of P<0.05. Statistical analyses were completed by SPSS v.21 software.

Ethics approval. This study was performed in line with the principles of the Declaration of Helsinki.

Informed consent. Informed consent was obtained from all individual participants included in the study. Patients signed informed consent regarding publishing their data and photographs.

Results

Patient characteristics. Overall, 166 patients were enrolled in the study (Table I). More specifically, 60 (36.1%) younger and 106 (63.9%) older patients were submitted to colorectal cancer surgery. Mean age in the former and the latter group was 62.27 and 77.8 years, respectively. There was no difference in terms of mean weight and sex allocation. Even though the older subgroup displayed a higher rate (p=0.007) of ASA II (56.7% vs. 61.3%) and ASA III (0% vs. 11.3%) patients, mean CCI scores were comparable (p=0.384) between the two groups. Older patients were not associated with increased rates of high ECOG (p=0.384) status. Similarly, besides coronary heart disease (1.7% vs. 12.3%), overall and specific comorbidities rates did not differ among the older and younger patients.

Treatment characteristics. In Table II, a summary of the TNM classification characteristics is displayed. In total, 35 cecum/ascending colon, 14 transverse colon, 60 descending colon and 57 rectal were introduced in this study. Moreover, 55 right colectomies, 2 extended right colectomies, 18 left colectomies, 24 sigmoidectomies, 40 low anterior resections, 3 abdominoperineal resections, 6 transverse colostomies, 8 loop ileostomies, 6 Hartmann’s procedures, 3 subtotal colectomies and 1 bypass were performed (Table III). There was no significant difference between the two subgroups in terms of the performed operations (p=0.140). Furthermore, there was no delay in surgery. Most of the operations were performed in an open approach (57.8%), under an elective status (91%). Additional resections were implemented in 2.4% of total cases. Additionally, a homogeneous allocation, in terms of neoadjuvant and adjuvant schemes (p=0.138), was recorded. A R0 resection was achieved in 95.5% of cases. Median follow-up for the pooled patient sample was 24 months.

Postoperative outcomes. There was no difference between older and younger patients (18.9% vs. 20%) in terms of overall complications rate (p=0.859). The pooled anastomotic leakage rate was 4.8%. Comparable readmission (p=0.67), reoperation (p=0.260) and ICU (p=0.855) admission rates were also noted. There was no difference in any other perioperative adverse event.

Primary endpoint. Regarding the primary outcome, mean survival was 26.69 months. There was no difference (28.48 vs. 25.68 months) between the two study arms (p=0.227). Similar were the results from the survival analysis function (Figure 1, Log-Rank test p=0.224).

Secondary endpoints. The optimal surgery rate was similar (p=0.074) between the younger and older subgroups (80% vs. 67%). There was no difference in terms of diagnosis to admission (p=0.973), admission to operation (p=0.893) and diagnosis to operation (p=0.992) time.

Finally, there was no survival discrepancy between the optimal and the suboptimal surgery groups (Figure 2, Log-Rank test p=0.674). Subgroup analyses (older & suboptimal, older & optimal, younger & suboptimal, younger & optimal) did not highlight any statistically significant survival difference (Figure 3, Log-Rank test p=0.467).

Discussion

Colorectal cancer is among the most frequently encountered malignancies. Almost 760,000 males and 614,000 females are diagnosed with colorectal cancer every year, worldwide (19). This corresponds to almost 5% of the total population developing a colorectal tumor at least once in their life span (19).

Recent innovations in medicine have allowed an increase in the life expectancy of the Western countries’ population. It is estimated that the average life span of the developed nations ranges from 78.6 to 84.2 years, with an increasing trend (27). However, the definition of the term ‘older’ is still unclear (Geriatr Gerontol Int 6(3) (2006)">28). Conventionally, patients aged over 65 years old were regarded as older (Geriatr Gerontol Int 6(3) (2006)">28). However, in current literature, definitions up to 75 years old were reported (Geriatr Gerontol Int 6(3) (2006)">28-31). Furthermore, recent definition proposals incorporated the loss of functional independence and frailty as an additional differentiation characteristic of elderly (Geriatr Gerontol Int 6(3) (2006)">28-31). Based on previous cohorts, we defined the two subgroups of our study by the 70 years age key-point.

Overall, cancer is considered as a disease of the older patients; in terms of colorectal cancer, a parallel tendency of the prevalence rate, with the increasing age is noted (22). For instance, patients aged 60-64 years have, almost, the half incidence of colorectal malignancies, compared to the respective 80-84 years old cases. Based on these and alongside the escalation of the pooled incidence, it becomes apparent that the total number of older patients with colorectal cancer is expected to increase (22).

A multimodal approach is the current gold standard treatment for colorectal cancer (32). Radical resection combined with neo-adjuvant and adjuvant modalities allowed prolongation of the overall and disease-free survival, while in parallel minimizing the local and distant recurrence rates (32,33). However, the former, still, remains a controversial issue for older patients, since many cohorts confirmed that age is an independent prognostic factor of postoperative morbidity and mortality (21). More specifically, the increasing burden of systematic comorbidities reduces the physiological reserves, thus jeopardizing the final, postoperative outcome.

Several clinical studies have compared the two age groups in terms of perioperative endpoints. Fiscon et al. (34) reported a 24% complications rate in older patients, compared to the respective 8% of their younger counterparts. In the study of Bottino et al. (23), although no difference in overall complication rate was noted, older patients were associated with an increased risk for cardiopulmonary adverse events. In our study pooled complications rate was comparable between older and younger patients. Specific postoperative adverse event analyses showed similar results. These findings are in contrast with the results of a recent meta-analysis, where a significant difference in terms of pooled morbidity was found (20). However, Hoshino et al. (20) noted that despite statistical significance, the magnitude of difference was quite small. Possible confounders that may affect these results could be the lack of randomization, the absence of reporting standardization and the inherent heterogeneity of patient, tumor, and operation characteristics (20).

During the previous decades an age over 80 years was considered as an exclusion criterium for radical oncological resection (22). Therefore, in these patients, a palliative approach, such as diverting stoma or bypass, was often introduced. However, the advances in preoperative rehabilitation, optimization of comorbidities, intraoperative monitoring and surgical innovations allowed the safe implementation of more extensive resections (22). In our trial, oncological resections were the primarily surgical approach in both groups. Moreover, palliative procedures were performed in a comparable rate, while in parallel we confirmed that the delivery of optimal treatment was not affected by the age subgroup.

The benefits of minimal invasive colorectal resections are well established. The minimization of surgical trauma further reduces the perioperative inflammatory cascade (35). Improved cosmesis, reduced postoperative pain, enhanced mobilization and bowel function recovery are amongst the several advantages of laparoscopic colectomies (36). Nonetheless, the safety of laparoscopic colorectal resections in octogenarians is, still, a matter of controversy. The hemodynamic changes induced by the pneumoperitoneum combined with the prolonged operative times and the extreme intraoperative positions challenge the already reduced reserves of patients with cardiopulmonary comorbidities (20,21,37). However, in a clinical study by Akiyoshi et al. (37), an improved morbidity profile was suggested when a minimal invasive approach was applied in older patients. In our study 42.2% of the pooled resections were performed laparoscopically. There was no notable difference between the two groups in terms of morbidity.

Assessment of survival endpoints is a pivotal part of colorectal cancer trials. Overall and cancer-specific survival rates directly reflect the oncological efficacy of the investigated interventions. Interestingly, we could not verify any survival difference between older and younger colorectal cancer patients. Moreover, these results did not differentiate when the optimal surgery covariate was introduced. According to a systematic review by Colorectal Cancer Collaborative Group, older patients displayed a reduced overall survival, with minimal differences in cancer specific survival compared to their younger counterparts (38). Similarly, Golfinopoulos et al. reported comparable survival benefits of adjuvant and palliative chemotherapy between older and younger colorectal cancer cases (39). Moreover, colorectal cancer surgery outcomes are multifactorial and can be affected by multiple factors besides age, including stage, comorbidities, and chemotherapy scheme (38). For example, in stage IV patients, surgery has a limited effect in the overall prognosis. In our study, a relatively small cohort was assessed with a significant heterogeneity in terms of cancer staging, thus limiting the ability to safely extrapolate these results.

Our study showed that applying a suboptimal treatment in older colorectal cancer patients did not significantly affect survival outcomes. More specifically, median survival for older patients with suboptimal surgical treatment was 22.8 months compared to 25 months in the optimal arm. The best survival rate was identified in the younger and optimal subgroup (28 months). Despite these differences statistical significance was not confirmed. A possible explanation could be the previously mentioned study limitations. Current literature suggests that perioperative optimization and technological advancements allow the performance of optimal oncological resections in octogenerians with acceptable results (40). Multiple trials confirmed a survival benefit of optimal surgical treatment in older patients without documenting any safety hazard (41,42).

Despite the therapeutic potential in colorectal cancer, surgical resection represents a major physiological trauma that derails the homeostasis of a frail patient (43,44). More specifically, the extent of perioperative risk is directly correlated with the preoperative functional reserves of the patient (43,44). In octogenerians, cardiac, pulmonary, and metabolic comorbidities combined with malnutrition and other psychological disorders inhibit an early and uneventful postoperative recovery (43,44). Therefore, the introduction of multimodal pre-habilitation programs was considered as a means of improving cardiorespiratory fitness in older patients (43,44). Although these preemptive interventions typically consist of nutritional support combined with aerobic exercise and strength training, the exact protocol and duration is, still debated (43,44). Similarly, current evidence regarding the efficacy of such interventions is not, yet, conclusive (43-45). In our cohort no pre-habilitation protocol was applied.

Preoperative screening of biological vulnerability aims in the early identification of reduced reserve and stressor resistance in geriatric patients (46-48). During the previous years, multiple frailty assessment instruments were described (46-48). These were categorized in frailty phenotype instruments and frailty index tools; the former predominantly evaluated motor and activity scores, while the latter assessed comorbidities, social factors, cognition, and psychological disorders (46-48). Subsequently, a great discrepancy is noted among the results of these tools, and a gold standard frailty index is, yet, not established. Besides the plethora in assessment tools, the absence of hard evidence and implementation guidance, further prevents the systematic frailty evaluation of older patients (46-48). It is estimated that a frailty assessment algorithm is rarely introduced in daily clinical practice and that only in selected cases (49). In our study, a formal geriatric assessment was not performed. Patients were categorized based on a pre-defined age cut-off, while a validated comorbidity tool was also used.

Several limitations must be considered with regard to the present study. First, the study was designed as a prospective trial, thus increasing the risk of bias due to absence of masking and randomization algorithms. Furthermore, the relatively small sample size may have negatively affected the validity of our findings. Additionally, the differences in terms of tumor and operative characteristics were another noteworthy source of bias. Finally, divergences in the perioperative schemes, further, contribute to the overall heterogeneity.

Conclusion

Our cohort study highlighted that operated older colorectal cancer patients had similar survival rates with their younger counterparts. Furthermore, the two arms were comparable regarding overall morbidity and optimal surgery rates. Finally, subgroup analysis in terms of patient age and optimal surgical approach did not reveal any survival difference. However, due to several study limitations, further trials, of a higher methodological quality and of a larger sample are required to confirm these findings.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflicts of Interest

The Authors declare that they have no conflicts of interest.

Authors’ Contributions

Conception and design of the study: Tepetes, Aggelakopoulou; Acquisition of data: Aggelakopoulou, Mouzakis; Drafting the article: Perivoliotis, Aggelakopoulou; Critical revision: Stergiannis, Intas. Final approval: Tepetes.

References

1 Patel SG Karlitz JJ Yen T Lieu CH & Boland CR The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol. 7 262 - 274 2022. DOI: 10.1016/S2468-1253(21)00426-X
2 GBD 2019 Colorectal Cancer Collaborators Global, regional, and national burden of colorectal cancer and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Gastroenterol Hepatol. 7 627 - 647 2022. DOI: 10.1016/S2468-1253(22)00044-9
3 Edwards BK Noone A-M Mariotto AB Simard EP Boscoe FP Henley SJ Jemal A Cho H Anderson RN Kohler BA Eheman CR & Ward EM Annual Report to the Nation on the status of cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among persons with lung, colorectal, breast, or prostate cancer. Cancer. 120 1290 - 314 2014. DOI: 10.1002/cncr.28509
4 van Leersum NJ Janssen-Heijnen MLG Wouters MWJM Rutten HJT Coebergh JW Tollenaar RAEM & Lemmens VEPP Increasing prevalence of comorbidity in patients with colorectal cancer in the South of the Netherlands 1995-2010. Int J Cancer. 132 2157 - 2163 2013. DOI: 10.1002/ijc.27871
5 Sarfati D Tan L Blakely T & Pearce N Comorbidity among patients with colon cancer in New Zealand. N Z Med J. 124 76 - 88 2011.
6 Søgaard M Thomsen RW Bossen KS Sørensen HT & Nørgaard M The impact of comorbidity on cancer survival: a review. Clin Epidemiol. 5 3 - 29 2013. DOI: 10.2147/CLEP.S47150
7 Cashman J Wright J & Ring A The treatment of co-morbidities in older patients with metastatic cancer. Support Care Cancer. 18 651 - 5 2010. DOI: 10.1007/s00520-010-0813-1
8 Sawhney R Sehl M & Naeim A Physiologic aspects of aging: impact on cancer management and decision making, part I. Cancer J. 11 449 - 460 2005. DOI: 10.1097/00130404-200511000-00004
9 Handforth C Clegg A Young C Simpkins S Seymour M Selby P & Young J The prevalence and outcomes of frailty in older cancer patients: a systematic review. Ann Oncol. 26(6) 1091 - 1101 2021. DOI: 10.1093/annonc/mdu540
10 Shamliyan T Talley K Ramakrishnan R & Kane R Association of frailty with survival: A systematic literature review. Ageing Res Rev. 12(2) 719 - 736 2018. DOI: 10.1016/j.arr.2012.03.001
11 Schiphorst A Pronk A Borel Rinkes I & Hamaker M Representation of the elderly in trials of laparoscopic surgery for colorectal cancer. Colorectal Dis. 16(12) 976 - 983 2014. DOI: 10.1111/CODI.12806
12 Wong Y Hang J Francis-Coad J & Hill A Using comprehensive geriatric assessment for older adults undertaking a facility-based transition care program to evaluate functional outcomes: a feasibility study. BMC Geriatrics. 22(1) 598 2022. DOI: 10.1186/S12877-022-03255-5
13 Marum R Underrepresentation of the elderly in clinical trials, time for action. Br J Clin Pharmacol. 86(10) 2014 - 2016 2020. DOI: 10.1111/BCP.14539
14 Herrera AP Snipes SA King DW Torres-Vigil I Goldberg DS & Weinberg AD Disparate inclusion of older adults in clinical trials: priorities and opportunities for policy and practice change. Am J Public Health. 100 S105 2010. DOI: 10.2105/AJPH.2009.162982
15 Audisio R Ramesh H Longo W Zbar A & Pope D Preoperative assessment of surgical risk in oncogeriatric patients. Oncologist. 10(4) 262 - 268 2005. DOI: 10.1634/THEONCOLOGIST.10-4-262
16 Extermann M Interaction between comorbidity and cancer. Cancer Control. 14(1) 13 - 22 2007. DOI: 10.1177/107327480701400103
17 Cai X Wu H Peng J Zhu J Cai S Cai G & Zhang Z Tolerability and outcomes of radiotherapy or chemoradiotherapy for rectal cancer in elderly patients aged 70 years and older. Radiat Oncol. 8(1) 86 2013. DOI: 10.1186/1748-717X-8-86
18 Erichsen R Horváth-Puhó E Iversen LH Lash TL & Sørensen HT Does comorbidity interact with colorectal cancer to increase mortality? A nationwide population-based cohort study. Br J Cancer. 109 2005 - 2013 2013. DOI: 10.1038/bjc.2013.541
19 Roscio F Boni L Clerici F Frattini P Cassinotti E & Scandroglio I Is laparoscopic surgery really effective for the treatment of colon and rectal cancer in very elderly over 80 years old? A prospective multicentric case-control assessment. Surg Endosc. 30(10) 4372 - 4382 2016. DOI: 10.1007/s00464-016-4755-7
20 Hoshino N Fukui Y Hida K & Sakai Y Short-term outcomes of laparoscopic surgery for colorectal cancer in the elderly versus non-elderly: a systematic review and meta-analysis. Int J Colorectal Dis. 34(3) 377 - 386 2019. DOI: 10.1007/s00384-019-03234-0
21 Otsuka K Kimura T Hakozaki M Yaegashi M Matsuo T Fujii H Sato K Hatanaka T & Sasaki A Comparative benefits of laparoscopic surgery for colorectal cancer in octogenarians: a case-matched comparison of short- and long-term outcomes with middle-aged patients. Surg Today. 47(5) 587 - 594 2017. DOI: 10.1007/s00595-016-1410-9
22 Kang T Kim H Kim H Chun H Han W & Jung K Age over 80 is a possible risk factor for postoperative morbidity after a laparoscopic resection of colorectal cancer. Ann Coloproctol. 31(6) 228 2015. DOI: 10.3393/ac.2015.31.6.228
23 Bottino V Esposito M Mottola A Marte G Di Maio V Sciascia V Nunziante M Fregola G Cuzzovaglia S Galante F Andreoli F Breglia A Giuliano M Papaleo D Della Rocca P & Maida P Early outcomes of colon laparoscopic resection in the elderly patients compared with the younger. BMC Surgery. 12(S1) S8 2021. DOI: 10.1186/1471-2482-12-S1-S8
24 Thong M Koch-Gallenkamp L Jansen L Bertram H Eberle A Holleczek B Waldeyer-Sauerland M Waldmann A Zeissig S Brenner H & Arndt V Age-specific health-related quality of life in long-term and very long-term colorectal cancer survivors versus population controls - a population-based study. Acta Oncol. 58(5) 801 - 810 2019. DOI: 10.1080/0284186X.2018.1557340
25 Khan N Perera R Harper S & Rose P Adaptation and validation of the Charlson Index for Read/OXMIS coded databases. BMC Fam Pract. 11(1) 1 2010. DOI: 10.1186/1471-2296-11-1
26 von Elm E Altman DG Egger M Pocock SJ Gøtzsche PC Vandenbroucke JP & STROBE Initiative The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. PLoS Med. 4 e296 2007. DOI: 10.1371/journal.pmed.0040296
27 Roser M Ortiz-Ospina E & Ritchie H Life Expectancy, 2019. Available at: https://ourworldindata.org/life-expectancy.
28 Orimo H Ito H Suzuki T Araki A Hosoi T & Sawabe M Reviewing the definition of "elderly". Geriatr Gerontol Int. 6(3) 149 - 158 2006. DOI: 10.1111/j.1447-0594.2006.00341.x
29 Singh S & Bajorek B Defining “elderly” in clinical practice guidelines for pharmacotherapy. Pharm Pract (Granada). 12 489 2014. DOI: 10.4321/s1886-36552014000400007
30 Tabue-Teguo M Simo N Gonzalez-Colaço Harmand M Cesari M Avila-Funes J-A Féart C Amiéva H & Dartigues J-F Frailty in elderly: a brief review. Geriatr Psychol Neuropsychiatr Vieil. 15 127 - 137 2017. DOI: 10.1684/pnv.2017.0670
31 Preston SD Southall ARD Nel M & Das SK Geriatric surgery is about disease, not age. J R Soc Med. 101 409 - 415 2008. DOI: 10.1258/jrsm.2008.080035
32 Quasar Collaborative Group Gray R Barnwell J McConkey C Hills RK Williams NS & Kerr DJ Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 370 2020 - 2029 2007. DOI: 10.1016/S0140-6736(07)61866-2
33 Yamauchi N Matsuda T Sawad R Hasegawa H Yamashita K Harada H Urakawa N Goto H Kanaji S Oshikiri T & Kakeji Y Clinical significance of early recurrence after curative resection of colorectal cancer. Anticancer Res. 42 5553 - 5559 2022. DOI: 10.21873/ANTICANRES.16061
34 Fiscon V Portale G Frigo F & Migliorini G Laparoscopic resection of colorectal cancer: matched comparison in elderly and younger patients. Tech Coloproctol. 14 323 - 327 2010. DOI: 10.1007/s10151-010-0635-7
35 Liang Y Li G Chen P & Yu J Laparoscopic versus open colorectal resection for cancer: A meta-analysis of results of randomized controlled trials on recurrence. Eur J Surg Oncol. 34 1217 - 1224 2008. DOI: 10.1016/j.ejso.2007.11.004
36 Vinci A Hanna MH & Pigazzi A Minimally invasive right colectomy: challenges and clinical practice. Minerva Chir. 70 297 - 309 2015.
37 Akiyoshi T Kuroyanagi H Oya M Konishi T Fukuda M Fujimoto Y Ueno M & Yamaguchi T Short-term outcomes of laparoscopic rectal surgery for primary rectal cancer in elderly patients: is it safe and beneficial. J Gastrointest Surg. 13 1614 - 1618 2009. DOI: 10.1007/s11605-009-0961-0
38 Alley PG Surgery for colorectal cancer in elderly patients. Lancet. 356 956 2000. DOI: 10.1016/S0140-6736(00)02707-0
39 Golfinopoulos V Pentheroudakis G & Pavlidis N Treatment of colorectal cancer in the elderly: a review of the literature. Cancer Treat Rev. 32 1 - 8 2006. DOI: 10.1016/J.CTRV.2005.10.002
40 Ketelaers SHJ Fahim M Rutten HJT Smits AB & Orsini RG When and how should surgery be performed in senior colorectal cancer patients. Eur J Surg Oncol. 46 326 - 332 2020. DOI: 10.1016/J.EJSO.2020.01.007
41 Bouassida M Charrada H Chtourou MF Hamzaoui L Mighri MM Sassi S Azzouz MM & Touinsi H Surgery for colorectal cancer in elderly patients: how could we improve early outcomes. J Clin Diagn Res. 9 PC04 - PC08 2015. DOI: 10.7860/JCDR/2015/12213.5973
42 Akdeniz N Küçüköner M Kaplan MA Urakçi Z Sezgin Y Karhan O & Işikdoǧan A Survival impact of optimal treatment for elderly patients with colorectal cancer: A real world study. Indian J Cancer. 58 539 - 544 2021. DOI: 10.4103/IJC.IJC_409_19
43 Zhang Y Tan S Wang J Zhang Z & Wu G Nutrition and exercise prehabilitation in elderly patients undergoing cancer surgery. Asia Pac J Clin Nutr. 30 349 - 357 2021. DOI: 10.6133/APJCN.202109_30(3).0001
44 Hanna K Ditillo M & Joseph B The role of frailty and prehabilitation in surgery. Curr Opin Crit Care. 25 717 - 722 2019. DOI: 10.1097/MCC.0000000000000669
45 Carli F Bousquet-Dion G Awasthi R Elsherbini N Liberman S Boutros M Stein B Charlebois P Ghitulescu G Morin N Jagoe T Scheede-Bergdahl C Minnella EM & Fiore JF Effect of multimodal prehabilitation vs postoperative rehabilitation on 30-day postoperative complications for frail patients undergoing resection of colorectal cancer: a randomized clinical trial. JAMA Surg. 155 233 - 242 2020. DOI: 10.1001/JAMASURG.2019.5474
46 Wildiers H Heeren P Puts M Topinkova E Janssen-Heijnen MLG Extermann M Falandry C Artz A Brain E Colloca G Flamaing J Karnakis T Kenis C Audisio RA Mohile S Repetto L Van Leeuwen B Milisen K & Hurria A International Society of Geriatric Oncology Consensus on geriatric assessment in older patients with cancer. J Clin Oncol. 32 2595 2014. DOI: 10.1200/JCO.2013.54.8347
47 Walston J Buta B & Xue QL Frailty screening and interventions: Considerations for clinical practice. Clin Geriatr Med. 34 25 2018. DOI: 10.1016/J.CGER.2017.09.004
48 Hoogendijk EO Afilalo J Ensrud KE Kowal P Onder G & Fried LP Frailty: implications for clinical practice and public health. Lancet. 394 1365 - 1375 2019. DOI: 10.1016/S0140-6736(19)31786-6
49 Buta BJ Walston JD Godino JG Park M Kalyani RR Xue QL Bandeen-Roche K & Varadhan R Frailty assessment instruments: Systematic characterization of the uses and contexts of highly-cited instruments. Ageing Res Rev. 26 53 2016. DOI: 10.1016/J.ARR.2015.12.003