Impact of frailty on short-term postoperative outcomes in patients undergoing colorectal cancer surgery: A systematic review and meta-analysis

Table 1 Characteristics of the included studies

Refs	Study design	Country	Subject characteristics	Definitions used for frailty	Sample size	Newcastle– Ottawa score
McGovern et al[16], 2023	Retrospective cohort	United Kingdom	Age ≥ 65 yr (66%); males (55%). TNM Stage 1 and 2 (65%)	5-item mFI; mFI ≥ 2 indicated frailty	Frailty: 221. No frailty: 781	7
Sibia et al[17], 2023	Retrospective cohort	United States	Mean age of subjects around 62 yr; males (> 50%); frail patients older, had higher BMI, and with more comorbidities than nonfrail patients. Data on TNM stage not available	5-item mFI; mFI ≥ 0.4 indicated frailty	Frailty: 3606. No frailty: 13855	8
Abdelfatah et al[18], 2023	Retrospective Cohort	United States	Mean age of around 75 yr and males (51%); compared with the nonfrail patients, the frail group had an older mean age. Cancer histology-adenocarcinoma (80%). Majority underwent minimally invasive procedure (laparoscopic and robotic; 78%). Stage 0-2 (63%)	Frailty scores calculated using the revised RAI-A; score of 38 or higher considered as frail	Frailty: 123. No frailty: 288	8
Aguilar-Frasco et al[19], 2023	Retrospective cohort	Mexico	Mean age of 72 yr and males (56%); mean BMI approximately 2 kg/m2	Memorial Sloan Kettering-FI score ≥ 3 denoted frailty	Frailty: 56. No frailty: 160	7
Garcia-Perez et al[20], 2023	Retrospective cohort	Spain	Mean age of 76 yr and males (58%); majority with ASA class 2 or 3; all subjects with laparoscopic surgery	mFI developed based on the CSHA-FI, consisting of 11 variables, mFI score of ≥ 2 considered as frailty	Frailty: 46. No frailty: 126	7
Argillander et al[21], 2022	Retrospective cohort	Netherlands	Median age of 76 yr; females (55%); with ASA class 1 or 2 (78%); stage 1 or 2 (72%); laparoscopic surgery (64%); those who were frail were older, had higher ASA (3 or 4) and increased comorbidities	Groningen frailty indicator; score of ≥ 4 indicative of frailty	Frailty: 44. No frailty: 187	8
Nakao et al[22], 2022	Retrospective cohort	Japan	Median age of 70 yr; male (65%); patients with stage 2 or 3 cancer; ASA score higher in the frail group	Assessed using CFS score of ≥ 4 points- frail	Frailty: 11. No frailty: 97	7
Niemeläinen et al[23], 2021	Prospective cohort	Finland	Median age of 84 yr; females (60%); with ASA score of 3 (67%); stage 1 or 2 (72%); majority with either open surgery or conversion to open surgery (approximately 65%)	Assessed using CFS score of 5 to 9 points-frail	Frailty: 43. No frailty: 117	7
Artiles-Armas et al[24], 2021	Prospective cohort	Spain	Median age of 72 yr; males (65%); frail patients older and with more comorbidities, than nonfrail patients. Majority with TNM Stage 1 and 2 (66%); majority with open surgery (61%)	CSHA-CFS score ≥ 4 indicated frailty	Frailty: 59. No frailty: 90	7
Pata et al[25], 2021	Prospective cohort	Italy	Median age of 81 yr; males (53%); higher proportion of females, those with ASA 3 or 4 and co-morbidities in those who were frail; laparoscopic surgery (53%)	The multidimensional prognostic index; MPI score > 0.33 considered as frailty	Frailty: 34. No frailty: 70	8
Tamura et al[26], 2021	Prospective cohort	Japan	Mean age of 76 yr; male (58%); stage 0–2 (56%); laparoscopic surgery (90%)	The KCL; score of ≥ 8 was considered as frailty	Frailty: 164. No frailty: 336	7
Richards et al[27], 2021	Prospective cohort	New Zealand	Median age of 76 yr; male (50%); patients with ASA 3 or 4 (48%); Compared with the nonfrail patients, the frail group had an older median age, high ASA score and higher proportion underwent open surgery; stage 1 or 2 tumor (72%); laparoscopic surgery (57%)	Edmonton frail scale; those scoring ≥ 8 classified as frail	Frailty: 12. No frailty: 74	8
Bessems et al[28], 2021	Retrospective cohort	Netherlands	Patients older than 75 yr; females (51%); with ASA class 1 or 2 (67%); stage 1 or 2 (64%); laparoscopic surgery (75%); those who were frail were older, had higher ASA (3 or 4) and increased comorbidities	G8 and 4MGST (G8 ≤ 14 and/or 4MGST < 1 m/s) indicated frailty	Frailty: 53. No frailty: 79	8
Mima et al[29], 2020	Retrospective cohort	Japan	Majority aged < 75 yr (54%); male (53%); stage 1 or 2 (66%)	Assessed using CFS score of ≥ 4 points-frail	Frailty: 253. No frailty: 476	6
Gong and Qi[30], 2020	Retrospective cohort	China	Mean age of 68 yr; males (54%); with ASA 1 or 2 score (80%); stage 1 or 2 (63%); minimal invasive surgery (75%)	mFI developed based on the CSHA-FI, consisting of 11 variables. mFI score of ≥ 4 considered as high frailty	Frailty: 19. No frailty: 141	6
Al-Khamis et al[31], 2019	Retrospective cohort	United States	Patients aged > 50 yr and females (51%); compared with the nonfrail patients, the frail group had an older mean age, higher BMI, comorbidities (COPD, diabetes and hypertension) and high ASA score; Majority underwent open surgery (53%)	5-item mFI; mFI ≥ 2 indicated frailty	Frailty: 53230. No frailty: 135356	9
Okabe et al[32], 2019	Retrospective cohort	Japan	Median age of subjects higher in those who were frail (80 yr vs 68 yr); males (62%); laparoscopic surgery (63%); stage 1 or 2 (70%)	Assessed using CFS score of ≥ 4 points-frail	Frailty: 78. No frailty: 191	7
Pandit et al[33], 2018	Retrospective cohort	United States	Mean age of 69 yr; males (62%); majority with open surgery; those who were frail had increased comorbidities (diabetes, cardiovascular disease)	CSHA-FI; score of > 0.27 was defined as frail	Frailty: 18241. No frailty: 35411	8
Souwer et al[34], 2018	Prospective cohort	Netherlands	Median age of 77 yr; females (45%); stage 1 or 2 (65%); majority with laparoscopic surgery (76%)	G8 and ISARHP scales. Score of ≤ 14 on G8: frail. Score of ≥ 2 on ISARHP: frail	Frailty: 20. No frailty: 117	8
Reisinger et al[35], 2015	Prospective cohort	Netherlands	Mean age of 69 yr; male (50%); majority with open surgery (90%; stage 3 or 4 (> 50%)	Groningen frailty indicator; score of 5 or more labeled as frail	Frailty: 41. No frailty: 269	7
Ommundsen et al[36], 2014	Prospective cohort	Norway	Majority aged 7 to 89 yr (94%); female (57%); stage 0 to 2 (60%); open surgery (66%)	GA	Frailty: 76. No frailty: 102	6
Neuman et al[37], 2013	Retrospective cohort	United States	Mean age of 84 yr; stage 1 or 2 (72%); male (39%)	JHACG frailty-defining diagnosis indicator was used. It uses 11 categories of ICD-10 codes to predict a patient’s frailty status	Frailty: 566. No frailty: 12413	7
Tan et al[38], 2012	Prospective cohort	Multicenter (Singapore and Japan)	Mean age of around 81 yr; ASA 3 or more (31%); majority undergoing laparoscopic surgery	Based on weight loss, physical exhaustion, physical activity level, grip strength, and walking speed	Frailty: 19. No frailty: 64	6
Kristjansson et al[39], 2010	Prospective cohort	Norway	Mean age of 80 yr; females (57%); stage 0 to 2 (62%); majority with open surgery (66%)	Based on CGA	Frailty: 76. No frailty: 102	7

CGA: Comprehensive geriatric assessment; mFI: Modified frailty index; RAI-A: Risk Analysis Index; JHACG: Johns Hopkins Adjusted Clinical Groups; GA: Geriatric assessment; G8: Geriatric 8; ISARHP: Identification of Seniors at Risk for Hospitalized Patients; CSHA-FI: Canadian Study of Health and Aging Frailty Index; CFS: Clinical frailty scale; CSHA-FI: Canadian study and health and aging frailty index; 4MGST: 4-m gait speed test; KCL: Kihon Checklist; BMI: Body mass index.

Table 2 Findings of the subgroup analysis

	Mortality (30-d)	Mortality (90-d)	Mortality (1-yr)	Any complications	Major complications
	RR (95%CI) (n; I2)
Study design
Retrospective	1.85 (1.37, 2.50) (7; 57.1%)1	3.96 (0.54, 28.8) (2; 94.1%)	8.80 (6.84, 11.3) (4; 0.0%)1	2.02 (1.64, 2.49) (9; 89.9%)1	2.38 (0.93, 6.07) (4; 94.6%)
Prospective	3.94 (1.30, 12.0) (4; 19.7%)1	5.03 (1.38, 18.3) (3; 38.9%)1	1.88 (1.03, 3.41) (2; 6.1%)1	1.54 (1.33, 1.78) (6; 17.5%)1	3.23 (2.11, 4.95) (5; 32.7%)1
Tumor stage
Stage 0 to 22	3.54 (1.79, 7.02) (6; 0.0%)1	4.07 (1.14, 14.6) (4; 86.8%)1	4.29 (1.83, 10.1) (4; 87.0%)1	1.67 (1.42, 1.97) (9; 42.4%)1	2.57 (1.41, 4.66) (5; 64.7%)1
Type of surgery3
Minimal invasive	3.10 (1.33, 7.22) (5; 0.0%)1	4.61 (0.85, 25.1) (3; 65.3%)	18.8 (5.22, 67.7) (2; 0.0%)1	2.02 (1.59, 2.57) (8; 58.0%)1	3.12 (1.71, 5.68) (5; 60.2%)1
Open	1.63 (1.01, 2.63) (4; 78.7%)1	2.14 (0.71, 6.43) (1; -)	1.88 (1.03, 3.41) (2; 6.1%)1	1.51 (1.27, 1.81) (4; 60.8%)1	1.80 (1.09, 2.98) (3; 68.5%)1

¹Statistically significant at P < 0.05.

²Not all studies reported on the stage of the tumor. Furthermore, we have done this as a sensitivity analysis after excluding studies with subjects having tumor stage of 3 or more (only two studies had subjects with stage ≥ 3).

³Not all studies reported on the type of surgery.

RR: Relative risk; CI: Confidence interval.