Table 1. Summary of study characteristics and study outcomes of articles comparing different age groups of patients (older vs. younger patients) receiving surgery for metastatic colorectal cancer.
| Ref. | Study design and time frame | Type of intervention | Number of patients | Metastasis characteristics | Neoadjuvant chemotherapy | Morbidity rate | Mortality rate | R0 resection | OS | DFS | Predictors of morbidity and survival |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Nagano et al. 2005 | Retrospective cohort study 1992–2004 |
Liver resection | 212 Older (≥70 yo) = 62 Younger (<70 yo) = 150 |
Single nodule: 34/61 Older patients vs. 93/150 Younger Metachronous lesion: 35/61 Older patients vs. 74/150 Younger (NSD) Maximum tumor size: 43.8 mm for Older vs. 35.8 mm for Younger (p = 0.071) |
Neoadjuvant hepatic arterial infusion Older: 11.3% Younger: 16% (p = 0.377) |
Older: 19.7% Younger: 23.3% (p = 0.562) |
Older: 0% Younger: 0.49% |
Older: 48.1% Younger: 52.2% (NSD) |
1-, 3-, 5-year OS Older: 79.4%, 46.5%,, 34.1% Younger: 90.6%, 62.8%, 53.1% (p = 0.01) |
5-year DFS: Older: 50.7% Younger : 46.5% (NSD) |
• The rate of non treatment for hepatic recurrence was higher in Older patients than that in younger patients (29.2% versus 10.6%; p = 0.04) • Advanced chronologic age cannot be regarded as a medical contraindication to hepatic resection for CRLM in patients ≥70 years. |
| Figueras et al. 2007 | Retrospective cohort study 1990–2006 |
Liver resection | 648 Older (≥70 yo) = 160 Younger (<70 yo) = 488 |
Synchronous metastases: 39% of Older vs. 49% of Younger (p = 0.036) Isolated CRLM: 51% of Older vs. 42% of Younger (p = 0.03). Size of the CRLM: 4.2±2.6 cm for Older vs. 3.7±2.1 cm for Younger (p = 0.009). Lesions larger than 10 cm: 5% of Older vs. 1% of Younger |
Older: 20% Younger: 27% (p = 0.06) |
Older: 41% Younger: 34% (p = 0.008) |
Older: 8% Younger: 3% (p = 0.008) |
Older: 85% |
1-, 3-, 5-year OS: Older: 82%, 48%, 36% Younger: 88%, 62%, 45% (p = 0.0069) |
1-, 3-, 5-year DFS: Older: 68%, 34%, 30% for Younger: 68%, 32%, 25% (p = 0.71) |
• Only tumoral size > 10 cm significantly increased the postoperative mortality risk in the Older group. • Only 50% of the Older patients received adjuvant chemotherapy compared to 70% in the Younger group |
| Mazzoni et al. 2007 | Retrospective single center cohort study 1987–2002 |
Liver resection Including: wedge resection, segmentectomy, right and left lobectomy |
197 Older (≥70 yo) = 53 Younger (<70 yo) = 144 |
Mean lesion size 2.8 cm in both groups. LM were multiple in 103 cases and limited to one lobe in 151 patients. All patients but 84 were treated for hepatic metachronous metastases. |
Not reported | Older: 20.7% Younger: 14.6% (p = 0.18) |
Older: 5.7% Younger: 2.1% (p = 0.19) |
Older: 83% Younger: 86.8% (NSD) |
Median OS Older : 28 months Younger: 31 months (p = 0.30) |
Not reported | • The number of Clinical Risk Score parameters and the microscopical involvement of the hepatic resectional margin were found to directly affect survival • Age by itself may not be a contraindication to surgery. |
| Mann et al. 2008 | Retrospective cohort study 1999–2005 |
Liver resection Including anatomical resections, extended procedures and extra-anatomical resections performed with curative intent |
191 Older (≥70 yo) = 49 Younger (<70 yo) = 142 |
Not reported | Not reported | Older: 30.6% Younger: 19% |
At 30 days : Older: 0% Younger: 2% At 60 days: Older: 4% Younger: 3% (NSD) |
Not reported |
1-, 3-, 5-year OS: Older: 89%, 38%, 31% Younger: . 88%, 54%, 43% (NSD) |
1-, 3-, 5-year DFS: Older: 76%, 35%, 29%, Younger: 62%, 38%, 32%, |
• Aggressive surgical policy towards CRLM in Older patients is associated with low peri-operative morbidity and mortality, as well as good long-term outcomes, thus justifying its use. |
| Adam et al. 2010 | Retrospective multicenter cohort study 1986–2008 |
Liver resection Including major and minor hepatectomies |
7764 Older (≥70 yo) = 1624 Younger (<70 yo) = 6140 |
Synchronous CRLM: 661 Older vs. 2924 Younger Metachronous CRLM: 913 Older vs. 2821 Younger Maximum diameter > 50 mm: 372 Older vs. 1302 Younger CRLM >3: 162 Older vs. 1206 Younger Bilateral CRLM: 405 Older vs. 2224 Younger |
Older: 33.9% Younger: 33.2% |
Older: 32.3% Younger: 28.7% (p<0.001) After major hepatectomy: Older: 37.8% Younger : 35.2% (p = 0.19) |
At 60 days: Older: 3.8% Younger: 1.6% (p<0.001) After major hepatectomy: Older: 5% YOunger : 2.2% (p<0.001) |
Not reported |
3-year OS: Older: 57.1% Younger: 60.2% (p< 0.001) |
3-year DFS: Older: 37% Younger: 31.9% (p = 0.051) Recurrence rate: Older: 28.1% Younger: 35.6% (p>0.001) |
• Within the Older group, preoperative CT was a risk factor for postoperative morbidity • Within the Older group: >3 CRLM at diagnosis (RR = 1.63 (95%CI: 1.13–2·36), bilateral CRLM (RR = 1.39 (1.04–1.87), and concomitant extrahepatic disease (RR = 1.56 (1.08–2.23) were predictors of mortality at 60 days |
| Di Benedetto et al. 2011 | Retrospective matched cohort study 2002–2009 |
Liver resection Associated surgery (major operations performed during the liver resection) for 15.6% Older vs. 28.1% for Younger (p = 0.05) |
64 Older (≥70 yo) = 32 Younger (<70 yo) = 32 |
Synchronous CRLM: 22 Older vs. 23 Younger |
Administered for unresectable liver metastases Older: 62.5% Younger: 81.3% |
Oder: 28.1% Younger: 34.4% (p>0.99) |
At 30 days: 0% in both groups At 60 days: Older: 3% Younger: 0% (NSD) |
75% in both groups |
1-, 3-, and 5-year OS: Older: 84.1%, 51.9%, 33.3% Younger: 93.6%, 63%, 28%, (p = 0.50) |
1-, 3-, and 5-year DFS: Older: 67.9%, 29.2%, 19.5% Younger: 57.6%, 32.9%, 16.4%, (p = 0.72) |
Not reported |
| Cannon et al. 2011 | Retrospective case-control study Not reported |
Liver resection Including synchronous resection of colon and liver; major hepatectomy (52% Older vs. 53% Younger; p = 0.9). Laparoscopy in 12.5% of Older vs. 19.8% of Younger (p = 0.3) |
279 Older (≥70 yo) = 59 Younger (<70 yo) = 220 |
Number of CRLM: 2.02 for Older vs. 2.61 for Yonger (p = 0.4) Mean size: 4.39 cm for Older vs. 4.61 cm for Younger (p = 0.1) |
Overall 58% of patients (NSD between the groups) |
Older: 52.5% Younger: 48.2% (p = 0.5) |
At 90 days: Older: 0% Younger:. 4.1% (p = 0.2) |
Older: 81.4% Younger: 88.6% (p = 0.14) |
1-, 3-, 5-year OS: Older: 91.2%, 47.6%, 20.9% Younger: 92.3%, 59.6%, 35.1% (p = 0.07) |
1-, 3-, 5-year DFS: Older: 78.3%, 22.3%, 16.7% for Younger : 74.4%, 37.9%, 18.9% (p = 0.15) |
• Need of transfusion was independent predictors of postoperative morbidity (OR for non transfused patients = 0.45 [95%CI: 0.25–0.79]) • Age was not associated with shortened OS and DFS. • Fong score and BMI <20 were independent predictors of OS • Fong score was predictor of DFS |
| Kulik et al. 2011 | Retrospective cohort study 1994–2008 |
Liver resection Including 51.8% minor and 48.2% major resections |
939 Older (≥70 yo) = 190 Younger (40–69 y.o.) = 719 Young (<40) = 29 |
Synchronous CRLM: 334 patients Unilobar CRLM: 654 patients One CRLM: 491 patients Mean size: 56.78 mm (range: 3–315 mm; SD: 39.0) |
Overall: 53.2% | Older: 12.4% Younger.. 15.3% (p = 0.24) |
Older: 0.54% Younger: 1.26% (NSD) |
Older: 96.7% Younger: 96.6% (p = 0.663) |
5-year OS: Older: 31.2% Younger: 37.5% Young: 21.6% |
Not reported | • For the whole sample, metastases diameter >50 mm, rising number of transfusions (>6) needed during surgery, duration of surgical procedure >210 min, and age ≥70 years were predictors of poorer OS. • For Older patients, the rising number of transfusions (>6) needed during surgery was an independent predictor of OS (HR: 3.64 (95%CI: 1.31–10.11) |
| Cook et al. 2012 | Retrospective cohort study 1989–2009 |
Liver resection All elective open hepatic resections |
1279 Older (≥75 yo) = 151 Younger (<75 yo) = 1292 |
Synchronous metastases: 37.1% for Older vs. 39.6% for Younger Unilateral CRLM: 76.2% for Older vs. 72.4% for Younger ≥ liver metastases: 54.3% for Older vs. 69.8% for Younger |
Older: 43% Younger: 55.7% (p = 0.003) |
Older : 32.5% Younger : 21.2% (p = 0.02) |
Older: 7.3% Younger: 1.3% (p = 0.001) |
Not reported |
Median OS: Older : 44.1 (range 38.4–56.8) months Younger : 43.6 (range 40.2–47.0) months (p = 0.697) |
Not reported | • Not reported |
| Kumar et al. 2013 | Population-based retrospective cohort study 2006–2012 |
Multi treatments Surgery (1211), hepatic metastatectomy (292), lung metastatectomy (56), CT (1291). Liver-only metastases were reported in 35.7% Older vs. 39.7% Younger |
2314 Older (≥80 yo) = 676 Younger (<80 y.o.) = 1638 |
Synchronous CRLM: 62.3% of Older vs. 65.3% of Younger >2 sites of metastatic disease: 8% of Older vs. 9.2% of Younger (NSD) |
CT: 28.1% of Older vs. 68.2% of Younger Targeted therapies with monoclonal antibodies: 2.4% of Older and 16% of Younger |
Not reported | Not reported | Not reported | Older: 8.2 months Younger: 19.2 months (p<0.0001) |
Not reported | • Older (≥80 yo) were less likely to receive intervention for their mCRC and had poorer survival. • The survival of selected Older patients who received CT was similar to the survival of those younger despite the receipt of single-agent therapy. |
| Doat et al. 2014 | Retrospective population-based national cohort study April-December 2009 |
Multi treatments Surgery of the primary tumour and metastases was significantly less frequent among Olders |
31665 Older (≥75 yo) = 13255, of which metastatic CRC: 3588 (19.5%) Younger (<75 yo) = 18410, of which metastatic CRC: 2724 (20.5%) |
Metastatic site: most frequently the liver (68% in the Younger group vs. 72% in the Older group), followed by the peritoneum (33%), lung (21%), bones (5%) and brain (1%) Synchronous metastasis: 2724 patients in the Older vs. 3588 in Younger |
Older: < 50% received palliative CT, Younger: 85% |
Not reported | Not reported | Not reported |
OS of patients with metastatic CRC: Older: 8.4 months (95%CI: 7.6–9.4) Younger: 22.3 months (95%CI: 21–24.9) |
Not reported | • Age <85 years, isolated metastasis, no bowel obstruction and Charlson Comorbidity Index ≤2, CT, liver surgery, and primary tumor resection were significant predictors of improved OS |
| Booth et al. 2015 | Population-based retrospective cohort study 2002–2009 |
Liver resection Including major (34%) and minor (64%) hepatectomies |
1310 Older (≥75 yo) = 186 Younger (65–74 yo) = 414 Young (<65) = 710 |
Not reported | Older: 14% Younger: 15% Young: 16% Peri-operative CT was less common in Older patients: 41% of Older vs. 57% of Young er, vs. 71% of young patients (p<0.001). |
Not reported |
At 30 days: Older: 5% Younger: 3% Young: 1% (p = 0.005) At 90 days: Older: 8% Younger: 5% Young: 2% (p<0.001) |
Not reported |
5-year OS: Older: 28% Younger: 44% Young: 49% (p<0.001). 10-year OS: Older: 12% Younger: 23% Young: 35% (p<0.001) |
Not reported | • Increasing age and major hepatectomy were independent predictors of mortality at 30 days • Resection of CRLM is associated with greater risk of postoperative mortality among Older patients despite less aggressive treatment. |
| Nomi et al. 2015 | Retrospective single center matched case control study 1998–2013 |
Liver resection All resections were performed with curative intent |
93 Older (≥70 yo) = 31 Younger (<70 yo) = 62 |
CRLM size ≥ 5 cm: 32.3% of Older vs. 29% of Younger Median number of lesions: 2 (range: 1–8) for Older vs. 2 (1–6) for Younger (NSD) |
Older: 58.1% Younger: 75.8% (p = 0.09) |
Older: 41.9% Younger: 54.8% (p = 0.276) |
At 90 days: 0% for both groups | Older: 83.9% Younger: . 95.2% (p = 0.116) |
3-year OS: Older: 57.9% Younger: 61.7% (p = 0.842) |
3-year DFS: Older: 38.5% Younger: 35.3% (p = 0.676) |
• Laparoscopic major hepatectomy for CRLM could be safely performed in Older patients • Advanced age itself should not be regarded as contraindication for liver surgery |
| Parakh et al. 2015 | Population-based retrospective cohort study 2009–2014 |
Multi treatments: Surgical resection of metastatic disease occurred in 21% of patients, declining with advancing age (26% in Younger vs. 21% in Older vs. 6% in very old, p<0.001) |
821 Very old (≥85 yo) = 106 Older (75–84 yo) = 352 Younger (65–74) = 363 |
Metastatic site: liver (62%), lung (32%), bone (3%), brain (1.5%) Synchronous metastatic disease: 58% patients No age-related differences |
Overall 23% of patients, with differences between age groups (only 34% of very old received neoadjuvant CT) |
Not reported | Not reported | Not reported |
Median OS: Very old: 11 months Older: 20 months Younger: 26 months (p<0.001) |
Not reported | • Longer median survival was observed for patients who received CT across each of the age groups, though not reaching statistical significance in those ≥85 years (p = 0.061) • >Older patients (aged 75–84) (HR: 1.33, 95%CI: 1.09–1.63) and very old (aged ≥ 85 years) (HR: 2.39, 95%CI: 1.80–3.16) had a poorer OS than Younger patients (aged 65–74 years) |
| Nachmany et al. 2016 | Retrospective cohort study 2010–2015 |
Liver resection 25% by laparoscopy (22.5% in the Older vs. 27.7% in the Younger, p = 0.49). Major liver resection: 20.3% in Older vs. 34.1% in Younger (NSD) |
174 Older (≥70 yo) = 54 Younger (<70 y.o.) = 120 |
Number of metastasis: 1.7 (SD: 1.38) for Older vs. 2.96 (SD: 2.86) for Younger (p = 0.003) Maximal lesion size: 37 mm (SD: 25.9) for Older vs. 32.9 mm (SD: 26.3) for Younger (p = 0.18) Bilobar disease: 16.6% for Older vs. 33.3% for Younger (p = 0.07) |
Older: 55.5% Younger: 76.6% (p = 0.13) | Older : 11.1% Younger: 2.5% r (p<0.0001) |
At 60 days: Older: 1.8% |
Older: 90% Younger: 86% (p = 0.14) |
3-year OS: NSD |
3-year OS: NSD | Not reported |
| Nardo et al. 2016 | Retrospective multicenter cohort study 2008–2015 |
Liver resection |
149 Very old (≥75 yo) = 21 Older (65–74 yo) = 79 Younger (<65) = 49 |
Unilobar liver metastases: 16.7% in the very old group vs. 21.1% in the Older vs. 28.6% in the Younger Mean lesion size: 4.6 cm for very old vs. 4.5 cm for Older vs. 4.1 cm for Younger (NSD) |
Very old: 14.3% Older: 16.5% Younger: 16.3% (p = 0.97) |
Very old: 24.1% Older:. 24% Younger: 22.4% (p = 0.86) |
At 30 days: Very old: 4.8% Older: 2.5% Younger: 0% (p = 0.8) At 60 days: Very Old: 4.8% Older: 3.8% Younger: . 2% (p = 0.8) |
Very old: 90.5% Older: 90.1% Younger: 93.9% (p = 0.83) |
1-, 3- and 5-year OS: Very old: 85.7%, 38.9%, 28.6% Older: 89.9%, 38%, 33.3% Younger: 87.6%, 53.5%, 43.5% (NSD) |
1-, 3- and 5-year DFS: Very old: 76.2%, 31.3%, 20% Older: 75.9%, 35%, 28.6% Younger: 77.1%, 37.6%, 36.4% (NSD) |
• Advanced chronological age cannot be considered a medical or surgical contraindication to hepatic resection for CRLM |
| Gandy et al. 2018 | Retrospective cohort study 2007–2014 |
Liver resection The majority of patients in both groups (64% and 62%) underwent major liver resections (>3 segments) |
187 Older (≥75 yo) = 29 Younger (<75 y.o.) = 158 |
Not reported | Older: 52% Younger: 69% (p = 0.71) |
Older: 13.8% Younger: 16.5% (p = 0.65) |
1 patients per group (NSD) |
Not reported |
1-, 3-, 5-year OS: Older: 92.3%, 67.3%, 57.7% Younger: 95.1%, 72.9%, 55.6% (p = 0.6) |
Not reported | Not reported |
| Yue et al. 2018 | Retrospective single center cohort study 2009–2016 |
Liver resection All laparoscopic hepatectomiesincluding left lateral sectionectomy, sectionectomy, wedge resections |
241 Older (≥70 yo) = 78 Younger 60–69 y.o.) = 163 |
Largest lesion size: 2 cm (1–4) for Older vs. 3 cm (1–5) for Younger (p = 0.128) Number of lesions: 2 (1–3) for Older vs. 2 (1–4) for Younger (p = 0.20) |
Older: 88.4% Younger: 72.3% (p = 0.005) |
At 90 days: Older: 26.9% Younger: 23.3% (p = 0.5) |
At 90 days: 1 patient per group (overall: 0.8%) |
100% for both groups |
5-year OS: Older: 52% Younger: 59%, (p = 0.139) |
5-year DFS: Older: 45% Younger: 49% (p = 0.09) |
• TNM stage, disease-free interval, and number of metastases were independent predictors of OS • Disease-free interval and preoperative carcinoembryonic antigen levels were independent predictors of DFS • Age did not independently predict OS or DFS |
| Zarzavadjian Le Bian et al. 2019 | Retrospective cohort study 2008–2017 |
Liver resection All laparoscopic procedures Local radiotherapy was performed in 34% of rectal cancers |
335 Very old (>75 yo) = 52 Older (65–75 yo) = 136 Younger (55–65 yo) = 113 Young (< 55 yo) = 34 |
Synchronous liver metastases: 154 patients Bilobar metastasis: 107 patients More than 5 CRLM: 19 patient |
Overall, 47.5% of patients | Very old: 9.6% Older: . 7.4% Younger: 12.4% Young: 17.6% (p = 0.287) |
At 90 days: 0% |
Not reported | Not reported | Not reported | Not reported |
NSD stands for non significantly different.