Increased Adjuvant Therapy Use and Improved Survival in Dutch Elderly Patients with Stage III Colon Cancer: A Direct Correlation?


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Survival of elderly patients with stage III colon cancer increased over time, most likely due to stage migration caused by better diagnosis over time and increased use of adjuvant therapy.

A survival benefit of adjuvant chemotherapy has been reported for select elderly patients with stage III colon cancer, but many elderly patients are not candidates for or are not given adjuvant therapy due to comorbidities and fear of toxicity. In a recent Annals of Oncology article, van Steenbergen and colleagues reported findings in a Netherlands Cancer Registry study indicating increased use of adjuvant therapy and improved survival during recent years among elderly Dutch patients with stage III colon cancer.1 The authors suggested that the finding of improved survival likely reflects a contribution of increased stage migration, increased use of adjuvant therapy, and selection of fitter patients for adjuvant treatment in more recent years.

The study included all (N = 8,051) patients aged ≥ 75 years with resected stage III (IIIA = T1-2, N1; IIIB = T3-4, N1; and IIIC = any T, N2) primary colon cancer diagnosed from 1997 to 2009 in The Netherlands. Of these patients, 46% were aged 75 to 79 years, 33% 80 to 84 years, and 22% ≥ 85 years at diagnosis. Most were women (58%), had stage IIIB disease (58%), and had moderate/well differentiated tumor grade (67%). Proportions of patients receiving adjuvant therapy and crude 5-year survival rates were compared for the periods 1997–2000 (n = 2,156), 2001–2003 (n = 1,676), 2004–2006 (n = 1,944), and 2007–2009 (n = 2,275).

Adjuvant Therapy Use

Overall, 17% of patients received adjuvant therapy. The proportion of patients receiving adjuvant therapy increased from 12% in 1997–2000, to 15% in 2001–2003, 19% in 2004–2006, and 23% in 2007–2009 (P < .0001 for trend). The proportion of patients aged 75 to 79 years receiving adjuvant therapy doubled from 22% in 1997–2000 to 44% in 2007–2009 (P < .0001 for trend). Although relatively few patients aged 80 to 84 years received adjuvant therapy, the proportion increased from 4% in the first time period to 10% in the final time period. Overall, only 1% of patients aged 85 years or older received adjuvant therapy. Variations in chemotherapy use among the eight geographic regions were evident but decreased over time.

After stratified analysis adjusting for age, gender, tumor site, disease stage, tumor grade, period of diagnosis, and region, patients aged 75 to 79 years were significantly more likely to receive adjuvant therapy when they had more advanced disease stage (odds ratio [OR] =1.4 for stage IIIC vs stage IIIB, P < .0001) and when cancer was diagnosed more recently (OR = 1.8, P < .0001, for 2004–2006 and OR =2.8, P < .0001, for 2007–2009 vs 1997–2000). Patients in this age group were also significantly more likely to receive therapy in two of the geographic regions.

Patients ≥ 80 years of age were significantly less likely to receive adjuvant therapy if they were female (OR = 0.7, P < .05, vs men) and significantly more likely to receive therapy when disease was more advanced (OR = 2.3, P < .0001, for IIIC vs IIIB) and was diagnosed more recently (OR = 2.0, P < .05, for 2004–2006, and OR 2.4, P < .0001, for 2007–2009 vs 1997–2000). Patients from one geographic region were also more likely to receive adjuvant chemotherapy.

Improved Survival

Crude 5-year survival among all patients was 33%. Five-year survival was 58% in patients receiving adjuvant therapy, compared with 28% in those not receiving adjuvant therapy (P < .0001), with survival being greater in patients aged 75 to 79 years than in patients aged ≥ 80 years, both with and without adjuvant therapy. Factors significantly associated with poorer 5-year survival in addition to greater age were male gender, proximal tumor site, more advanced disease stage, poor tumor grade, and earlier period of diagnosis.

On multivariate analysis, adjuvant chemotherapy was the strongest predictor of survival after adjustment for patient and tumor factors, being associated with a 50% reduction in risk for death (adjusted hazard ratio [HR] = 0.5, P < .0001). Other significant predictors on multivariate analysis were age 80 to 84 years and age ≥ 85 years (poorer survival vs age 75–79 years), disease stage IIIA (better survival vs IIIB) and stage IIIC (poorer survival vs IIIB), poor tumor grade (poorer survival vs moderate/well tumor grade), and diagnosis in any period after 1997–2000 (better survival vs diagnosis in 1997–2000).

The 5-year survival rate increased from 29% in 1997–2000, to 32% in 2001–2003 (adjusted HR = 0.9, P < .05), and 35% in 2004–2006; 5-year survival could not be determined for patients diagnosed in 2007–2009, but the adjusted hazard ratio compared with 1997–2000 was 0.7 (P < .0001).

A multivariate survival model analysis without adjuvant chemotherapy showed similar results for the other variables, especially for period of diagnosis, with the exception of a stronger effect of age on survival. After stratification for adjuvant therapy, significant effects of both age and period of diagnosis were found both in patients receiving and in those not receiving adjuvant chemotherapy. Five-year disease-specific survival rates were 38% for patents aged 75 to 79 years, 27% for those aged 80 to 84 years, and 17% for those aged ≥ 85 years (P < .0001 for trend).

Among patients who died, colorectal cancer was the cause of death in 72% of patients who received adjuvant therapy and in 60% of those who did not. In the latter group, cardiovascular disease (10% vs 5%) and respiratory disease (3% vs 1%) were more common causes of death.

Stage Migration and Increased Adjuvant Therapy

The investigators hypothesized that the improvement in survival of patients with stage III colon cancer over time is likely attributable in part to stage migration associated with improvements in evaluation of lymph nodes and imaging techniques that occurred during the study period. This effect is supported by the finding that survival improved over time in models with and without adjuvant chemotherapy.

The authors also hypothesized that the reduced mortality from colon cancer in patients not receiving adjuvant therapy reflects avoidance of its use in patients with substantial comborbidities. They noted, “[T]his group might justifiably have not received adjuvant chemotherapy, especially since they died more often due to cardiovascular and respiratory diseases, which are frequent comorbidities in colon cancer patients.”

The authors concluded, “Survival of elderly patients with stage III colon cancer increased over time, most likely due to stage migration caused by better diagnosis over time and increased use of adjuvant therapy. The marked effect of adjuvant chemotherapy on survival might be caused by selection of fitter patients without comorbidity and a good performance status, which should be investigated further.”

For more on adjuvant therapy in older patients with colorectal cancer, see page 87. ■

Disclosure: The study investigators  reported no potential conflicts of interest.

Reference

1. van Steenbergen LN, Lemmens VEPP, Rutten HJT, et al: Increased adjuvant treatment and improved survival in elderly stage III colon cancer patients in The Netherlands. Ann Oncol. May 4, 2012 (early release online).



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