Lifestyle after colorectal cancer diagnosis: Observed changes and associations with recurrence and survival

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. It is well accepted that CRC risk is highly modifiable through diet and lifestyle, but it is unclear whether diet and lifestyle after CRC diagnosis can impact prognosis. The aims of this thesis were to assess changes in lifestyle after diagnosis and to assess associations between lifestyle and cancer outcomes among CRC patients with stage I-III disease. The analyses are based on prospective cohort studies among CRC patients.

In chapter 2, we examined pre-to-post diagnosis changes in body weight and compared them between those treated with and without adjuvant chemotherapy. We used data of 1184 participants of the COLON study. Body weight was repeatedly self-reported in the two years following diagnosis. At diagnosis, participants also reported usual weight two years before diagnosis. Post-diagnosis weight gain (21%) was more common than weight loss (9%). However, post-diagnosis weight gain was only common among patients who lost ≥5% weight before diagnosis. Clinically relevant weight gain after CRC diagnosis was, on average, absent in the participants without pre-diagnosis weight loss. Overall, hardly any pre-to-post diagnosis weight change was observed. Pre-to-post diagnosis weight change was similar in CRC patients treated with  and without adjuvant chemotherapy (-0.1 kg, 95%CI -0.8, 0.6 versus -0.9 kg, 95%CI -1.4, -0.5).

In chapter 3, we assessed changes in lifestyle behaviors and overall lifestyle in the first two years following CRC diagnosis. We analyzed changes in overall lifestyle by assessing concordance with the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations among 1072 participants from the COLON study. In the two years following CRC diagnosis largest changes were noted for sugary drinks (-45 g/day) and red & processed meat intake (-62 g/week). BMI (+0.4 kg/m2), waist circumference (+2 cm), and dietary fiber intake (-1 g/day) changed slightly. Half of participants made simultaneous changes that resulted in both improved concordance with one component and deteriorated concordance with another component of the lifestyle score. Overall lifestyle hardly changed from a mean 3.4 ± 0.9 at diagnosis to 3.5 ± 0.9 two years after diagnosis. Our findings provided little evidence that a CRC diagnosis triggers lifestyle changes over and above lifestyle trends in the general adult population.

The association between physical activity and recovery of physical functioning after CRC surgery was assessed among 327 participants of the COLON study (chapter 4). Both physical activity and physical functioning were self-reported shortly after diagnosis and six months later. Higher post-surgery levels of physical activity were associated with improved recovery of physical function (Ptrend=0.01). In contrast, activity levels before surgery were not associated with recovery (Ptrend=0.24). An increase in physical activity after CRC surgery was associated with improved recovery of physical functioning (PR 0.57, 95%CI 0.39-0.82) compared with stable activity levels. This benefit was seen regardless of physical activity level before surgery.

The review presented in chapter 5 summarizes the literature regarding diet, physical activity, smoking, and body composition after CRC diagnosis in relation to all-cause mortality, CRC-mortality, and recurrence.

In chapter 6, we examined associations of post-diagnosis lifestyle and change in lifestyle after CRC diagnosis with recurrence and all-cause mortality. We used data of 1425 participants from the COLON and EnCoRe study. Lifestyle was assessed at diagnosis and six months post-diagnosis. We assigned lifestyle scores based on concordance with two sets of cancer prevention guidelines ─ from WCRF/AICR and the American Cancer Society (ACS) ─ and national disease prevention guidelines. Higher scores indicate healthier lifestyles. No associations were observed for CRC recurrence. A post-diagnosis lifestyle more consistent with the ACS recommendations was associated with lower all-cause mortality risk (HR per +1 SD: 0.85, 95%CI 0.73, 0.995). The same tendency was observed for higher WCRF/AICR (HR +1 SD 0.92, 95%CI 0.78, 1.08) and national (HR +1 SD 0.90 (95%CI 0.77, 1.05) lifestyle scores, although these associations were statistically nonsignificant. Improving one’s lifestyle after diagnosis (+1 SD) was associated with a lower all-cause mortality risk for the ACS (HR 0.80, 95%CI 0.67, 0.96) and national (HR 0.84, 95%CI 0.70, 0.999) scores, yet was statistically nonsignificant for the WCRF/AICR score (HR 0.94, 95%CI 0.78, 1.13).

In chapter 7, we identified the relative importance of various lifestyle behaviors, either included in healthy lifestyle recommendations or not, for CRC recurrence and all-cause mortality. Lifestyle behaviors were assessed six months after CRC diagnosis. These behaviors were simultaneously analyzed with Random Survival Forests (RSFs), a data-driven method, for 1180 participants of the COLON study. RSF identified sugary drink intake as most important lifestyle behavior regarding recurrence. Higher intakes were associated with increased recurrence risk. For all-cause mortality, fruit & vegetable, liquid fat & oil, and animal protein intake were identified as most important lifestyle behaviors. These behaviors showed non-linear associations with all-cause mortality.

In conclusion, our findings together with previous studies, suggest that lifestyle after colorectal cancer diagnosis is associated with all-cause mortality. It remains unknown if lifestyle after CRC diagnosis is associated with recurrence risk, because only few studies included this outcome. Generally, a judgement of strong evidence is needed to translate findings of prospective observational studies to evidence-based lifestyle recommendations. Based on the available studies, CRC survivors could be advised to be physically active to improve physical functioning and prolong survival. However, it is too early to formulate specific dietary recommendations for colorectal cancer survivors as the number of studies is limited and there are several factors that limit interpretation of the available studies. These limitations include: lack of a specific outcome of interest, reverse causality, confounding by treatment, timing of exposure assessment, and biological plausibility linking lifestyle with CRC prognosis.