Where are the inequalities in colorectal cancer care in a country with universal healthcare? A systematic review and narrative synthesis

Study selection

The database searches yielded 7201 studies, 214 of which were retrieved for full-text screening. An additional six studies were identified from the grey literature. Overall, 41 studies were included (figure 1).11

Figure 1
Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of included studies.

Study characteristics

The characteristics of the included studies are summarised in online supplemental appendix S7. The system interval was examined in 12 studies, with 7 different time points evaluated, summarised in figure 2.12–23 In total, 15 studies reported the receipt of surgery,19 20 24–36 7 studies evaluated surgical variation,37–43 14 studies reported the receipt of chemotherapy,19 20 24–27 44–51 7 reported the receipt of radiotherapy19 20 25–27 43 52 and 2 reported the receipt of any treatment.17 46

Figure 2
Figure 2

Time intervals evaluated in the included studies. The blue dotted line indicates the system interval defined by the Aarhus statement. Studies that included any aspect of this system interval were included, even if the interval commenced before the system interval defined here.

In total, 32 of the 41 studies adjusted or stratified for at least one other factor.12–26 32–41 44–49 51 The remaining nine studies provided unadjusted rates.27–31 42 43 50 52

Risk of bias in studies

Assessments of the risk of bias are summarised in figure 3 and online supplemental appendix S6. The domain most at risk of bias was study confounding, with 16 studies at high risk of bias.13 27–31 39–43 47–50 52 Although some of these studies conducted adjusted analyses, important factors such as stage were unaccounted for.

Figure 3
Figure 3

Risk of bias in the included studies. For each element the proportion of studies with high, moderate and low risk of bias is illustrated.

Results of studies reporting variations in the system interval

Referral to first-seen interval

Three studies evaluated the referral to first-seen interval.13 15 18 Two studies estimated the odds of being seen by a specialist within 2 weeks of referral; one demonstrated reduced unadjusted odds (OR 0.80, 95% CI 0.70 to 0.91),18 while there was no significant association in the other (OR 0.95, 95% CI 0.87 to 1.03) after adjusting for age, stage and site (colon vs rectal) (online supplemental appendix S8).15

Another study used generalised linear modelling to estimate the association between occupation and the number of days to see a specialist after referral, adjusting for age, marital status and ethnicity.13 This study reported no significant association (p>0.05).13 Overall, the evidence was inconclusive for an association between deprivation and the referral to first-seen interval (table 1 and online supplemental appendix S8).

Table 1

Narrative synthesis—assessment of the relationship between deprivation, the system interval and treatment received

First-seen to diagnosis interval

One study estimated the association between occupation and the number of days from the first hospital appointment to communication of diagnosis.13 A significant association was demonstrated (p=0.028), but no magnitude or direction of effect was provided. The evidence was, therefore, inconclusive (table 1 and online supplemental appendix S8).

Diagnosis to treatment interval

Five studies evaluated the diagnosis to treatment interval.14–18 Two estimated the number of days from diagnosis to major surgery, adjusting for stage, sex, age, grade and morphology.14 16 There was no significant impact of deprivation on the length of the diagnosis to treatment interval demonstrated in these two studies (coefficient 0.99, 95% CI 0.97 to 1.02)14 (coefficient 0.21, 95% CI −0.55 to 0.98) (online supplemental appendix S8).16

Two studies evaluated the likelihood of commencing treatment within 31 days from the date a treatment plan was agreed on.15 18 One study demonstrated increased unadjusted odds (OR 1.28, 95% CI 1.14 to 1.44),18 while the other presented reduced adjusted odds of patients from the most deprived areas commencing treatment within 31 days (OR 0.91, 95% CI 0.84 to 0.98) (online supplemental appendix S8).15

Another study calculated the likelihood of treatment for the most deprived quintile across several time points. They demonstrated reduced adjusted odds of treatment within 1 week (OR 0.78, 95% CI 0.72 to 0.84), 1 month (OR 0.84, 95% CI 0.78 to 0.90) and 2–3 months (OR 0.91, 95% CI 0.85 to 0.98) but non-reduced odds at 4–6 months (OR 1.07, 95% CI 0.96 to 1.18) after the first contact with the health system (online supplemental appendix S8).17

Overall, the evidence for an association between deprivation and length of the diagnosis to treatment interval was inconclusive (table 1 and online supplemental appendix S8).

Test to diagnosis interval/secondary care diagnostic interval (SCDI)

One study evaluated the SCDI, defined as the period between the date of the first interaction with secondary care and the date of diagnosis.12 This study evaluated the factors associated with an interval greater than the median, adjusting for sex, age, stage, comorbidities, ethnicity, route to diagnosis and additional diagnostic tests.12 The odds of a longer interval were not significantly increased for patients from the most deprived quintile (OR 1.07, 95% CI 1.00 to 1.13) (online supplemental appendix S8).

Another study evaluated the time from the first investigation to cancer diagnosis.23 The authors conducted quantile regression, adjusting for age, comorbidities, sex, test type and symptom category, focusing on the median and 75th centiles.23 There was no significant association between deprivation and interval length (coefficient 0.7, 95% CI −2.7 to 4.1) (online supplemental appendix S8).

Overall, there was no evidence of a prolonged SCDI or test-to-diagnosis interval for patients from the most deprived background (table 1 and online supplemental appendix S8).

First presentation to diagnosis interval

Three studies evaluated the time from the first symptom or feature of colorectal cancer in primary care records to diagnosis.21–23 One study demonstrated an association between deprivation and a longer interval in two of three econometric analyses (pre-to-post difference-in-differences 95% CI −0.03 to 0.2 and p=0.147 or event-study difference-in-differences 95% CI 0.002 to 0.136 and p=0.043 or semiparametric varying-coefficient analysis significance stated but not reported).21 The other two studies conducted quantile regression, focusing on the median and 75th centiles, adjusting for age, comorbidities, sex and type of symptom.22 23 Both studies demonstrated an association between the most deprived quintile and a longer first presentation to diagnosis interval for patients with colon cancer (eg, adjusted median interval of 204 vs 126 days, p=0.04).22 Meanwhile, there was no such association among patients with rectal cancer,23 possibly reflecting that patients with rectal cancer are more likely to present with localising symptoms (online supplemental appendix S8).

Overall, three robust studies provided evidence that patients from the most deprived quintile experienced a longer first presentation to diagnosis interval (table 1 and online supplemental appendix S8).

Symptom to diagnosis interval

One study estimated the effect of occupation on the time between a patient’s first symptom and diagnosis.13 No significant effect was demonstrated, adjusting for ethnicity, age, marital status and sex (p>0.05) (table 1 and online supplemental appendix S8).13

Referral to treatment interval

Four studies evaluated the time from referral to treatment.15 18–20 Two studies demonstrated no significant association between deprivation and the likelihood of commencing treatment within 62 days of referral (range of ORs 1.02–1.07).18 19 Another study demonstrated reduced odds of patients commencing treatment within 62 days of referral, adjusted for age, stage, referral interval and first treatment received (OR 0.82, 95% CI 0.74 to 0.91) (online supplemental appendix S8).15

Meanwhile, one study estimated HRs for the time between referral and first treatment, adjusting for stage, distance and presentation.20 There was no significant association between deprivation and time to treatment (HR 1.24, 95% CI 0.93 to 1.67) (online supplemental appendix S8).

Overall, the association between deprivation and this interval was inconclusive (table 1 and online supplemental appendix S8).

Results of studies reporting treatment inequalities

Results of studies reporting likelihood of receipt of primary surgery

The outcome of interest was primary surgery in 11 studies, here defined as resection of the tumour.19 20 24–31 36 Five studies clearly defined the outcome as a tumour resection,25 27–29 36 while the received surgical procedure was not identified in the other six studies (online supplemental appendix S9).19 20 24 26 30 31

Across seven studies, adjustment was made for different factors: age,19 20 24–26 29 36 stage,19 20 24–26 36 sex,19 24–26 29 36 comorbidity,24 25 36 site (colon vs rectum),19 25 36 distance or time to hospital,20 26 year of diagnosis,24 36 region19 and histology, grade and presentation.36 Meanwhile, four studies provided only rates of patients receiving surgery (online supplemental appendix S9).27 28 30 31

Six studies presented reduced odds of surgery for patients from the most deprived background (range of ORs 0.32–0.99).24 26–28 30 31 One study presented increased odds of not receiving surgery among the most deprived patients with rectal cancer (OR 1.35, 95% CI 1.22 to 1.49) but no significant association among patients with colon cancer (OR 0.96, 95% CI 0.87 to 1.07).36 Meanwhile, three studies demonstrated no association (range of ORs 0.52–0.88).19 20 29

One study revealed a higher likelihood of surgery for patients from the most deprived background (OR 1.63, 95% CI 1.17 to 2.26).25 Additionally, the study reported increased odds of surgery in older age groups. These findings, which were unexpected, were confirmed by consulting the author. However, it is important to note that this analysis was based on regional data from a historical cohort of colorectal cancers diagnosed between 1997 and 2004. While the reported methodology appears robust, the results of this small study are opposed to other studies (see figure 4) and cautious interpretation is required.

Figure 4
Figure 4

Forest plot demonstrating the odds of receipt of surgery in the most deprived versus the least deprived patient group.

Figure 4 displays a forest plot, which provides an overview of the findings from multiple studies investigating the likelihood of undergoing surgery for colorectal cancer. The plot reveals that a majority of studies considering primary surgery (10/12) indicate a decrease in the likelihood of surgical intervention among patients belonging to the most deprived group. Overall, the evidence strongly supports the hypothesis that patients from the most deprived group are less likely to receive surgery (table 1 and online supplemental appendix S9).

Results of studies reporting likelihood of receipt of surgery for oligometastatic disease

Four studies examined the receipt of surgery in presumed oligometastatic disease, all adjusted for age, stage, comorbidity and site (colon vs rectal).32–35 Three studies examined the receipt of liver resection, demonstrating significantly reduced odds of resection for patients from the most deprived group (range of ORs 0.70–0.76).32–34 One study examined the receipt of pulmonary resection, with no significant association demonstrated between deprivation and the likelihood of resection (OR 1.04, 95% CI 0.89 to 1.22) (table 1 and online supplemental appendix S9).35 and Figure 4 displays a forest plot, providing an overview of the findings from these studies, each highlighted with an asterisk.

Results of studies reporting likelihood of surgical variation

Seven studies evaluated variations in surgery.37–43 Six reported rates or odds of abdominoperineal resection (APER) or anterior resection (AR).37–42 Five studies adjusted for variables, including age,37–40 sex,37–41 stage,37 38 year of diagnosis or resection,37–41 surgeon workload37 38 and admission type.37–40 Online supplemental appendix S10 displays a forest plot, providing an overview of the findings from these studies. Five of the seven studies demonstrated that APER was significantly more likely than AR for patients from the most deprived areas (range of ORs 1.37–1.64) (table 1 and online supplemental appendix S11).37 39–42

Meanwhile, one study of 120 patients presented unadjusted rates of total pelvic exenteration (TPE) compared with partial pelvic exenteration.43 There was a non-significant association between deprivation and the unadjusted odds of TPE (OR 1.75, 95% CI 0.55 to 5.68) (table 1 and online supplemental appendix S11).

Results of studies reporting likelihood of receipt of chemotherapy

In total, 13 studies examined whether patients received any chemotherapy,19 20 24–27 44–50 11 of which conducted adjusted analyses.19 20 24–26 44–49 Six studies evaluated the use of adjuvant chemotherapy.24 44 45 49–51 Two studies evaluated the use of palliative chemotherapy.24 46 Meanwhile, the intent of chemotherapy was unknown in the remaining seven studies.19 20 25–27 47 48

Online supplemental appendix S12 displays a forest plot, providing an overview of the findings from the studies. Eight studies demonstrated reduced adjusted odds of chemotherapy for patients from the most deprived group (range of ORs 0.44–0.99).19 24–26 44 45 47 48 One study demonstrated reduced adjusted odds for patients from the most deprived group with colon (OR 0.45, 95% CI 0.27 to 0.77) but not rectal cancer (OR 0.73, 95% CI 0.36 to 1.50).46 Two studies did not show a significant association between deprivation and receipt of chemotherapy (range of ORs 0.49–2.13) (online supplemental appendix S13).20 49

Meanwhile, two studies presented unadjusted rates.27 50 One demonstrated reduced odds of chemotherapy for the most deprived patients with colorectal cancer (OR 0.31, 95% CI 0.09 to 0.91).50 The other demonstrated reduced odds of chemotherapy for the most deprived patients with colon (OR 0.85, 95% CI 0.81 to 0.89) but not rectal cancer (OR 1.03, 95% CI 0.95 to 1.11) (online supplemental appendix S13).27

One study examined the receipt of combination versus single-agent chemotherapy, adjusting for age, sex, ethnicity, tumour size, lymph node yield and year of diagnosis.51 However, no adjustment was made for comorbidity. Patients from the most deprived area had significantly reduced odds of receiving combination chemotherapy (OR 0.50, 95% CI 0.42 to 0.59) (online supplemental appendix S13).51

Five of the six studies evaluating the use of adjuvant chemotherapy demonstrated inequalities.24 44 45 50 51 Meanwhile, both studies evaluating the use of palliative chemotherapy demonstrated similar inequalities.24 46 Overall, the evidence strongly supports the hypothesis that patients from the most deprived group are less likely to receive chemotherapy or combination adjuvant chemotherapy (table 1 and online supplemental appendix S13).

Results of studies reporting likelihood of receipt of radiotherapy

Seven studies reported receipt of radiotherapy by socioeconomic group.19 20 25–27 43 52 Two studies evaluated the use of neoadjuvant radiotherapy.19 43 One study evaluated patterns of preoperative and postoperative radiotherapy.52 The intent of radiotherapy was unknown in four studies.20 25–27

Three studies conducted analyses that adjusted for important factors, including age,20 25 26 stage,20 25 26 sex,25 26 distance or journey time,20 26 tumour site (colon vs rectum)20 and comorbidity.25 None of these studies demonstrated a significant association between deprivation group and radiotherapy (range of ORs 0.85–0.99). Online supplemental appendix S14 presents a forest plot, providing an overview of the findings from these studies. The remaining four studies reported unadjusted rates of radiotherapy.19 27 43 52 Two of these studies demonstrated increased odds of radiotherapy for patients from the most deprived group (range of ORs 1.33–1.39).27 52 The other two studies looked at rates of neoadjuvant radiotherapy specifically and did not show a significant association between deprivation and odds of treatment (range of ORs 1.00–1.15) (online supplemental appendix S15).19 43

Overall, there was no evidence to support an association between socioeconomic status and receipt of radiotherapy (table 1 and online supplemental appendix S15). This conclusion may depend on the intent of radiotherapy and would, therefore, have been stronger if all outcomes were differentiated by intent (eg, neoadjuvant or palliative).

Results of studies reporting receipt of any treatment

Two studies evaluated the likelihood of any treatment by deprivation quintile, adjusting for age,17 46 sex46 and stage.17 46 It was assumed this meant receiving surgery, radiotherapy or chemotherapy. However, these outcomes needed to be more clearly defined. For the most socioeconomically deprived quintile, both studies reported significantly reduced odds of any treatment within 6 months of diagnosis46 or 6 months of the first contact with the NHS (range of ORs 0.54–0.87) (table 1 and online supplemental appendix S16).17

This post was originally published on https://bmjopen.bmj.com