On 2017 Feb 03, Alfonso Leiva commented:

I would like to remark this study is the first prospective cohort to analyse the assotiation between time to diagnosis and stage. Fiona Walter et al studied the factors related to longer time to diagnosis and tried to explain the lack of assotiation between longer time to diagnosis and stage. We have recently published an article to explain this paradox and suggest confounding by an unknown factor as a posible explination. We have suggested the stage when symptoms appear is the main confounder in the assotiation between time to diagnosis and stage of diagnosis and propose a graphic representation for the progression of CRC fron an preclinical asymtomatic stage to a clinical symptomatic stage.

Leiva A, Esteva M, Llobera J, Macià F, Pita-Fernández S, González-Luján L, Sánchez-Calavera MA, Ramos M. Time to diagnosis and stage of symptomatic colorectal cancer determined by three different sources of information: A population based retrospective study. Cancer Epidemiol. 2017 Jan 23;47:48-55.

On 2016 Nov 17, BSH Cancer Screening, Help-Seeking and Prevention Journal Club commented:

The HBRC discussed this paper during the journal club held on November 15th 2016. This paper fits well with research conducted within our group on early diagnosis and symptomatic presentation. We considered this paper to be a useful addition to the literature and the paper raises some interesting findings which could be investigated further.

The study examined the factors associated with a colorectal cancer (CRC) diagnosis and time to diagnosis (TDI). These factors included symptoms, clinical factors and sociodemographic factors. Due to the important role early diagnosis plays in survival from CRC, it is pertinent to investigate at which point diagnosis may be delayed. Early diagnosis of CRC can be problematic due to many of the symptoms being able to be associated with other health problems or being benign. The authors acknowledge that most cases of CRC present symptomatically.

The group was interested in the finding that less specific symptoms such as indigestion or abdominal pain were associated with shorter patient intervals and that specific classic symptoms, such as rectal bleeding were associated with shorter health system intervals (HSI). So what patients might perceive to be alarm symptoms differs from perceptions of healthcare professionals. It was also highlighted that there was a discrepancy in the patient interval found in this study with a previous study, with this study showing 35 days as the median patient interval, compared to a primary care audit conducted by Lyratzopoulos and colleagues (2015) which showed a patient interval of 19 days. It was also interesting that family history of cancer was associated with a longer HSI, given that family history is a risk factor for cancer.

The main advantage of this study is the prospective design, with the recruitment of patients prior to their diagnosis. Patients reported their symptoms and so provided insight into what they experienced, but the group did acknowledge that this was retrospective as symptoms were those experienced before they presented at the GP, with these being up to 2 years before diagnosis. The group felt the authors’ use of multiple regression models was a benefit to the study, allowing an investigation into time-constant and duration-varying effects, as in line with previous research, it was shown that rectal bleeding becomes normalised over time.

We discussed limitations of the study and recognised that the authors did not acknowledge the Be Clear on Cancer Awareness Campaigns which took place during the data collection (Jan-March 2011, Jan-March 2012, Aug-Sept 2012) and could have had an impact by shortening patient interval and increasing referral rates. We also discussed that there could be an inherent bias in GPs and that HSI could be due to this bias of GP’s wanting to reassure patients that their symptom is likely to be the sign of something other than cancer. This could also help explain the longer time to diagnosis and HSI in those with depression and anxiety, as GP’s may feel the need to over reassure these patients, recognising that they are already anxious. However, when symptoms have been shown to be a ‘false alarm’, overreassurance and undersupport from healthcare professionals has been shown to lead patients to interpret subsequent symptoms as benign and express concern about appearing hypochondriacal (Renzi, Whitaker and Wardle, 2015). It may also be due to healthcare professionals attributing symptoms to some of the side effects related to medication for depression and anxiety such as diarrhoea, vomiting, and constipation. The authors suggest also that healthcare professionals might not take these patients physical symptoms seriously. There was also a small number of CRC patients given the amount of patients approached, with the authors recognising the study is underpowered. There may also have been an overestimate of the number of bowel symptoms in non-cancer patients, which was recognised by the authors. It was also unclear that the authors had also conducted univariate analyses and that these were included in the supplementary material until they were mentioned at the end of the results.

There may also be differences in TDI depending on the type of referral e.g. two week wait, safety netting, and the group would have liked some more information about this. The group would also have liked to see some discussion about the median HSI being longer (58 days) than the 31 days currently recommended for diagnosis from the day of referral and the new target for 2020 of 28 days from referral to diagnosis. It would have also been useful to have some information about how many consultations patients had before being referred, as the authors state in the introduction that 1/3 of CRC patients have three or more consultations with the GP before a referral is made. It would also have been informative for the data on how long participants took to return their questionnaire, with the authors stating that most were completed within 2 weeks, but that some were within 3 months.

It would be interesting to look further into the factors affecting patients presenting to their GP straight away with symptoms and those which delay. We discussed possible explanations being personality, extreme individual differences in how symptoms are perceived as serious or not and external factors such as being too busy. It would also be interesting to consider whether these symptoms were mentioned by patients as an afterthought at the end of a consultation about something else, or whether this was the symptom that patients primarily presented to the doctor with.

In conclusion, the HBRC group read the article with great interest and would encourage further studies in this area.

Conflicts of interest: We report no conflict of interests and note that the comments produced by the group are collective and not the opinion of any one individual.

References

1) Lyratzopoulos G, Saunders CL, Abel GA, McPhail S, Neal RD, Wardle J, Rubin GP (2015) The relative length of the patient and the primary care interval in patients with 28 common and rarer cancers. Br J Cancer 112(Suppl 1): S35–S40.

2) Renzi C, Whitaker KL, Wardle J. (2015) Over-reassurance and undersupport after a 'false alarm': a systematic review of the impact on subsequent cancer symptom attribution and help seeking. BMJ Open. 5(2):e007002. doi: 10.1136/bmjopen-2014-007002.

On 2016 Nov 17, BSH Cancer Screening, Help-Seeking and Prevention Journal Club commented:

The HBRC discussed this paper during the journal club held on November 15th 2016. This paper fits well with research conducted within our group on early diagnosis and symptomatic presentation. We considered this paper to be a useful addition to the literature and the paper raises some interesting findings which could be investigated further.

The study examined the factors associated with a colorectal cancer (CRC) diagnosis and time to diagnosis (TDI). These factors included symptoms, clinical factors and sociodemographic factors. Due to the important role early diagnosis plays in survival from CRC, it is pertinent to investigate at which point diagnosis may be delayed. Early diagnosis of CRC can be problematic due to many of the symptoms being able to be associated with other health problems or being benign. The authors acknowledge that most cases of CRC present symptomatically.

The group was interested in the finding that less specific symptoms such as indigestion or abdominal pain were associated with shorter patient intervals and that specific classic symptoms, such as rectal bleeding were associated with shorter health system intervals (HSI). So what patients might perceive to be alarm symptoms differs from perceptions of healthcare professionals. It was also highlighted that there was a discrepancy in the patient interval found in this study with a previous study, with this study showing 35 days as the median patient interval, compared to a primary care audit conducted by Lyratzopoulos and colleagues (2015) which showed a patient interval of 19 days. It was also interesting that family history of cancer was associated with a longer HSI, given that family history is a risk factor for cancer.

The main advantage of this study is the prospective design, with the recruitment of patients prior to their diagnosis. Patients reported their symptoms and so provided insight into what they experienced, but the group did acknowledge that this was retrospective as symptoms were those experienced before they presented at the GP, with these being up to 2 years before diagnosis. The group felt the authors’ use of multiple regression models was a benefit to the study, allowing an investigation into time-constant and duration-varying effects, as in line with previous research, it was shown that rectal bleeding becomes normalised over time.

We discussed limitations of the study and recognised that the authors did not acknowledge the Be Clear on Cancer Awareness Campaigns which took place during the data collection (Jan-March 2011, Jan-March 2012, Aug-Sept 2012) and could have had an impact by shortening patient interval and increasing referral rates. We also discussed that there could be an inherent bias in GPs and that HSI could be due to this bias of GP’s wanting to reassure patients that their symptom is likely to be the sign of something other than cancer. This could also help explain the longer time to diagnosis and HSI in those with depression and anxiety, as GP’s may feel the need to over reassure these patients, recognising that they are already anxious. However, when symptoms have been shown to be a ‘false alarm’, overreassurance and undersupport from healthcare professionals has been shown to lead patients to interpret subsequent symptoms as benign and express concern about appearing hypochondriacal (Renzi, Whitaker and Wardle, 2015). It may also be due to healthcare professionals attributing symptoms to some of the side effects related to medication for depression and anxiety such as diarrhoea, vomiting, and constipation. The authors suggest also that healthcare professionals might not take these patients physical symptoms seriously. There was also a small number of CRC patients given the amount of patients approached, with the authors recognising the study is underpowered. There may also have been an overestimate of the number of bowel symptoms in non-cancer patients, which was recognised by the authors. It was also unclear that the authors had also conducted univariate analyses and that these were included in the supplementary material until they were mentioned at the end of the results.

There may also be differences in TDI depending on the type of referral e.g. two week wait, safety netting, and the group would have liked some more information about this. The group would also have liked to see some discussion about the median HSI being longer (58 days) than the 31 days currently recommended for diagnosis from the day of referral and the new target for 2020 of 28 days from referral to diagnosis. It would have also been useful to have some information about how many consultations patients had before being referred, as the authors state in the introduction that 1/3 of CRC patients have three or more consultations with the GP before a referral is made. It would also have been informative for the data on how long participants took to return their questionnaire, with the authors stating that most were completed within 2 weeks, but that some were within 3 months.

It would be interesting to look further into the factors affecting patients presenting to their GP straight away with symptoms and those which delay. We discussed possible explanations being personality, extreme individual differences in how symptoms are perceived as serious or not and external factors such as being too busy. It would also be interesting to consider whether these symptoms were mentioned by patients as an afterthought at the end of a consultation about something else, or whether this was the symptom that patients primarily presented to the doctor with.

In conclusion, the HBRC group read the article with great interest and would encourage further studies in this area.

Conflicts of interest: We report no conflict of interests and note that the comments produced by the group are collective and not the opinion of any one individual.

References

1) Lyratzopoulos G, Saunders CL, Abel GA, McPhail S, Neal RD, Wardle J, Rubin GP (2015) The relative length of the patient and the primary care interval in patients with 28 common and rarer cancers. Br J Cancer 112(Suppl 1): S35–S40.

2) Renzi C, Whitaker KL, Wardle J. (2015) Over-reassurance and undersupport after a 'false alarm': a systematic review of the impact on subsequent cancer symptom attribution and help seeking. BMJ Open. 5(2):e007002. doi: 10.1136/bmjopen-2014-007002.

On 2017 Feb 03, Alfonso Leiva commented:

I would like to remark this study is the first prospective cohort to analyse the assotiation between time to diagnosis and stage. Fiona Walter et al studied the factors related to longer time to diagnosis and tried to explain the lack of assotiation between longer time to diagnosis and stage. We have recently published an article to explain this paradox and suggest confounding by an unknown factor as a posible explination. We have suggested the stage when symptoms appear is the main confounder in the assotiation between time to diagnosis and stage of diagnosis and propose a graphic representation for the progression of CRC fron an preclinical asymtomatic stage to a clinical symptomatic stage.

Leiva A, Esteva M, Llobera J, Macià F, Pita-Fernández S, González-Luján L, Sánchez-Calavera MA, Ramos M. Time to diagnosis and stage of symptomatic colorectal cancer determined by three different sources of information: A population based retrospective study. Cancer Epidemiol. 2017 Jan 23;47:48-55.