For which cancers might patients benefit most from expedited symptomatic diagnosis? Construction of a ranking order by a modified Delphi technique

Mortality benefits

Summary of the main findings

This is the first study to try to rank cancers by potential mortality benefit from expedited symptomatic diagnosis. The final ranking, although not definitive, suggests that cancers with the greatest potential benefit are breast, uterus and melanoma; in contrast, pancreas and brain were considered to have the least potential benefit. The Likert responses for whether mortality gains were to be expected from expediting symptomatic diagnosis were concordant with the final rankings. Perceived morbidity benefits were largely unrelated to the mortality ranking for cancer sites.

Strengths and limitations

This study had two distinct phases: construction of the initial ranking and the Delphi process. Both have methodological limitations. The initial Column A₁ was predicated upon the view that European cancer survival differences reflected differences in timeliness of diagnosis in part at least. We used the best information available, and considered it preferable to provide an initial ranking rather than offering Delphi participants a starting point of all cancers being equal – while accepting the possibility of an ‘anchoring’ effect [20]. This effect occurs when people are given a specific value for a quantity, before measuring (or in our case, adjusting) the quantity itself. The Abdel-Rahman paper uses data which is now close to twenty years old; although improvements in diagnosis and treatment may have changed the ranking somewhat, the purpose of the initial ranking was to provide a reasonable starting point based – in part at least – on diagnostic differences. More recent data – had it been available – would have reflected the improvements in UK cancer diagnostic pathways in recent years, making international variation less helpful in showing up any effect from improved diagnostics.

The adjustment for survival was also debatable; the rationale was that patients with cancers with high cure rates could still benefit from expedited diagnosis. One internal finding suggests that this process was valuable: the positive correlation between the change in scores introduced by the survival adjustment and the change in scores from the Delphi exercise. In short, the Delphi exercise moved in the same direction as the survival adjustment, rather than reversing it. Furthermore, there was ample latitude in the Delphi exercise to change any misplaced cancer. A cancer ranked last could have become first, and vice versa, though no cancer changed ranking as dramatically as this. Other choices in Phase 1, including different weightings, would have generated different starting points for the Delphi participants; they might not have led to important differences in the final outputs. One unfortunate effect of the survival adjustment was that oral cancer was lost to the Delphi process, as we could not find appropriate survival figures. The initial position of oral cancer was mid-ranking, between rectal cancer and non-Hodgkin lymphoma. We cannot know what its final position would have been had it entered the Delphi exercise.

The Delphi exercise had two rounds. A feature of the Delphi process is reiteration, with structured feedback and subsequent rounds helping to develop consensus. The number of rounds is a balance between maintaining recruitment and allowing change. We saw little alteration in Round 2 – with nearly a third of the panel suggesting no change at all was needed – and hence the value of a third round would probably have been limited. Our number of Delphi participants was within the usual range [21]; of 189 invited, 22 took part, all of whom completed both rounds. We do not know why most of the non-responders declined. The evidence pack was large, and many participants indicated that the exercise required both considerable time and intellectual engagement. We cannot know if a different panel would have yielded different results. Deliberately, we excluded patients and surgical specialists from the Delphi process: both groups largely have expertise in a single cancer site (or grouped sites, such as urological cancers). We believed that the Delphi participants should be able to comment across a wide range of cancers to allow them to adjust the rankings appropriately. A future exercise could extend to a much wider community, including patients, the public and specialists.

The findings from this study would change if major improvements in treatment for a particular cancer were available. For example, were a new drug for pancreatic cancer to be developed, then expedited symptomatic diagnosis of pancreatic cancer would presumably increase in importance. Therefore, our rankings are of value only for the present time. They also only pertain to the 21 cancers we included. Omission of other cancers from the ranking does not mean no benefit is to be expected, just that any such benefit is unreported.

Interpretation

This is the first exercise of this nature that we know of. Thus we cannot directly compare it with other published studies. The research question offered to Delphi participants made no reference to division of the pre-diagnostic period into patient intervals (before entry into healthcare) and healthcare provider/system intervals [22]. Thus the results may pertain to both, and hence have possible relevance to either awareness campaigns or the design of diagnostic services.

The findings on the potential morbidity benefit were unexpected. Although no cancer sites attracted a median response of ‘disagree’ or ‘strongly disagree,’ ten had a median response of ‘undecided’. This was despite the emphasis given to the possibility of palliation and symptom relief. Three of these cancer sites – breast, melanoma and prostate – have a sizeable literature relating to over-diagnosis, though this mostly relates to screen-detected cancer. It is plausible that, for these sites, Delphi participants believed that the morbidity benefits were outweighed by harms, though it is hard to see how this could extend to the other seven cancers.

Three cancers – breast, uterus and melanoma – were ranked as being most likely to result in improved mortality outcomes through expedited symptomatic diagnosis, and there was a moderate gap between these cancer sites and the next group. In the UK, diagnostic services for breast cancer are highly streamlined, such that in the English National Health Service women with almost any breast complaint (other than pain) are assessed rapidly for the possibility of cancer. This facility – which is the most comprehensive of all the various cancer diagnostic services – is consonant with our findings. We cannot know if the presence of such a scheme influenced Delphi participants, who could reasonably have inferred from the existence of such a service that it was particularly warranted. The generally accepted benefits of breast cancer screening may have encouraged Delphi participants to consider breast to be particularly worthy of expedited diagnosis [23], even though the screening population is asymptomatic, and were not included in this study.

Uterine cancer has a similarity to breast cancer, in that a single presentation, post-menopausal bleeding, dominates [24]. Services for investigation of post-menopausal bleeding are also well-structured, and timely investigation is the norm. In contrast to breast cancer or melanoma, uterine cancer has not been considered for awareness campaigns encouraging women with post-menopausal bleeding to consult their doctors. Our results suggest this should be considered.

Melanoma also has a characteristic symptom, a pigmented lesion. Times to diagnosis are generally short, emergency admissions are rare, and few patients report seeing their doctor three or more times before diagnosis [7–9]. Some concerns about ‘over-diagnosis’ have been raised for melanoma [25], based on a stable number of deaths in the face of rising numbers of new diagnoses. An alternative interpretation is that good services for diagnosis of melanoma have led to improved survival, despite an increased incidence.

Sixteen cancers are ranked in the middle of the ranking, though for only one of them, prostate, did the Delphi respondents give a median Likert answer of ‘disagree’ to the statement that expedited symptomatic cancer diagnosis brought mortality benefits. Five cancers within this large grouping had large changes in the Delphi exercise: bladder and lung were promoted, and ovary, prostate and non-Hodgkin’s lymphoma fell. The promotion of bladder may represent the clear survival advantage of early bladder cancer diagnosis when compared with advanced disease. The promotion of lung cancer refutes some of the nihilism attaching to this subject; in the UK at the time of the Delphi exercise there was considerable public publicity of lung cancer symptoms, as part of the Be Clear On Cancer campaign. Furthermore, lung cancer resection rates are rising, and newer treatments, tailored to specific cancer genotypes, have entered mainstream practice. This circumstantial evidence may have encouraged Delphi participants to believe that expedited symptomatic diagnosis has benefits – for some lung cancer patients. Ovary is similar to bladder cancer in its sharp survival difference between early and advanced disease, though, in this cancer, advanced disease is the norm. Diagnostic testing has become much easier, with the widespread use of Ca125 [26]. It is hard to explain why non-Hodgkin’s lymphoma fell. Long-term results from a trial of surgery in prostate cancer have yielded small benefits, though with additional morbidity [27]. This is not the same as demonstrating benefits from expedited diagnosis. Furthermore, prostate screening trials have disappointed, reporting no, or very small benefits. This leaves a confusing picture, of small benefits at best – commensurate with its final place in the ranking.

Two cancers were deemed to be associated with the smallest gains from expedited diagnosis throughout the whole exercise: brain and pancreas. Both have very poor prognoses, and this may have been uppermost in Delphi participants’ minds [28]. Although expediting symptomatic diagnosis in these cancers may have less effect in improving survival compared with other cancers, it does not mean there is no value in trying to do so. The primary message is that we have to be realistic about what it is possible to achieve. A clear implication can be drawn: that research efforts should concentrate on other aspects, such as prevention, development of novel screening tools, including new biomarkers, and new targeted therapeutic agents. Quite rightly, these cancers with poor outcomes should receive preferential attention and funding, but that this should focus on areas most likely to offer tangible benefits.