Cancer biology may be more important than diagnostic delay

Editor—Delay in the diagnosis of cancer is universally considered to be unacceptable. The results of the study of treatment delay and survival in women with endometrial cancer in Scotland are therefore counterintuitive.¹ Crawford et al found that delay and survival were inversely related. Women with the shortest delay had more advanced disease and had the worst survival. Although these results were unexpected, they are consistent with previous studies in cervix and breast cancer.

An earlier study in the west of Scotland found no association between the duration of symptoms and the stage at presentation of 146 patients with cervical cancer.² Tumour proliferation rates were evaluated after in vivo labelling with the DNA precursor BrdUrd. Patients with increasing tumour stage tended to have more rapidly proliferating tumours with a higher mean labelling index (P=0.001) and a shorter mean potential doubling time (P=0.023). The results imply that in most cases, stage at diagnosis is affected more by the biology of the cancer than by diagnostic delay.

The basis of screening for breast cancer is that mammographic screening advances the diagnosis by more than a year, distant metastases being less likely. Evidence on the role of diagnostic delay is, however, conflicting. Richards et al in a large systematic review of 87 studies found that delays of three to six months were associated with poorer survival.³ In contrast, a study from Yorkshire found no evidence of an adverse prognostic effect of provider delay longer than 90 days.⁴

Diagnostic difficulties may explain these apparent contradictory findings. The classic presenting symptom of endometrial cancer is vaginal bleeding. Rapidly proliferating tumours tend to be more friable and have poorer vasculature and may present with heavy vaginal bleeding suggestive of cancer. By contrast, slow growing, less well differentiated tumours may present initially with occasional slight vaginal bleeds that may be ascribed initially to more innocent causes such as atrophic change.

Diagnostic difficulties also may account for the survival paradox in breast cancer. Rapidly growing lumps may suggest cancer to both doctors and patients. On the other hand, the diagnosis of cancer may be less obvious in slow growing lumps, especially small lesions that are difficult to detect.

The conclusion to be drawn from these studies is that, although diagnostic delay is highly undesirable, in most cases the biological phenotype of the tumour is probably more important than a short diagnostic delay in determining ultimate outcome.