Meta-Analysis: Long Delays in the Diagnostic Pathway to MM

Much greater efforts are needed to improve both the speed and accuracy of multiple myeloma (MM) diagnosis, according to a British study reported in BMJ Open. Constantinos Koshiaris, from Nuffield Department of Primary Care Health Sciences at University of Oxford, Oxford, UK, and colleagues conducted the first systematic review to quantify the entire diagnostic pathway for MM patients. They specifically looked at different intervals in each step of the pathway, and concluded that development of interventions that reduce the length of the diagnostic interval are warranted.

The researchers conducted a systematic review and meta-analysis that included searchers of the databases MEDLINE and Embase through January 2018. They excluded articles focusing on children or adolescents and on the asymptomatic form of the disease (monoclonal gammopathies and smoldering myeloma).

Koshiaris et al identified nine studies that were appropriate to evaluate; they found that in two studies with 465 patients, the patient interval (first symptom to first presentation) was a median of 26.3 days (interquartile range [IQR], 1–98). In two studies with 326 patients the primary care interval (first presentation to first referral), was a median of 21.6 days (IQR, 4.6–55.8). 

The study showed that the diagnostic interval (first presentation to diagnosis) was a median of 108.6 days (IQR, 33.3–241.7) based on seven studies with 5,395 patients. One study (N = 341) showed the time-to-diagnosis (first symptom to diagnosis) interval was 163 days (IQR, 84–306).

The review overall found that many MM patients experience a diagnostic interval longer than 3 months until diagnosis is confirmed, and several factors may account for this. Myeloma primarily affects older adults, and 59% of patients are diagnosed after age 70. Myeloma symptoms such as back pain, fatigue, and repeated infections can easily be attributed to a variety of nonmalignant potential causes.

The authors note that, consequently, myeloma is one of the most difficult cancers to discern in primary care, given that symptoms of the disease are so similar to other common ailments, and nonspecific. They explain that the fact that no effective screening program for myeloma is available may be due to potential benefits being outweighed by the potential costs, including the risk of many people having to undergo a battery of possibly unnecessary tests, as well as potential overdiagnosis of monoclonal gammopathy of undetermined significance, or MGUS.

However, they point out that the growing clinical use of genomics and the increasing use of artificial intelligence in medicine may make it possible to address this problem in novel ways. Koshiaris and colleagues suggest there is a clear need to design new interventions that shorten diagnostic intervals, which they found in some cases could exceed 8 months. Meaningful reductions in the time to diagnosis, they said, could improve patient outcomes.