Women with ovarian cancer (OC) who seek help for symptoms early on may perversely have worse survival than those who go to doctors later due to difficulties in identifying the disease and a “wait time paradox” that masks the benefits of early diagnosis.
The findings, in JAMA Network Open, counter earlier research that has suggested there are minimal benefits associated with shortening the time between symptom presentation and diagnosis.
Rather, the current study indicates that traditional linear approaches linking diagnostic timing and mortality obscure the impact that disease severity has on this association.
Specifically, these linear modeling approaches may obscure the impact of the “wait time paradox” which holds that patients with more severe symptoms are diagnosed more quickly but have poorer survival.
The research also reveals the unique difficulties of identifying ovarian cancer—a disease that can be mistaken for several other gastrointestinal conditions.
In a Commentary article accompanying the research, Dana Chase, MD, and Luke Abdel-Sayed, a third year psychobiology student, both from UCLA, said the study highlights the fact that subtle symptoms of ovarian cancer can be under recognized.
“This calls for a push toward enhanced education among physicians treating postmenopausal women,” they maintained.
“Many symptoms of OC might be confused with other diseases, including irritable bowel syndrome, gastroesophageal reflux disease, weight gain, diverticular disease, ulcers, and constipation.
“Recognizing the presence of OC in patients with symptoms overlapping with typical gastrointestinal symptoms could in turn lessen diagnostic delay.”
A team led by Caroline Thompson, PhD, from the University of North Carolina at Chapel Hill, analyzed diagnostic intervals and survival among 2359 adult women in their U.S. state with symptomatic epithelial ovarian cancer over a 10-year period.
The diagnostic interval was defined as the time between the first symptom-related health care encounter and the time of diagnosis. The team used nonlinear methods to characterize confounding by severity.
The investigators identified a U-shaped curve between the length of the diagnostic interval and survival, with better outcomes among women diagnosed within intermediate intervals and worse outcomes among those diagnosed at both shortest and longest diagnostic intervals.
Those who were diagnosed the fastest had the highest number of advanced stage patients.
The median diagnostic interval was 33 days and ranged from 10 to 149, while the mean was 88 days. Diagnostic intervals ranged from zero to 365 days.
Women who initially presented with abdominal or pelvic symptoms had the shortest mean intervals, with corresponding intervals of 81 days and 57 days. Those presenting with gastrointestinal symptoms had the longest mean intervals, at 105 days.
Women who had longer diagnostic intervals often visited multiple healthcare professionals before being diagnosed with ovarian cancer. Those with a single clinical encounter prior to a diagnosis were in the grouping with the shortest interval quartile.
Study participants in the second-shortest diagnostic interval had the best outcomes and were more likely than others to be non-Hispanic White and younger, as well as living in less socioeconomically deprived areas.
“Patients with shorter diagnostic intervals tend to have worse survival outcomes, which is most likely because patients with higher severity symptoms are diagnosed more quickly,” summarized Chase and Abdel-Sayed.
“Patients with longer diagnostic intervals are more likely to present with nonspecific gastrointestinal symptoms, often experience multiple clinical encounters before diagnosis of OC, and would most likely benefit from earlier diagnosis.
“Patients with intermediate diagnostic intervals had the best outcomes and were diagnosed relatively early, without severe symptoms.”
Thompson and co-workers added: “Prior studies reporting no association between diagnostic timeliness and survival may reflect methodologic limitations rather than biological reality.
“Larger studies using nuanced analytical approaches, along with investment in clinical tools to improve diagnostic timing, may improve patient outcomes for this aggressive cancer.”
