Primary-care Dilemma: Diagnosing Ovarian Cancer at an Early Stage
Primary-care Dilemma: Diagnosing Ovarian Cancer at an Early Stage
Abstract & Commentary
By William B. Ershler, MD
Synopsis: Symptoms of ovarian cancer are often non-specific and commonly encountered in the community. In this case-control, retrospective review conducted in a primary care setting, seven symptoms were shown to have predictive value, often up to a year prior to diagnosis. The data may prove useful to physicians deciding when to pursue a diagnosis of ovarian cancer and to panels developing consensus statements on ovarian cancer diagnosis.
Source: Hamilton W, et al. Risk of ovarian cancer in women with symptoms in primary care: population based case-control study. BMJ. 2009;339:2998-3005.
Ovarian cancer represents the sixth most commonly diagnosed cancer among women in the world and causes more deaths per year than any other cancer of the female reproductive system.1 In fact, ovarian cancer has the worst prognosis of all gynecological cancers, with an overall five-year survival of about 35%.2 Yet, when diagnosed early (stage I or II), survival is 80%-90%, compared with 25% when diagnosed at later stages (III and IV).3 Currently, only 30% of patients are diagnosed in these early stages.4 Inasmuch as no effective screening test has been developed,5 the main prospect for early detection is the identification of the disease at the onset of symptoms. Unfortunately, these are often fairly common and non-specific. Of these, most common are abdominal pain, abdominal distension, pelvic pain, increased urinary frequency, constipation or diarrhea, abnormal vaginal bleeding, weight loss, abdominal bloating, and fatigue. Unfortunately, these symptoms are also common in non-malignant conditions. In fact, in one study, 95% of women visiting a primary care physician had at least one symptom potentially representing ovarian cancer.6
The goal of the current research was to assess the positive predictive value (PPV) of selected symptoms reported to primary care physicians with regard to the presence of ovarian cancer. In this context, the PPV is the chance that a woman with a symptom actually has ovarian cancer; this could be useful for the practitioner to determine the extent to which this diagnosis should be sought.
To this end, Hamilton et al conducted a case-control, retrospective review of 39 primary care practices in Devon, England. The study was designed to be large enough to calculate PPVs for ovarian cancer for all important symptoms encountered in primary care, both individually and in combination.
The investigators coded each subjects' primary-care record for one year before the diagnosis of ovarian cancer. There were 212 women aged < 40 with a diagnosis of primary ovarian cancer in the years 2000 through 2007, and for each patient,5 age and practice site (total =1060) controls were enrolled. The main outcome measures were odds-ratios (ORs) and PPVs for symptoms from conditional logistic regression analyses.
Seven symptoms were associated with ovarian cancer in multivariable analysis. See Table below for the univariable positive predictive values and multivariable odds-ratios (with 95% confidence intervals) for these seven symptoms.
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In 181 (85%) cases and 164 (15%) controls, at least one of these seven symptoms was reported to their practitioner in the year prior to diagnosis. After exclusion of symptoms reported in the 180 days before diagnosis, abdominal distension, urinary frequency, and abdominal pain remained independently associated with a diagnosis of ovarian cancer.
Commentary
This study, conducted in a primary-care setting, is very instructive in that it reveals that early ovarian cancer is not as asymptomatic as initially thought. In fact, women with ovarian cancer usually report symptoms often several months before diagnosis. The problem, of course, is that these are often non-specific and, if extensive work-up is undertaken with the occurrence of a single symptom, exhaustive testing might be undertaken to the benefit of only a few. Once again, it falls upon the primary-care provider to exercise clinical judgment in proceeding with the work-up. Short of a breakthrough in the development of a more precise screening instrument, the development of consensus recommendations, based upon the findings provided, would seem a reasonable next step.
With regard to new screening instruments for ovarian cancer, several recent proteomics-based biomarker discovery projects show promise for the development of highly sensitive and specific markers for gynecological malignancies, including ovarian cancer.7 Such would be a remarkable advance for this difficult problem.
References
1. Permuth-Wey J, Sellers TA. Epidemiology of ovarian cancer. Methods Mol Biol. 2009;472:413-437.
2. Berrino F, et al. Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995-99: results of the EUROCARE-4 study. Lancet Oncol. 2007;8:773-783.
3. Colombo N, et al. Ovarian cancer. Crit Rev Oncol Hematol. 2006;60:159-179.
4. Quaye L, et al. The effects of common genetic variants in oncogenes on ovarian cancer survival. Clin Cancer Res. 2008;14:5833-5839.
5. Rufford BD, et al. Feasibility of screening for ovarian cancer using symptoms as selection criteria. BJOG. 2007;114:59-64.
6. Goff BA, et al. Frequency of symptoms of ovarian cancer in women presenting to primary care clinics. JAMA. 2004;291:2705-2712.
7. Nossov V, et al. The early detection of ovarian cancer: from traditional methods to proteomics. Can we really do better than serum CA-125? Am J Obstet Gynecol. 2008;199:215-223.
Symptoms of ovarian cancer are often non-specific and commonly encountered in the community. In this case-control, retrospective review conducted in a primary care setting, seven symptoms were shown to have predictive value, often up to a year prior to diagnosis.Subscribe Now for Access
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