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Menopause Live - IMS Updates
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Date of release: 25 July, 2011

Conventional ovarian cancer screening does not reduce its related mortality in postmenopausal women


Buys and colleagues [1] have recently reported the results of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial aimed at assessing the effect of screening for ovarian cancer on mortality. The studied population included 78,216 women aged 55–74 years who underwent either annual screening (n = 39,105) or conventional care (n = 39,111) at ten American centers between November 1993 and July 2001. The intervention group received annual screening with cancer antigen 125 (CA-125) measurements for 6 years and transvaginal ultrasound (TVU) for 4 years. The control group did not receive these screening measures. Median follow-up was 12.4 years analyzing for cancer diagnoses and death. Ovarian cancer rates were 5.7 and 4.7 per 10,000 person-years in the intervention group and control group, respectively. Ovarian cancer mortality rates were 3.1 and 2.6 per 10,000 person-years in the intervention group and control group, respectively. The authors concluded that the used screening protocol did not reduce ovarian cancer mortality as compared to conventional care (no TVU and CA-125 measurement).

Comment

During the last 20 years, the prevalence of advanced gynecological cancers including breast cancer has been reduced due to technical progress and screening protocols, allowing early detection of cancer and precancerous lesions and appropriate treatment. However, there have been no improvements in the early diagnosis and treatment of ovarian cancer. Thus, the mortality rate is still quite similar stage by stage to that during the last two decades. There have been a number of recent studies assessing the value of ultrasound examination and biochemical markers mostly CA-125 in the general population and in women with familial or hereditary predisposition [2,3]. Reports with small numbers and short follow-up intervals have continuously promoted the combined procedure despite borderline or negative results. The 18-year follow-up study by Buys and colleagues [1] is the first to report the effect of screening for ovarian cancer on mortality with an appropriate number of cases and controls, and sufficient follow-up. The PLCO Screening Trial demonstrated that combined TVU and CA-125 testing was ineffective for the early detection of ovarian cancer and avoidance of related death. Indeed, women annually screened and followed up for 13 years died from ovarian cancer in similar numbers to those who were not screened, and some results (e.g. mortality rate) were even worse in the intervention group. In addition, diagnostic follow-up of false-positive cases caused a number of complementary explorations and surgeries to be carried out and thus increased the number of related complications. Indeed, 3285 women had false-positive screening results; 1080 of them underwent surgery, of which 163 presented one or more serious complications. On the other hand, it is also important to mention that 72% of screen-detected cases were late stage (III and IV) ovarian cancers [4]. Anxiety, stress and emotional responses caused by complementary testing or other interventions due to incidental findings [5,6] should be taken into account as adverse effects of screening [5,6]. There are other publications derived from the PLCO Trial cohort concerning ovarian cancer that deserve to be commented on. It has been reported that, after 14 tests, the cumulative risk of having at least one false-positive was 48.8% [7] and the overall ratio of surgeries for screened vs. detected cancers was 19.5 : 1 [4]. These data illustrate the indirect effects of a low accurate protocol in terms of complementary explorations (surgery included), economic expenditures, and the negative emotional impact for women. It is important to bear in mind that excessive screening and interventions are undertaken due to the fear of cancer development. Pathological findings after false-positive screening tests have been reported in the PLCO Trial [8]. In this study, serous cystadenoma was the most frequent tumor and women with a false-positive TVU testing were younger, heavier and with higher previous hysterectomy rates [8]. A second aspect to be considered is that volunteers for screening programs are generally healthier with lower mortality risk than the general population. This includes mortality rates unrelated to cancer [9]. We have previously emphasized the need for new approaches, mostly based on biochemical markers, that may identify ovarian cancer antigens precisely [10]. In this sense, we hope proteomic analysis will be useful in detecting ovarian cancer. Several features of ovarian cancer do not allow for a simple, easy, and cost-effective screening approach. Symptoms are too vague, prevalence is low, tumor markers have low specificity, and, in many cases, early abdominal dissemination ensues without significant adnexal tumor growth [10,11]. Finally, the assessment of any screening protocol should include false-negative and false-positive rates and the ways in which to manage these groups of patients, complementary diagnostic interventions, the economic cost and the psychosomatic sequelae of incidental diagnosis unrelated to the target goal of early cancer diagnosis and treatment.

Comentario

Faustino R. Prez-Lpez
Department of Obstetrics and Gynecology, University of Zaragoza, Zaragoza, Spain

Peter Chedraui
Institute of Biomedicine, Universidad Catlica de Santiago de Guayaquil, Guayaquil, Ecuador

    References

  1. Buys SS, Partridge E, Black A, et al.; PLCO Project Team. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 2011;305:2295-303.
    http://www.ncbi.nlm.nih.gov/pubmed/21642681

  2. Bosse K, Rhiem K, Wappenschmidt B, et al. Screening for ovarian cancer by transvaginal ultrasound and serum CA125 measurement in women with a familial predisposition: a prospective cohort study. Gynecol Oncol 2006;103:1077-82.
    http://www.ncbi.nlm.nih.gov/pubmed/16904167

  3. Menon U, Gentry-Maharaj A, Hallett R, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 2009;10:327-40.
    http://www.ncbi.nlm.nih.gov/pubmed/19282241

  4. Partridge E, Kreimer AR, Greenlee RT, et al.; PLCO Project Team. Results from four rounds of ovarian cancer screening in a randomized trial. Obstet Gynecol 2009;113:775-82.
    http://www.ncbi.nlm.nih.gov/pubmed/19305319

  5. Sukegawa A, Miyagi E, Asai-Sato M, et al. Anxiety and prevalence of psychiatric disorders among patients awaiting surgery for suspected ovarian cancer. J Obstet Gynaecol Res 2008;34:543-51.
    http://www.ncbi.nlm.nih.gov/pubmed/18937707

  6. Gonalves V, Jayson G, Tarrier N. A longitudinal investigation of psychological disorders in patients prior and subsequent to a diagnosis of ovarian cancer. J Clin Psychol Med Settings 2010;17:167-73.
    http://www.ncbi.nlm.nih.gov/pubmed/20490630

  7. Croswell JM, Kramer BS, Kreimer AR, et al. Cumulative incidence of false-positive results in repeated, multimodal cancer screening. Ann Fam Med 2009;7:212-22.
    http://www.ncbi.nlm.nih.gov/pubmed/19433838

  8. Nyante SJ, Black A, Kreimer AR, et al. Pathologic findings following false-positive screening tests for ovarian cancer in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. Gynecol Oncol 2011;120:474-9.
    http://www.ncbi.nlm.nih.gov/pubmed/21144559

  9. Pinsky PF, Miller A, Kramer BS, et al. Evidence of a healthy volunteer effect in the prostate, lung, colorectal, and ovarian cancer screening trial. Am J Epidemiol 2007;165:874-81.
    http://www.ncbi.nlm.nih.gov/pubmed/17244633

  10. Prez-Lpez FR, Chedraui P, Troyano-Luque JM. Peri- and post-menopausal incidental adnexal masses and the risk of sporadic ovarian malignancy: new insights and clinical management. Gynecol Endocrinol 2010;26:631-43.
    http://www.ncbi.nlm.nih.gov/pubmed/20500106

  11. Moore LE, Pfeiffer RM, Zhang Z, Lu KH, Fung ET, Bast RC Jr. Proteomic biomarkers in combination with CA 125 for detection of epithelial ovarian cancer using prediagnostic serum samples from the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. Cancer 2011; June 29. doi: 10.1002/cncr.26241.
    http://www.ncbi.nlm.nih.gov/pubmed/21717433