Diagnose technieken: een nieuwe bloedtest plus ultrasound bij verdenking van eierstokkanker lijkt betrouwbaar en kan veel vrouwen eerder genezende behandeling geven. Artikel update 25 mei 2010

22 mei 2010: Bron: Medscape en J Clin Oncol 28:7s, 2010

Een nieuwe aanpak van screening op eierstokkanker lijkt nabij voor vrouwen met een zeker risico op eierstokkanker te ontwikkelen. Het toepassen van een bloedtest gebaseerd op een algoritme van de CA 125 waarden , de zogeheten Algorithm (ROCA), die is gebaseerd op leeftijd van de patiënt en de trends in de CA-125 bloedwaarden, bleek zeer weinig valse positieven te geven en had een betrouwbaarheid van 99,9%.

Hoewel twee grensgevallen niet werden gedetecteerd door het ROCA, werden geen gevallen van invasieve kanker van de eierstokken gemist, zegt studieleider Karen Lu, MD, hoogleraar gynaecologische oncologie aan de Universiteit van Texas MD Anderson Cancer Center in Houston.

"Het mooie van het algoritme is dat elke individuele vrouw uiteindelijk haar eigen uitgangssituatie kan vaststellen, gebaseerd op haar eerdere CA-125 waarden," zei ze.

Het doel van de studie was om de specificiteit en positief voorspellende waarde van een 2-stap-strategie voor nog gezonde postmenopauzale vrouwen te beoordelen, om nauwkeuriger het risico op eierstokkanker in te schatten. Een deel van de strategie is een verwijzing van de vrouw met hoge scores op de ROCA naar een transvaginale echografie (TVS) en een klinische evaluatie met een gynaecologisch oncoloog.

In deze prospectieve studie single-groep, namen 3238 postmenopauzale vrouwen van 50 tot 74 jaar deel en werden 9 jaar gevolgd. Geen van de deelnemers had een significante familiegeschiedenis van borst-of eierstokkanker. In de studie werden een aantal vrouwen vroegtijdig verwezen naar een oncoloog en konden zo veel eerder en ook effectiever geholpen worden aan hun beginnende eierstokkanker. Er bleken geen missers bij te zitten gedurende de looptijd van de studie.

Het ROCA biedt 3 mogelijke routes. Vrouwen met een laag risico hoeven slechts 1 keer per jaar terug te keren voor een jaarlijks CA-125 bloedonderzoek, voor vrouwen met een gemiddeld risico wordt hun CA-125 test herhaald elke 3 maanden, en de vrouwen met een hoog risico zullen worden verwezen voor een TVS en klinische evaluatie. Opmerkeljk, een arts vertelde mij jaren gelden dat je zelf kunt vastellen of je risico mhebt op kanker. Als je dire weken lang 4 keer per dag om de 6 uur je temperatuur meet en darvan een grafiek maakt ontstaat er een bioritme. Wie een bioritme heft met min of meer verschil in laagste tempetratuur en hoogste temperatuur van 0,4 tot 0,8 graden heeft een normaal bioritme en heeft waarschijnlijk geen kankner. Wie echter een bioritme heeft met minimale verschillen in temperatuurhoogtes dus minder dan 0,4 graad tussen hoogste en laagste dagelijks zou lacverstandig aan doen naar de huisarts te gaan als er ook nog bijkomende klachten zijn. De neiwue eierstokkankertest ljikt hier wle wat op zo te lezen.

Lees verder hieronder het abstract van de studie

Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr 5003)

Abstract No: 5003

Author(s): K. H. Lu, S. Skates, T. B. Bevers, W. Newland, R. G. Moore, L. Leeds, S. Harris, O. W. Adeyinka, H. A. Fritsche, R. C. Bast; University of Texas M. D. Anderson Cancer Center, Houston, TX; Massachusetts General Hospital, Boston, MA; Iowa Clinic, Des Moines, IA; Women and Infants Hospital, Providence, RI; Obstetrical and Gynecological Associates, Houston, TX; Baylor Sammons Breast Center, Dallas, TX; University of Texas Health Science Center, Houston, TX

A prospective U.S. ovarian cancer screening study using the risk of ovarian cancer algorithm (ROCA).

Sub-category: Ovarian Cancer

Category: Gynecologic Cancer

Meeting: 2010 ASCO Annual Meeting

Citation: J Clin Oncol 28:7s, 2010 (suppl; abstr 5003)

Abstract No: 5003

Abstract:

Background: There are currently no effective screening tools for the early detection of ovarian cancer in women at average population risk. We evaluated a screening strategy that incorporates change of CA-125 over time and age of the participant to estimate risk of ovarian cancer, referring a small fraction (~2%) of apparently healthy individuals annually to transvaginal sonography (TVS).

Methods: A single arm, prospective, multicenter screening study enrolled postmenopausal women age 50 to 74 with no significant family history of breast or ovarian cancer. Participants underwent a CA-125 blood test annually. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to the next annual CA-125 (low risk), repeat CA-125 in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). Based on clinical findings and TVS, the gyn onc made the decision whether to proceed with surgery.

Results: 3238 women participated over an eight year period. The average annual rate of referral to 3 monthly CA125 was 6.8%, and the average annual rate of TVS and gyn onc referral was 0.9%. Cumulatively 85 women (2.6%) received TVS and referral to a gyn onc. Eight women subsequently underwent surgery based on the TVS and referral, with 3 invasive ovarian cancers, 2 borderline ovarian tumors and 3 benign ovarian tumors, providing a positive predictive value of 37.5% (95% CI 8.5%,75.5%).The combined specificity of ROCA followed by TVS for referral to surgery is 99.7% (95% CI 99.5%, 99.9%). The 3 invasive ovarian cancers were high-grade epithelial tumors that were all early stage (two stage 1C and stage IIB). All 3 women with invasive ovarian cancer had at least 3 years with low risk, annual CA-125 values prior to a rising CA-125.

Conclusions: In this prospective, single arm study, the ROCA followed by TVS demonstrated excellent specificity and PPV in a population of U.S. women at average risk for ovarian cancer. As expected, less than 1% of participants annually required a TVS. In addition, the invasive high-grade ovarian cancers that were detected were early stage. This study provides early evidence that ROCA followed by TVS is a feasible strategy for screening women over 50 years of age.

May 21, 2010 — A new approach to ovarian cancer screening appears feasible and effective for women at average risk of developing the disease. The Risk of Ovarian Cancer Algorithm (ROCA), which is based on patient age and trends in CA-125 blood testing, demonstrated very few false positives and had a specificity of 99.9%.

Although 2 borderline cases were not detected by the ROCA, no cases of invasive ovarian cancer were missed, explained lead author Karen Lu, MD, professor of gynecologic oncology at the University of Texas M.D. Anderson Cancer Center in Houston.

Dr. Lu reported her findings during a presscast that previewed several presentations from the forthcoming American Society of Clinical Oncology (ASCO) 46th Annual Meeting. These data will be presented on June 6.

"The beauty of the algorithm is that each individual woman ultimately established her own baseline, based on her prior CA-125 values," she said.

The incidence of ovarian cancer in postmenopausal women is 1 in 2500; it is the most lethal gynecologic cancer. Unfortunately, more than 75% of cases present with advanced-stage disease, when cure rates are less than 30%, explained Dr. Lu.

If a diagnosis is made at an early stage, then outcomes are generally much better, with reported cure rates of 60% to 90%. "But currently, there are no effective screening methods," Dr. Lu pointed out during her talk.

The purpose of the study was to assess the specificity and positive predictive value of a 2-step screening strategy for healthy postmenopausal women, which incorporated changes in CA-125 over time and age of the participant, to more accurately estimate risk for ovarian cancer. Part of the strategy included referral of woman with high ROCA scores to transvaginal sonography (TVS) and to a clinical evaluation with a gynecologic oncologist.

In this prospective single-group study, 3238 postmenopausal women from 50 to 74 years of age were enrolled over the course of 9 years. None of the participants had any significant family history of breast or ovarian cancer.

The ROCA offers 3 possible pathways, Dr. Lu explained. Women at low risk will return for an annual CA-125 blood screening, women at intermediate risk will have their CA-125 test repeated in 3 months, and women at high risk will be referred for TVS and clinical evaluation.

The majority of women (n = 2666; 86%) continued with annual CA-125 screening. "Over the 9-year period, only 2.6% of women were ever triaged to a transvaginal ultrasound," Dr. Lu said, "and 8 women underwent surgery."

The average annual rate of referral to 3 month CA-125 screenings was 6.8%; cumulatively, it was 15.4% (n = 501). The average annual rate of TVS and gynecologic oncologist referral was only 0.9%.

Of the 8 women who underwent study-directed surgery, 5 ovarian cancers were detected.

All 5 were diagnosed at an early stage, Dr. Lu noted. Of the 5 cancers, 3 were invasive disease and 2 were borderline ovarian tumors. The remaining 3 women who underwent surgery had benign lesions, although 1 was later diagnosed with endometrial cancer.

The 3 invasive ovarian cancers that were detected were all high-grade epithelial tumors, but at an early stage; 2 were stage 1C and 1 was stage IIB. The 3 women diagnosed with invasive disease all had low-risk annual CA-125 scores before their values rose.

In 2 of the cases of ovarian cancer, the CA-125 levels were normal and then rose abruptly after several years of screening, Dr. Lu explained. "In the third case, levels were low (in the 10 to 12 range), but in the fourth year of screening, they doubled to 22," she said. "The ROCA picked up that her baseline had doubled and that triggered her ultrasound and subsequent surgery."

Overall, the ROCA provided a positive predictive value of 37.5% (95% confidence interval . 8.5% - 75.5%). The combined specificity of ROCA followed by TVS for referral to surgery was 99.7% (95% CI, 99.5% - 99.9%).

Dr. Lu emphasized that "it is important to stress the clinical ramifications of the study; it is not practice changing at this time."

"We await the results of the definitive trial that examines mortality as an end point, which is currently ongoing in the United Kingdom," she added.

The large-scale study of the ROCA that is currently underway involves more than 200,000 women, and results are expected in 2015.

"The ROCA represents yet another example of personalized medicine," said Douglas W. Blayney, MD, president of ASCO. "Here we have it personalized toward a screening strategy. It also represents a more refined application of known technologies that are widely available."

Dr. Blayney reiterated that caution is needed before embracing this approach to screening. The relative rarity of this cancer was seen in this study, so it is very important that this strategy "not be adopted widely until a confirmatory study is done," he said.

Coauthor Herbert Fritsche reports receiving research funding from Roche Diagnostics. Coauthor Robert Bast reports serving in a consulted/advisory role for Fujiresio Diagnostics Inc.

American Society of Clinical Oncology (ASCO) 46th Annual Meeting: Abstract 5003. To be presented June 6, 2010.

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