This posting will be relatively long, but I wanted to share some excerpts from some of the research I've done on the CA-125 test, and explain what I've decided my next step will be.
I have one question for anyone here who may have knowledge about this area of testing, which I'll put in bold type below.
(If you are new to my story, my health background, the explanation about why this CA-125 test was an unintentional part of my recent bloodwork, and my reasons for not having seen a gynecologist immediately about these results are explained earlier in this thread.)
Main points:
1. I have a familial link to this kind of cancer.
My grandmother died in her mid-60s of endometrial cancer. I have now learned that endometrial cancer and ovarian cancer can be linked in some families. 10% of ovarian cancer has an identified familial link. Additionally, a high result on the CA-125 test can indicate endometrial cancer as well as ovarian cancer.
My female first cousin (sharing the same grandmother as above) had an ovarian tumor in her 30s and when they did surgery, they ended up doing a complete hysterectomy. At the present time, I do not know why that was.
My 23andme results say that I do not have the BRCA breast cancer genes that they screen for, but they only screen for, I think, 2 out of 150 of them.
2. My first test result of 314.9 is really high, and is a real cause for concern.
When non-malignant conditions (such as endometriosis, hepatitis, cirrhosis or benign tumors) give higher-than-normal results on the CA-125, those results are still usually below 65, and they are
almost always below 100 or 200.
98% of women, even pre-menopausal women, who have results above 53/65/100/200 are found to have a malignant condition - for the references on this, see below.
(I do realize that any particular test result can be due to a random fluke, an error, a mix-up, a labelling problem at the lab, a data-entry problem, etc.)
3. Even if a high result on this test is not due to cancer, almost all of the other conditions that a high result can indicate are noteworthy and probably need to be treated (see list of them below). A high result (across repeated CA-125 tests) is almost never due to something normal and minor that can be ignored.
4. The typical investigation into a high CA-125 result by a doctor is: repeat the CA-125 blood test one or more times, manual gynecological exam, ultrasound, CT scan, exploratory surgery. Only surgery and biopsy can be conclusive about whether there is ovarian cancer or not. The other tests may not be helpful in determining what the problem is exactly. Many doctors steer high-risk patients to exploratory surgery, just in case. There are complications from this surgery in 2 to 3% of patients, even if no cancer is found.
5. It has been shown in a large longitudinal study that early discovery and treatment of ovarian cancer surprisingly did not increase mortality figures or life expectancy overall. However, it caused increased worry and stress, healthcare expenditures, and medical procedures (including risky surgery). Thus, the recommendation is that this test not be used for screening of ovarian cancer in women who do not already have physical symptoms of such cancer, except in certain cases. (There is a new large trial going on in the UK now to look at the benefits of screening certain high-risk populations.)
6. If the CA-125 test is repeated and the result is higher the second time, this indicates that other medical investigations into the possiblity of cancer must be started. If the result is the same as before and there are no other symptoms of cancer, a series of tests can be done subsequently (like every 3 months - "watchful waiting"). If the result is lower than before, it might indicate that there was some kind of error with the first test, or that the health problem is not a malignant one, and again, a series of blood tests can be scheduled to keep an eye on it.
7. As my next step, I have decided to take the test (ordering it for myself from privatemdlabs.com) one more time. Having a second test immediately is probably what any MD would recommend doing, if I went to see a doctor first. I will do the test 6 weeks after the last test was done, in order to be at the opposite point in my menstrual cycle (this 6-week timing was recommended by Dr. Bast, the founder of the test, in one of the references I quote below). That blood draw will be 2 weeks from now.
After I get the results of the second test, I will have more information on which to base my decision about what to do after that.
8. Further information about my health, which has occurred to me may be relevant to the CA-125 result. Duh! (My last doctor was so blase about this, that I just kind of mentally filed it under "?")
Aside from the suspected endometriosis (first suspected by an MD when I was 21, but at that time I was too young for a laparoscopy so he told me to get one when I was married and preparing to have kids, which sadly has not occurred in my life) that I've had for my whole adult life, I have had some symptoms in the last few years that all is not well with my reproductive system -- I was diagnosed by my last doctor 2 years ago as having had an ovarian cyst that was twisted and probably popped (caused a lot of pain, doubling up on the floor, vomiting, lots of blood outflow, fever) -- but she based this only on my verbal description of what had happened to me (I was travelling when I had the 'attack' and I went to see her about it when I returned), and she did not do a physical exam, blood test, or anything. She said it was normal to have this happen.
In 2011 and the first half of 2012, the pain I had during my periods would make me vomit at the same time as blood was literally gushing out (sorry to be so frank), and this fun activity would go on for a couple of hours (I told that same doctor about this, and she was not concerned, even though I had iron deficiency which she attributed to the heavy period blood loss, and she was also not concerned about the iron deficiency).
Thankfully, for the past 12 months I have not vomited due to my periods, and the blood does not gush so much. My serum ferritin is now 51, as well.
9. I have tried to research the other tumor marker tests, to see if there might be others which could either confirm that something is putting out a cancer marker in my blood, or show that the problem might be originating in a different system in my body, like the liver or gut.
Because it was relatively inexpensive and worth a shot, this week I took a high-accuracy home pregnancy test to see if I might have hCG in my urine. I did not have any detectable hCG.
"Some diseases of the liver, cancers, and other medical conditions may produce elevated hCG and thus cause a false positive pregnancy test. These include choriocarcinoma and other germ cell tumors, IgA deficiencies, heterophile antibodies, enterocystoplasties, gestational trophoblastic diseases (GTD), and gestational trophoblastic neoplasms."
http://en.wikipedia.org/wiki/Pregnancy_test
My question to anyone who might know about these things: Are there any other tumor marker blood tests that I can order for myself which might provide some information about what is going on with my health? I am wondering especially about CA 15-3 and CA 19-9.
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Research
(My CA-125 level was 314.9)
Specific Numbers
This chart says that the CA-125 "level above which benign disease is unlikely" is 200 (in other words, a level over 200 is likely to indicate cancer).
http://www.aboutcancer.com/tumor_markers2.htm
In a study of 267 women, 31 had a CA-125 level over 100. Of those 31 women with a level over 100, 97% had cancer (30 women) and 3% (1 woman) had a nonmalignant problem.
http://www.questdiagnostics.com/testcenter/testguide.action?dc=TS_CA125
"In order to achieve a false-positive rate equivalent to that in post-menopausal women, i.e. 2%, the cut-off value for pre-menopausal women would be approximately 53 U/mL."
"Abnormal CA-125 is defined as >53U/mL in Premenopausal Women and >35U/mL in Postmenopausal Women."
http://www.ovariancancer.org/wp-content/uploads/2009/10/2009.11.04-Symptom-Diary-Guidance_FINAL.pdf
"A CA-125 above 65 in a 50-year-old or older woman is virtually diagnostic of malignancy with a specificity of 98%."
http://www.westcoastgynoncology.com/oc_refer.htm
"If a serum CA-125 level is raised in a premenopausal patient, but less than 200 units/mL, further investigation may be required to exclude or treat differential diagnoses. A level of more than 200 units/mL should prompt referral to a gynaecologist."
http://www.patient.co.uk/doctor/cancer-antigen-125-ca-125
"In cases of ovarian carcinoma, preoperatively determined values of CA 125 in serum are correlated with the extent of the expansion of the disease, histological type of tumor and degree of differentiation of malignant cells. Elevated values UP TO 65 U/mL in serum can also be found in other malignant minors (pancreas, breast, colon, bladder, lungs, liver) and in different benign diseases."
http://www.ncbi.nlm.nih.gov/pubmed/21053460
Of patients that turned out to have ovarian cancer, when their CA-125 was checked before their diagnosis, the "Patients with a Ca 125 level above 100 U/l had a significantly lower three-year survival rate. ...The tumor marker Ca 125 is a prognostic factor. Levels around 100 U/l are indicative of a bad prognosis."
http://www.ncbi.nlm.nih.gov/pubmed/17649781
"given the fact that the cutoff value was set in a way that excluded healthy individuals, any patient testing positive is likely to have a pathology that at a minimum would require diagnosis and in some cases, treatment. In those cases, the result of the test should be considered as beneficial for the patient, regardless of the specific pathology involved."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131516/
"Any condition that causes irritation to the peritoneum, fallopian tubes, ovaries or uterus can cause an elevated Ca-125. It is commonly elevated with endometriosis. I have seen values exceeding 2,000 u/ml in cirrhosis with ascites, pelvic infections and in one case of fallopian tube torsion."
http://www.gynoncology.com/ca-125/
"2% of premenopausal women without ovarian cancer will have levels exceeding 50 U/mL."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172691/
"In premenopausal women with symptoms, a slightly elevated CA 125 value may be misleading because elevated levels of CA 125 are associated with a variety of common benign conditions, including uterine leiomyomas, pelvic inflammatory disease, endometriosis, adenomyosis, pregnancy, and even menstruation. Nonetheless, extremely high levels of CA 125 may be useful in the evaluation of premenopausal women."
http://www.acog.org/Resources And P...y Detection of Epithelial Ovarian Cancer.aspx
Investigation
"If your CA 125 level is higher than normal, your doctor will likely repeat the test."
http://www.mayoclinic.com/health/ca-125-test/MY00590/DSECTION=results
"Abnormal tests were repeated after 4-6 weeks.
Persistently abnormal tests prompted a search for malignancy.
Tests that normalized on repeat were considered false positive."
http://www.ncbi.nlm.nih.gov/pubmed/12798709
"CA-125 is unreliable in differentiating benign from malignant ovarian masses in premenopausal women because of the increased rate of false positives and reduced specificity. This is because an elevated CA-125 level is also found in fibroids, endometriosis, adenomyosis and pelvic infection. When levels are elevated, serial monitoring can be helpful, as rapidly rising levels are more likely to be associated with malignancy than high levels which are static."
http://www.patient.co.uk/doctor/cancer-antigen-125-ca-125
"repeat CA-125 testing should be done at 6 weeks so that the patient, if pre-menopausal, will be at a different phase of the menstrual cycle."
"The CA-125 is repeated at six weeks if the first test is elevated and the ultrasound is normal. If the CA-125 level on the second test rises 50% or more from the baseline test, then repeat ultrasound is recommended. If the CA-125 value is stable, then the patient would follow the same path as if the first set of tests had normal CA-125 and ultrasound test results. If the CA-125 is rising but less than 50%, then a clinical decision is required, which may include returning in six additional weeks for another CA-125 test and/or repeat ultrasound."
"If either the TVS or the CA-125 is abnormal, or if both tests are abnormal, consultation with or
referral to a physician with advanced training and expertise in the management of ovarian cancer, such
as a gynecologic oncologist, is recommended."
"There are concerns about the costs of implementing these recommendations as well as the limited
capacity and access to high-quality TVS by sonographers experienced with evaluation of the ovaries for
non-obstetric purposes."
http://www.ovariancancer.org/wp-content/uploads/2009/10/2009.11.04-Symptom-Diary-Guidance_FINAL.pdf
"As with thyroid hormone, each individual has their own normal level for CA 125. Therefore changes in the individual's level are of more significance than the actual value.
An "abnormal" value must result in a search for the reason. At the very least this will involve a physical exam, an ultrasound, and if negative, a CT scan of the abdomen and pelvis."
http://www.usask.ca/cme/articles/ovarian/
"Three screening tests are currently employed: bimanual pelvic examination, cancer antigen (CA) 125, and transvaginal ultrasound."
"The pelvic examination does not add additional cost for women who are already undergoing regular gynecologic evaluation and is reliable when done by an experienced examiner, but it lacks adequate sensitivity and specificity as a screening test. It is estimated that physical examination detects only 1 in 10,000 ovarian carcinomas in asymptomatic women."
"Although the data from this trial provide reassurance that there is no apparent benefit to early detection and treatment of recurrence based upon intensive CA 125 surveillance, there may be specific subgroups of patients who might benefit."
"Ultrasound is not only expensive but also has limited specificity and sensitivity. In one published study, 4526 high-risk women underwent ultrasound every 6 months. There were 49 invasive surgical procedures: 37 for benign tumors and 12 for gynecologic malignancies. The detected malignancies were ovarian, peritoneal, or fallopian tube carcinoma in 10 women, all of which were stage III, and stage IA endometrial adenocarcinoma in 2 women. The authors concluded that ultrasound was of limited value for the detection of early stage EOC in asymptomatic high-risk women."
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3576854/
"Beginning in 1993, NCI launched PLCO, using an ovarian screening protocol that combined vaginal ultrasound with simultaneous CA-125 analysis, the latter pegged to a threshold of 35 IU/mL.
A total of 78,216 postmenopausal women, aged 55–74 years, were randomly assigned to either standard medical care or an intervention arm in which they were referred to their primary-care doctors if their ultrasound results were abnormal (enlarged or cyst-containing ovaries) or if their CA-125 levels were above the 35-IU/mL cutoff.
The protocol did not specify precisely how women and their doctors should respond to abnormal ultrasound or to elevated CA-125 levels. "Next steps could include repeat ultrasound, repeat CA-125, gynecological exam, or surgery," said Saundra Buys, M.D., a principal investigator in the PLCO trial and a director at the Huntsman Cancer Institute, at the University of Utah.
When the trial wrapped up after up to 13 years of observation, 212 women from the intervention arm and 176 women from the control group had been diagnosed with ovarian cancer. But ovarian cancer mortality differences between the two groups weren't statistically significant. A total of 118 deaths occurred in the intervention group, compared with 100 in the control group. According to Buys, that discrepancy probably reflects an "overdiagnosis bias" in the intervention arm. "Some of these cancers did not need to be diagnosed," she said. "They weren't going to cause death even if they weren't detected." That's because, as also occurs in prostate and breast tumors, some ovarian cancers are slow growing and might be better left untreated, explains Christine Berg, M.D., chief of the NCI's early detection research group. Moreover, CA-125 levels can rise in response to some benign conditions, including endometriosis, other ovarian diseases, and pregnancy. So, not only did PLCO's screening approach not reduce mortality in ovarian cancer, it also led to many surgeries performed to investigate positive screening results. Of 3,285 women with false-positive results, 1,080 underwent surgical follow-up, and among them, 163 women—15% in all—experienced at least one serious complication. "Some of those surgeries addressed other types of problems, so you can't always call them unnecessary," Buys said. "But we can say that screening the way we did it had no effect on survival, and it did result in surgeries for conditions that turned out not to be ovarian cancer."
http://www.medscape.com/viewarticle/750770_2
Risk Factors
"Risk Factors (of ovarian cancer)
• Increasing age, with highest occurrence in women over 50
• Family or personal history of ovarian, breast, endometrial, or colon cancer (only 10% of cases are linked to family history, however)
• Uninterrupted ovulation (having no pregnancies)
• Presence of BRCA1 or BRCA2 gene mutations"
http://womenscancerfoundation.com/gynecologic-oncology/ovarian/
Conditions
"CA 125 is the essential ovarian cancer marker. High rates are also found in cancer of the endometrium and Fallopian tubes."
https://directlabs.com/TestDetail.aspx?testid=78
"Malignant conditions associated with elevated CA 125 levels include the following:
• Epithelial ovarian carcinoma (including fallopian tube and primary serous peritoneal carcinoma): 75%-85% of cases
• Endometrial carcinoma: 25%-48% of cases
• Endocervical adenocarcinoma: 83% of cases
• Pancreatic carcinoma: 59% of cases
• Breast carcinoma: 12%-40% of cases
• Lymphoma: 35% of cases
• Lung carcinoma: 32% of cases
• Colorectal carcinoma: 20% of cases
• Squamous cervical/vaginal carcinoma: 7%-14% of cases
Benign conditions associated with elevated CA 125 levels include the following:
• Endometriosis: 88% of cases
• Cirrhosis: 40%-80% of cases
• Acute peritonitis: 75% of cases
• Acute pancreatitis: 38% of cases
• Acute pelvic inflammatory disease: 33% of cases
• First trimester of pregnancy: 2%-24% of cases
• Non-disease state: 0.6%-1.4% of healthy individuals"
http://emedicine.medscape.com/article/2087557-overview#aw2aab6b3
Other Tumor Marker Tests
"All serum tumor markers were elevated in patients with ovarian carcinoma.
Serum level of CA 15-3 was increased in patients with ovarian carcinoma (median 48.33 U/ml, normal range 0-36), while it was normal in patients with benign ovarian tumors (median 20.67 U/ml; p >0.05).
CA125 serum values were strikingly increased in ovarian carcinoma (median 264.16 IU/ml, normal range 0-35) and benign ovarian tumors (median 119.59 IU/ml; p <0.05)."
http://www.ncbi.nlm.nih.gov/pubmed/17436409
http://labtestsonline.org/understanding/analytes/tumor-markers/start/2
http://www.cancer.org/treatment/und...s/tumormarkers/tumor-markers-specific-markers
The new growth does not have the "fir-tree" appearance of the "Median canaliform dystrophy of Heller". The new growth has some ridges of the "Beau's Lines", but the newer ridges are much flatter than the ones in the top portion of my nails. This has come about, even without taking any natural folate/B12 supplements yet.