Friday, March 12, 2010

Screening for cancer.

The American Cancer Society is urging a more cautious approach to screening for prostate cancer. Among its recommendations is the advice that men with a life expectancy of less than 10 years should not be offered screening. The chairman of the committee said that two decades into the the PSA era of prostate cancer screening, the overall value of early detection in reducing the morbidity and mortality from prostate cancer remains unclear. One interesting statistic was that for each man who experienced the presumed benefit of screening, more than 20 had to be diagnosed with prostate cancer. This represents the most optimistic view assuming that the entire decline in prostate cancer mortality is due to screening. In fact the benefit ratio could be as poor as 1 in 50.

Raised PSA levels are frequently caused by benign prostatic hypertrophy or by a low grade malignancy that is unlikely to cause problems during the lifetime of the indidividuals. These people still have to undergo prostatic biopsy (which can be painful) and if it indicative of a low grade cancer they have the worry of deciding whether or not they should be treated. If they decide not to be treated then the horrors of watchful waiting beset them.

If it is deemed necessary to try and treat the prostate cancer surgically, the patient does not have a smooth passage. Apart from the immediate complications of bleeding and urinary stricture, the two primary longer term adverse effects of surgery are urinary and sexual. Data would suggest that long-term incontinence rates after surgery are from 12% to 16%. Long-term rates of erectile dysfunction after surgery in contemporary series ranged from 19% to 27%. It has been recently reported that, as with urinary incontinence, there is a higher rate of erectile dysfunction with minimally invasive radical prostatectomy compared with radical retropubic prostatectomy.

Radiation therapy is also not without toxicity. Acute toxicities that can present during treatment in up to 50% of men include urgency, dysuria, and nocturia, loose bowel movements or diarrhea, and hemorrhoidal and anal irritation. As with surgery, the most commonly encountered late toxicity is erectile dysfunction, which affects up to 50% of men.

Prostate cancer is very sensitive to the removal of a testosterone drive. Among the most common types of side effects of hormonal therapy are increased risk for weight gain, obesity, and diabetes; cardiovascular disease; breast enlargement and tenderness; sexual problems, including diminished sex drive and erectile dysfunction; emotional changes, including anger, sadness, and, in many, a generalized sense of fatigue; osteoporosis; loss of muscle strength and mass, which also increases the risk of falls in older men, predisposing them to bony fractures; anemia, which also contributes to fatigue; and cognitive changes, such as impaired thought processes and memory loss.

Similar fears have been raised about breast cancer screening. The authors of this report come from the Nordic Cochrane Center (the word 'Cochrane' usually implies a sensible approach to the statistics of health care). The report is in response to a report from the UK NHS Breast Cancer Screening Program which celebrates the 20th anniversary of cancer screening in the UK with the statement that the program saves 1400 lives a year

The authors regard this as propaganda, and since it is in line with the British government's expectation I would say that it just plain lying. No other breast screening program makes such claims. For example the Swedish mammography service claims to save 1 woman in 1000 screened, not the 2.8 per 1000 claimed here. It is easy to prove that the claim is nonsense. The decline in breast cancer mortality since 1989 in women who were screened (ie aged between 50 and 64) was 35%. But for women aged 40-49 (who weren't screened) the decline was 41% and for those aged 65-69 (who weren't screened until 2001) the decline was 38%. It would be special pleading to suggest that some other factor was responsible for the better outcome in those women who weren't screened, while the slightly smaller improvement in those who were screened was because they were screened. Moreover the improvement in survival began a couple of years before screening began. It is more likely that treatment has improved, most likely because of tamoxifen.

The most serious hazard of mammography is the overdiagnosis and overtreatment of healthy women who would not have acquired breast cancer in their lifetime had they not attended screening. It has been estimated that as many as a third of breast cancers picked up by screening are unnecessary diagnoses. That amounts to about 7000 breast cancer diagnoses a year in the UK.

In 2007 there were 83,728 recalls after initial screening in the UK. Of these, 14,753 were eventually found to have cancer - in other words 70,000 women were worried unnecessarily. About 40% of those recalled (about 34,000) undergo needle biopsy. There are about 2500 excision biopsies every year of which nearly 1700 will show a benign lesion. It has been estimated that screening leads to an extra 20% mastectomies each year, but some of these will be for carcinoma-in-situ (this is the breast cancer version of monoclonal B-cell lymphocytosis). 29% of carcinoma-in-situ cases were treated by mastectomy. Now perhaps 40% of cases of carcinoma-in-situ cases will progress to full blown carcinoma, but which 40%? There is no knowing whether they will include any of the 29% operated on.

Many of my readers will know what it is like to walk around with a cancer diagnosis, even if the doctors tell you that no treatment is necessary. The problem with screening is that it assumes that 'cancers' picked up by screening will behave in the same way as cancers picked up when they present in the normal way. There is quite a lot of evidence that they do not. Nor should it be assumed that a cancer patient who survives 12 years after diagnosis following screening has done any better than the patient who dies 8 years after diagnosis is a conventional way. Both might have died exactly the same length of time after the first cancer cell appeared; it's just that the first patient has known about it longer.

Last year the diagnostic criteria for CLL changed. No longer do 5000 lymphocytes define the disease; you have to have 5000 B-lymphocytes. B-lymphocytes normally comprise 10-18% of all lymphocytes, so you see that the threshold has been raised considerably. Patients who last year thought they had leukemia have now been told that they have a benign condition. Unlike other forms of leukemia, CLL is very similar to other cancers that occur predominately in older people. It may well be true that there are other cancers for which a relatively benign form exists. If we have very sensitive forms of diagnosis we may well end up diagnosing all sorts of cancer that never needed diagnosis.

It is now a year since I was diagnosed with cancer. In retrospect six months previously a small enlarged lymph node was detected on CT scan. It was known from colonoscopy to be situated somewhere near the junction of small and large bowel. At operation no primary tumor was found, but the lymph node was found to contain well-differentiated adenocarcinoma. I was given 9 course of chemotherapy on an intense schedule. At the end of this a residual and inoperable was 75% smaller than before the chemotherapy. Three months on the node was unchanged on CT scan and I am due another scan shortly. My CEA test gave an answer of 3 at the time of the operation, which does not indicate a large amount of cancer, but now it is <1. I have nothing to suggest that my disease has recurred.

Even though my cancer had spread at diagnosis, this clearly does not mean that it was an advanced disease. With breast cancer we know it to be a systemic disease even at an early stage of diagnosis. Bowel cancer may well be the same. Now I begin to ask myself the question as to whether my screening test was wise. I certainly had no symptoms prior to diagnosis and I have suffered quite a lot in the ensuing year. Perhaps I should have had the disease for many years before it drew attention to itself; perhaps it never would have done and I would have had my coronary in bed at the age of 90. On the other hand, perhaps it has behaved so well because I had a hefty dose of chemo while it was still small. I guess I will never know.


Anonymous said...

You're right. We never know.

As far as the CLL and WBC go, at diagnosis I had a WBC of around 10k. It was presumed I had an infection as I had an abscessed wisdom tooth, which was extracted (painful).

I did have CLL, though, and at 48. I believe I did have CLL for years before, though, because I noticed small hand cuts were not healing normally. I had to soak with very hot water to quell the infection. I was puzzled at the time but didn't put two and two together. My WBC presumably was less that 10k so it probably wouldn't have been picked up anyway.

Screening occurs for CLL all of the time; anytime one has a CBC. But I doubt early screening has helped CLL patients much, but some with aggressive CLL might have been.

Good news on your cancer. Stay healthy. You are a valued resource!

Anonymous said...

As you know Dr. Hamblin, I agree so very much with this; needlessly early diagnosis can seriously damage lives, both physically, mentally and have serious financial consequenses for the unfortunate person cought. And as you quite correctly state, watch and wait is torture. I do hope "they" take note of what you say; being someone respected in the profession.

Birdie said...

Yes sometimes I think the diagnosis is worse then the cancer when given way to soon or if at all needed.

Thanks for your blog it has been very helpful in sorting through all the emotional and statistical data around me.