A recent review by the Cochrane collaboration looked at 7 large mammography trials -- involving half a million women -- and the results raise some questions about large breast screening programs. The review found that mammography screening in women 50-70 years of age likely reduces breast cancer mortality, but the magnitude of the effect is uncertain and screening will also result in some women getting a cancer diagnosis even though their tumour wouldn't have led to death or sickness. It's currently not possible to tell which women these are, and they're therefore likely to have breasts and lumps removed and to receive radiotherapy unnecessarily. Considering all trials, the reduction in breast cancer mortality comes out to be 20%, but as the effect is lower in the highest quality trials, a more reasonable estimate is a 15% relative risk reduction. Given the breast cancer risk of women in these trials, this translates into an absolute risk reduction of 0.05%, meaning that for every 2,000 women getting screened throughout 10 years, 1 will have her life prolonged. In addition, 10 healthy women, who wouldn't have been diagnosed if there hadn't been screening, will be unnecessarily treated as breast cancer patients.5 It's thus not clear whether screening does more good than harm.5

Preventing cervical cancer
Even though there's no randomized trial for the efficacy of the Pap smear (nor will there ever be), everyone agrees that cervical cancer is one malignancy for which death and serious effects could be completely prevented if all women who've ever been sexually active had the test at reasonable intervals. The expected impact of immunizing young women against cervical cancer is even more promising.

There's been a continuing debate as to the best frequency for the Pap test. Current evidence suggests that after becoming sexually active, all women should have an annual Pap smear for 2 years, followed by 1 test every 3 years up to age 70. If a woman appears to have an above-average risk of cervical cancer, the test may be done more frequently. Unfortunately, the most common pattern in Canada is that the majority of women at low risk receive annual Pap smears, while 30-40% of women don't undergo the procedure at all. The lowest death rate from cervical cancer in the world is found in Finland, where Pap tests are done every 5-7 years on almost the entire female population. In Canada, the mortality rate for cervical cancer has been steady over the past decade,6 indicating that we need to screen a higher percentage of women to see improvements.

In several provinces, girls aged 10-12 have been offered the HPV vaccine effective against 4 strains of the virus that cause both cervical cancer and genital warts. The vaccine can be used in women up to age 26 who haven't suffered an HPV infection. To prevent 1 case of condyloma, you need to immunize 8 women; to prevent 1 episode of cervical cancer, you have to give the HPV shot to 324 individuals. The vaccine is considered safe and efficacious,7-9 but even the young women who've received it will need to continue a Pap smear program because of the uncertain long-term effects of the vaccine.

Some screening experts are suggesting that Pap smears shouldn't start until women are 30. The reason is that cervical cancer occurs in middle age, and more than half of all dysplasia found on Pap smears in young women disappears and doesn't progress to cancer. When dysplasia is found, physicians often do a cone biopsy, which in turn predisposes women to miscarriages.

Screening for prostate cancer
The digital rectal examination isn't recommended as a screening test as it'll miss > 50% of cancers. The prostate specific antigen (PSA) screening test detects most prostate cancer with some accuracy, but about 80% of men with this cancer will die from causes other than the malignancy -- indeed, only 15-20% of men with prostate cancer die from the disease. Treatment has modestly lowered the mortality rate, but the benefit is small compared to the rise in screening rates and dramatic increase in prostate cancer diagnoses (Figure 1).10

Frankel et al estimate that if 1 million men over 50 were screened for PSA and the cut-off were set at 4 ng/mL, 110,000 men would have elevated PSA on the first test.11 Of these, 90,000 would get a biopsy and 20,000 would be found to have cancer. Of the 10,000 undergoing a prosta¡tectomy, 3,000 would be left with chronic incontinence, 4,000 would find themselves impotent, and > 100 would die from the surgery. We continue to await evidence of benefit to counteract all this morbidity and mortality.

Two large randomized trials of PSA and digital rectal exam screening commenced in 1993.12-14 The European Randomised Study of Prostate Cancer (ERSPC) trial has enrolled > 200,000 men from several countries, with follow-up times up to 13 years. The Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial in North America has enrolled about 76,700 men. There have been preliminary reports from both studies, but they don't plan to report mortality results for 2 or 3 more years. Both trials are being rigorously monitored and neither one has been discontinued due to a significant benefit found in the screened group. So it appears that for all the morbidity and mortality associated with PSA screening, there's no substantial early benefit. This is a screening test that has the potential to cause more harm than good. While it's difficult to explain this to patients, it's important for them to understand this dilemma before they undergo what seems like a simple blood test.

Colorectal cancer screening
Over the past year, 4 provinces have launched colorectal cancer screening programs for all adults over 50. Indeed, this cancer has good potential for lowering mortality with screening programs. It's recommended to screen those at average risk with fecal occult blood testing (FOBT) at least once every 2 years; those above average risk require regular colonoscopy.

To determine an individual's risk (see also Table 2) and the appropriate screening interval, it's useful to refer to the following categories:15

• Category 1 (at or slightly above average risk)
  No personal history of bowel cancer, advanced adenoma, or chronic ulcerative colitis, AND either no close relatives with bowel cancer or one 1st-degree or 2nd-degree relative with bowel cancer diagnosed at age 55 years or older. These people are screened with FOBT every 2 years, starting at age 50.
• Category 2 (moderately increased risk)
  One 1st-degree relative with bowel cancer diagnosed before age 55 (without the potentially high-risk features listed below), OR two 1st-degree or one 1st- and one 2nd-degree relative(s) on the same side of the family with bowel cancer diagnosed at any age (without the potentially high-risk features listed below). These people are screened with colon¡oscopy once every 5 years, starting at age 50.
• Category 3 (at potentially high risk)
  Three or more 1st-degree or a combination of 1st- and 2nd-degree relatives on the same side of the family diagnosed with bowel cancer (hereditary nonpolyposis colorectal cancer [HNPCC]), OR two or more 1st- or 2nd-degree relatives on the same side of the family diagnosed with bowel cancer, including any of the following high-risk features: multiple bowel cancers in one person, bowel cancer before the age of 50 years, at least one relative with cancer of the endometrium, ovary, stomach, small bowel, renal pelvis, ureter, biliary tract or brain, OR at least one 1st-degree relative with a large number of adenomas throughout the large bowel (suspected familial adenomatous polyposis [FAP]), OR somebody in the family with a high-risk mutation in the adenomatous polyposis coli (APC) gene or one of the mismatch repair (MMR) genes. These people require colonoscopy as frequently as once every 3 years.

Although FOBT doesn't have very good test characteristics, there's convincing evidence that thousands of Canadian lives could be saved annually, even if only 50% of those eligible were screened.