There are three main steps in the development of aggressive prostate cancer. The earliest is the appearance of microscopic clusters of cancer cells within the prostate gland: clusters that produce no symptoms and cannot be detected by normal physical examination. The second phase is for these cells to grow in bulk within the prostate gland to a size that is detectable by physical examination and is starting to cause symptoms, such as urinary problems. In the third phase, the cancer spreads outside the prostate gland into the tissues immediately surrounding it, such as lymph glands in the pelvis and abdomen, and then distantly into bones, such as spinal vertebrae.
How this progression occurs is still a matter of fairly heated argument among the experts. One group believes that all prostate cancers eventually follow this route from stage 1 to stage 3 in time. Some cancers are simply slower than others in doing so. They have evidence that it can take four years for a prostate cancer to double in size, so that it may be ten years before it reaches 1 ml in volume. This is the size at which many cancers start to cause symptoms, although many more are undetected until they are two or three times as big.
Other researchers propose that for prostate cancers to progress they need to undergo several successive genetic mutations. The first mutation may produce the well-differentiated cancers mentioned above, but they need a second to turn them into aggressive undifferentiated cancers, and perhaps a third to cause them to spread further than the prostate. The chances of men having three successive mutations in a cancer are very small, which is why aggressive, life-threatening cancers are relatively rare. This could be why so many men with microscopic cancers never go on to have serious disease.
This “multistep’ explanation for the development of cancer may also explain why, although microscopic prostate cancer rates are similar all over the world, the rates of aggressive, spreading cancers differ widely. In the countries with the higher prostate cancer death rates, environmental conditions that lead to mutations may be changing the nature of the disease.