Stages of cancer

taken from Small Gland, Big Problem 4th Edition
by Professor Roger Kirby, Health Press 2011

The earliest stage in uncontrolled cell growth is not actual malignancy, but pre-malignancy, known medically as prostatic intraepithelial neoplasia (PIN for short). PIN is characterized by a ‘heaping up’ of cells within the prostate, but there is no invasion of healthy tissue at this stage. With time, however, these dividing cells may develop the ability to invade the prostate tissue. Such early signs of invasion give the pathologist examining a sample (biopsy) of prostate tissue under a microscope the clue that actual cancer has developed from the pre-malignant PIN changes. At this stage, the level of PSA (see page 12) in the blood usually begins to rise – another clue that invasive prostate cancer is developing.

prostate cancer
As prostate cancer develops, it forms a nodule that can then grow and spread to the seminal vesicles and other local structures

As cancer develops from prostate cells, when looked at under the microscope, early less aggressive cancers bear a close resemblance to normal tissue. As the cancer becomes more aggressive and potentially dangerous, these similarities are progressively lost. This process is known as ‘de-differentiation’ and was described by the pathologist Dr Gleason. A sample of prostate tissue is given a ‘Gleason grade’ according to the shape, size and structure of the cells in the sample. The grading runs from 1 to 5; the higher the number, the more dangerous the cancer (see page 23). Because the cells will not appear uniform across the tissue sample, the two most prominent regions are usually assessed, and the two grades added together to give what is known as the ‘Gleason score’. Doctors can use this to estimate the risk of progression for their patients. The higher the score (from 2–10), the more potentially dangerous the cancer in terms of spread to bones and lymph nodes.

Once prostate cancer cells have developed the ability to invade tissue, they initially spread locally within the gland and then start to invade the capsule that surrounds the gland. Small tumours can be detected only by examining a biopsy of an apparently normal gland under the microscope; larger cancers can often be felt by the doctor as a firm nodule during an examination via the back passage (rectum), known as the digital rectal examination.

prostate cancer 2
As the cancer becomes more advanced, the cells are able to break off from what is known as the primary tumour. These cells enter the blood or lymphatic system, and are transported to distant parts of the body. Once deposited at a site, the cancer cells start to grow and multiply, and new secondary cancers called metastases are formed

At first, the cancer spreads locally to tissues around the prostate, such as the seminal vesicles. Eventually, however, it can spread to more distant sites, such as the bones. The mechanisms by which cancer cells acquire the life-threatening ability to spread (metastasize) are currently the subject of intense scrutiny. Central to the process is the ability to obtain a new blood supply to provide oxygen and nutrients to the cancer cells so that they can grow (all cells have these requirements). The development of a new blood supply has been termed ‘angiogenesis’, and angiogenesis inhibitors, which include the infamous drug thalidomide, as well as newer agents such as Avastin (bevacizumab), provide a very promising new avenue of treatment for prostate cancer; as yet, however, none of these has been approved for clinical use in men with prostate cancer.