Most cases of prostate cancer grow very slowly, and many prostate cancers never extend beyond the prostatic capsule. Many men die with, rather than from, prostate cancer. This is why active surveillance, in which the prostate is monitored for progress of the disease, is often a viable alternative to treatment.

Prostate tumors often arise in the peripheral zone of the gland, sometimes in the transition zone, and rarely in the central zone. (Cancer pathology is usually described in terms of zones of the prostate gland, rather than lobes.) In the first stages of prostate cancer, the tumor remains confined within the prostatic capsule. Later in the course of the disease, as the tumor becomes larger, the cancer may penetrate through the capsule. Symptoms of prostate cancer may be felt only in these later stages.

When the cancer cells have penetrated through the prostatic capsule they may spread locally to nearby organs, lymph nodes, and tissues. Transition-zone tumors often spread to the bladder neck, while peripheral-zone tumors may invade the ejaculatory ducts, seminal vesicles, or rectum.

An important factor in the progression of the disease is the tumor grade. Low-grade tumors with cells that are well differentiated (look more like normal prostate cells) often have a slower course, while high-grade tumors, which have poorly differentiated cells, may metastasize rapidly. However, this doesn't always hold true: sometimes low-grade tumors may be very aggressive. In addition, prostate cancer cells may become more aggressive as the size of the tumor increases.

Cancer Metastasis

Metastasis occurs when cancer cells spread to sites distant from the site where they first arose or its neighboring tissues. Metastasis is more likely to occur during advanced prostate cancer than in its earlier stages, particularly when the cancerous cells have invaded nearby lymph nodes. From those nodes they can enter into the lymphatic system and spread to areas distant from the original site through the lymph vessels. Cancerous cells can also penetrate into capillaries and migrate via the bloodstream. The cells can become lodged in smaller blood vessels and start to form new tumors there, distant from the prostate. Prostate cancer often metastasizes into the bones, but the reasons why this happens so frequently are unclear.

The Lymphatic System

The lymphatic system works in concert with the immune system and has several functions in the body. The lymphatic system:

• Combats invasive foreign bodies like bacteria, viruses, and fungi
• Drains interstitial fluid back into the bloodstream from the tissues
• Filters lymph
• Filters the blood

The lymphatic system includes the lymphatic vessels, lymph, lymph nodes, spleen, thymus, bone marrow, and a few other organs.

• Lymphatic vessels form a sort of parallel circulatory system, branching throughout the tissues of the body.
• Lymph is a colorless liquid found within the lymphatic vessels. It's collected from tissues in all parts of the body as interstitial fluid, and then travels to at least one lymph node for filtering before returning to the bloodstream via the veins. Lymph carries large numbers of lymphocytes (white blood cells).
• Lymph nodes are found in the armpits, on either side of the groin, on either side of the neck, and in the abdomen, pelvis, and chest. Lymph nodes filter the lymph fluid as it passes through them, and macrophages inside the lymph nodes kill intruders, such as bacteria.
• The spleen produces lymphocytes and filters the blood.
• The thymus helps to produce white blood cells. o Bone marrow produces white (and red) blood cells.

When cancer cells break off from a tumor, they often become trapped in the nearest lymph node. That's why doctors check the lymph nodes first when they are determining how far a cancer has grown or spread.

Staging Using the TNM System

If the Gleason score, the DRE, and the PSA test show the cancer is likely to have spread, imaging and other tests are done to determine the extent and location of the cancer. Based on this information, the cancer is assigned a stage.

There are a number of systems for staging prostate cancer, but the one most often used in the US is the American Joint Committee on Cancer (AJCC) TNM staging system. TNM categories describe the extent of the primary tumor (T), whether the cancer has spread to nearby lymph nodes (N), and the presence or absence of metastasis (M).

• T categories (most of the T categories have subcategories as well)
  
  • T1: The tumor can't be felt in a DRE or seen with imaging devices.
  • T2: The cancer can be felt during a digital rectal exam (DRE), but it appears to be confined to the prostate gland.
  • T3: The cancer has begun to grow and spread outside the prostate. It may have spread to the seminal vesicles.
  • T4: The cancer has grown into tissues adjacent to the prostate (other than the seminal vesicles), such as the bladder muscle, the rectum, and/or the wall of the pelvis.
• N categories
  
  
  • N0: The cancer has not spread to any lymph nodes.
  • N1: The cancer has spread to one or more nearby nodes.
• M categories
  
  
  • M0: The cancer has not spread beyond the nearby lymph nodes.
  • M1: The cancer has spread beyond the nearby nodes.
    
    • M1a: The cancer has spread to nodes outside of the pelvis.
    • M1b: The cancer has spread to the bones.
    • M1c: The cancer has spread to other organs (such as lungs, liver, brain)

Stage Groupings

When the TNM categories have been determined, this information is combined with the Gleason score to form a simplified, overall score of Stage I-IV prostate cancer. This process is called stage grouping. The stages are summarized in the chart below.

Cancer Stages

Stage	Features
I	The cancer is still within the prostate. It was found during a transurethral resection. There is no spread to lymph nodes or to distant organs, a low Gleason score (2-4), and less than 5% of the biopsy tissue contained cancer.
II	The cancer is still within the prostate. It has not spread to the lymph nodes or elsewhere in the body and one of the following applies: It was found during a transurethral resection and it has a Gleason score of 5 or higher, and less than 5% of the tissue contained cancer. It was found during a transurethral resection and more than 5% of the tissue contained cancer.. It was found because of a high PSA level. It cannot be felt on DRE or seen on transrectal ultrasound, and was diagnosed by needle biopsy. It can be felt by DRE or seen on transrectal ultrasound.
III	The tumor has spread outside the prostate and may have spread to the seminal vesicles, but it has not spread to the lymph nodes or elsewhere in the body.
IV	One or more of the following apply: The cancer has spread to tissues next to the prostate (other than seminal vesicles), such as the muscles that help control urination, the rectum, or the wall of the pelvis. The cancer has spread to the lymph nodes. The cancer has spread to other, more distant places in the body

[Source: American Cancer Society]

Biopsy

Another way of finding out if cancer has spread outside of the prostatic capsule is to biopsy the lymph nodes. One or more or more of the lymph nodes near the prostate are removed (called a lymph node dissection or lymphadenectomy) and checked by a pathologist. Lymph node biopsies are generally done only if there is a good chance the cancer has spread, for instance if there is a high PSA level or a Gleason score over 7.

There are several different ways to biopsy the lymph nodes:

• Surgical biopsy. This is often done during a radical prostatectomy (removal of the entire prostate), before removing the gland. Lymph nodes are removed through an incision in the abdomen and examined by a pathologist while the patient is still under anesthesia. If the nodes contain cancer, the operation may be stopped and the prostate left in place. Removing the prostate would be unlikely to cure the cancer, and radical prostatectomies can have serious complications.
• Laparoscopic biopsy. An operation sometimes performed to find out if cancer has spread to the lymph nodes but a radical prostatectomy isn't planned (for example, if the patient has chosen radiation treatment instead). The lymph nodes are removed through small openings in the abdomen using long instruments. The surgeon can see into the abdomen through a video camera attached to a long, slender tube.
• Fine needle aspiration (FNA). This is done if a lymph node appears enlarged on an imaging test (CT or MRI). A long, thin needle with a syringe is inserted through the abdomen and into the enlarged node. The syringe allows for the removal of a small amount of tissue from the node.