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Relationship between aggressiveness and prostate cancer

Prostate cancer is very frequent in men in Spain (27,800 cases diagnosed in 2012 according to the Spanish Society of Medical Oncology, SEOM). Although there is a simple treatment for the majority of cases, it is the third cause of death among men, resulting in 5,481 deaths in 2012 only following colorectal and lung cancers. The reason for this elevated number is that there is a type that is 15% more aggressive (known as metastatic castration-resistant prostate cancer).

It is now known that there is a gene, GATA2, that is especially active in these types of tumors and that it is resistant to chemotherapy in the treatment of prostate cancer. GATA2 is a gene related to the differentiation and development of eukaryotic organisms (those which have complex cells like those of humans) and which has been linked to some lung and blood cancers. A route has been discovered, a procession of processes that begins in GATA2 (called master gene) and which extends to the phases that influence cellular proliferation.

Each step in these chain reactions involve new genes (or their proteins, which in reality are those that act). IGF2, another of the involved proteins (a growth factor) is also important in this succession of processes, the reason being that, among other causes, there are already drugs that inhibit it and are well-tolerated by persons.

To determine the most adequate treatment for prostate cancer, it is important to classify the tumor and to determine its phase of development.

The classification system most widely used is the TNM system where:

  • T describes the size of the original (primary) tumor and whether it has invaded nearby tissue,
  • N describes nearby (regional) lymph nodes that are involved,
  • M describes distant metastasis (spread of cancer from one part of the body to another).

Based on these aspects, prostate cancer is classified in the following stages :

  • Stage I: the cancer tumor is not palpable nor visible by diagnostic means. Its diagnosis is accidental (i.e., when a patient goes to the urologist for other reasons)).
  • Stage II: the tumor is visible or palpable but is confined to the prostate gland and seems not to have spread.
  • Stage III: the cancer extends outside the prostate and has/may have spread to tissues next to your prostate such as the seminal vesicles.
  • Stage IV: The cancer has spread to other parts of the body, such as the bladder, rectum, bone, liver, lungs, or lymph nodes.

The Gleason System is used to classify the aggressiveness of the tumor cells into categories. The system is named after the North American pathologist who proposed this grading system.

The Gleason Scoring System

This system evaluates the aspect and distribution of the tumor cells based on how they look under a microscope. Gleason scores are categorized in five different ranges or grades from lower to higher aggressiveness. These ranges go from one (low) to five (high) and indicate how likely it is the tumor will spread.

Since cells within a same prostate cancer do not always fall into the same range, two predominate patterns are identified, scored and added up to obtain a total Gleason score. This can be between 2 (1+1), the minimum and 10 (5+5), the most aggressive. Up to grade 6, the tumors are considered to be less aggressive, from 8-10 most aggressive and 7 intermediate.

PRONOSTIC FACTORS

Certain characteristics of the illness related to the increased probability that over time the illness will progress are called prognostic factors or progress risks. For prostate cancer, the individual risk factors are the clinical stage, the Gleason score of the prostate biopsy and the PSA pre-treatment levels.

The combination of said factors forming risk groups permits doctors to obtain more exact prognostic information than with each one individually. The prognostic estimate by means of forming groups of risk factors has gained popularity for its simplicity and ease of use; nonetheless the homogeneity of a risk within a same group is not guaranteed given that a same weight is given to each variable (stage, Gleason and PSA). To quantify the risk in a specific tumor, nonograms or predictive tables which take into account the interactive effects of each and all the of independent prognostic factors have to be constructed.

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