Risk Factors

It is largely unknown as to what causes prostate cancer. It is thought, as with other cancers, to be a combination of environmental risk factors in conjunction with a genetic predisposition. Risk factors are not “causes,” but are factors that make you statistically more likely than others in the general population to have a certain condition. The following is list are some of the more well-known and accepted risk factors for the development of prostate cancer.

• Age
• Family History
• Race
• Dietary Fat

Advanced age, family history and race are the three most important factors. It is for this reason that men begin screening for prostate cancer at the age of 50, unless they are African American or have a family history, then screening can begin earlier. Prostate cancer screening should be a shared decision between you and your caregiver.

Approximately 9% of all prostate cancers are termed “familial.” This is a form of cancer that is genetically passed on in an autosomal dominant fashion. This tends to cause prostate cancer in younger individuals (less than age 55). Newer genetic tests can be performed to see if you carry any of these genetic risk factors. It is recommended to check if you have higher grades of prostate cancer or have certain relatives with prostate cancer.

Symptoms

Localized prostate cancer does not cause any symptoms. Until the development of the PSA blood test, detection of localized prostate cancer could only occur if the cancer grew to the point where it was able to be felt via a digital rectal examination (DRE) or if it was found incidentally during transurethral resection of the prostate for obstructive symptoms.

Prostate cancer that has metastasized may cause pain, especially from spread to the bones. Weakness from anemia may occur if prostate cancer has affected multiple areas of the bone marrow, limiting the body’s ability to produce red blood cells. In advanced cases, malignant enlargement of the prostate can obstruct urine flow, resulting in backup of urine into the kidneys (hydronephrosis) with possible kidney failure if this process affects both kidneys.

Locally advanced prostate cancers may obstruct urinary flow and/or cause severe irritation in the bladder region when the cancer extends from the prostate into the base of the bladder. Treatment of this locally advanced cancer can be very difficult. Obstruction to urinary flow may be opened by transurethral resection of the prostate, but there is a delicate balance between opening the urethra adequately to void and opening the urine passage too much, resulting in incontinence.

Early Detection

We consider the use of a number of tests to look for warning signs of prostate cancer. The most common of these is the PSA blood test. Other detection tests/techniques include:

• Percent-free PSA
• PSA velocity
• PSA density
• Age-specific PSA ranges
• Digital rectal exam (DRE)
• Transrectal ultrasound (TRUS)
• Prostate MRI
• Genetic Testing
• Blood tests (4K etc.)
• Urine tests (ExoDx etc.)

These early detection tests help us understand your risk for having clinically significant prostate cancer. If the results of one or more of these tests are abnormal, you may need a prostate biopsy to determine if you have cancer.

Prostate Cancer Grading and Staging

First things first. What is the difference between grade and stage? The grade of the cancer is how aggressive it is. It’s the personality or predisposition of cancer cells to want to be aggressive. The lower the grade the more favorable the prognosis. The stage of a cancer is where is it at the moment. While stage usually follows grade you can have a high grade (aggressive) tumor that is low stage (localized) and you can have low grade tumors that if left long enough can spread and be higher or later stage.

Grading

Initially prostate cancer was graded using the Gleason Sum. Each area of cancer was graded between 1 and 5 (5 being the most aggressive) and the most common area was added to the next most common area. For example, a patient could have mostly Gleason score 3 but some 4 and they would be a Gl 3+4=7. After some time, it was decided that Gl 1 & 2 were not actually cancer. This gives us 2 problems. We have a grading system that ranges from 6-10 (confusing) and we have Gl 7 that can be less aggressive (3+4) or more aggressive (4+3). These limitations were addressed recently when we switched and now use grading groups (1-5).

Old Gleason Sum	New Grade Group	What it means
3+3=6	1	Cells look like normal prostate cells, slow growing, low likelihood to spread.
3+4=7	2	More aggressive looking than Group 1 but still similar to normal prostate. Low probability of spread but more risk than group 1.
4+3=7	3	Cells look more aggressive than normal prostate cells. These cancers usually grow at an intermediate rate and are more likely to spread than group 2.
4+4=8	4	These are aggressive looking cells and grow fast and like to spread.
4/5+4/5=9/10	5	These cells look almost nothing like normal prostate cells. They grow fast and are quick to want to spread.

Stage indicates where the cancer is at and how far it has progressed. This is different than the grade, which is how aggressive a cancer is going to behave. Since the widespread use of PSA testing, most patients diagnosed with prostate cancer have non-metastatic or low stage disease at presentation. Most patients are only familiar with the Tumor (T-stage) staging but true staging includes N or Nodal stage and M or metastasis (spread) stage.

Stage I – (T1) – Tumor remains confined to the prostate and is too small to be detected on DRE. This is an incidentally found cancer either by an elevated PSA or found after a transurethral resection of the prostate.
Stage II – (T2) – Tumor is still confined to the prostate; 2a < ½ of 1 lobe, 2b >1/2 of 1 lobe, 2c tumor in both lobes.
Stage III – (T3) – The prostate cancer has spread through the prostatic capsule and may involve locally surrounding tissues; 3a extracapsular extension, 3b tumor invades seminal vesicles.
Stage IV – (T4) – Locally advanced (T4) or metastatic (Stage IV) prostate cancer in which the cancer involves local structures like the bladder or rectum. Stage IV also includes patients with nodal involvement (N1), bone involvement (M1b), or metastasis to other sites like lung or liver
(M1c).

Prostate Cancer Risk Groups

To help patients understand their risk many doctors use a combination of grade, T stage, initial PSA and biopsy results to separate patients into the following risk groups. These help direct patients

INITIAL RISK STRATIFICATION AND STAGING WORKUP FOR CLINICALLY LOCALIZED DISEASE*

Risk Group	Clinical/Pathologic Features	Additional Evaluation
Very low	Has all of the following: • T1C • Grade Group 1 • PSA <10 ng/mL • Fewer than 3 prostate biopsy fragments/cores positive, ≤50% cancer in each fragment/core • PSA density <0.15 ng/mL/g	Consider confirmatory prostate biopsy ± mpMRI if not performed prior to biopsy to establish candidacy for active surveillance
Low	Has all of the following but does not qualify for very low risk: • cT1-cT2a • Grade Group 1 • PSA <10 ng/mL	Consider confirmatory prostate biopsy ± mpMRI if not performed prior to biopsy to establish candidacy for active surveillance
Intermediate	Has all of the following: • No high-risk group features • No very-high-risk group features • Has one or more intermediate risk factors (IRFs): -cT2b-cT2c -Grade Group 2 or 3 -PSA 10-20 ng/mL	Favorable intermediate	Has all of the following: • 1 IRF • Grade Group 1 or 2 • <50% biopsy cores positive (eg <6 of 12 cores)	Consider confirmatory prostate biopsy ± mpMRI if not performed prior to biopsy for those considering active surveillance
		Unfavorable   intermediate	Has one or more of the following: • 2 or 3 IRFS • Grade Group 3 • > 50% biopsy cores positive (eg, > 6 of 12 cores)	Bone and soft tissue imaging
High	Has no very-high-risk features and has exactly one high-risk feature: • cT3a OR • Grade Group 4 or Grade Group 5 OR • PSA >20 ng/mL	Bone and soft tissue imaging
Very High	Has at least one of the following: • CT3b-CT4 • Primary Gleason pattern 5 • 2 or 3 high-risk features • >4 cores with Grade Group 4 or 5	Bone and soft tissue imaging

*From NCCN Guidelines Ver 1.2022 – Sept 10, 2021

The risk groups can help determine what other tests should be done as well as direct treatment.

Treatment Options

The following is a list of possible treatment options. The PeeDocs will work with you to recommend a course of treatment that offers the greatest chance of success for you. These are only brief descriptions of each.

Active Surveillance

Patients with very low risk prostate cancer and some with low risk prostate cancer are good candidates for active surveillance. These patients are followed closely to make sure there is no progression. Those patients who are followed expectantly should have regular physical examinations, serial PSA levels, MRIs and occasional biopsies. Progression of the disease would be an indication to change plans and treatment modality.

Cryosurgery

This involves placing several percutaneous probes into the prostate and the prostate is then frozen, thawed and then frozen again. The freezing and thawing kill prostate cancer cells. This is done under anesthesia.