A primer on prostate cancer
On autopsy of men with no known prostate cancer, microscopic prostate cancer is found in 20 per cent of men aged 50-59, almost 30 percent of men 60-69, 36 per cent of men 70-79 (51 per cent of Blacks 70-79) and 47 per cent of men above 80.
Prostate cancer is the most common cancer among Canadian men (excluding non-melanoma skin cancers).
About one in eight men one in six Black men including O.J. Simpson) will be diagnosed with prostate cancer in their lifetime and one in 29 will die from it.
But many, many men will die with prostate cancer without ever even knowing they had it.
In Canada, over 25,000 men will be diagnosed in 2024 with prostate cancer, 20 per cent of all new cancer cases in men. 4,600 men will die from prostate cancer, 10 per cent of all cancer deaths in men.
It is the third leading cause of death from cancer in men in Canada, after lung cancer and colorectal cancer.
The number of deaths from prostate cancer reached 45.1 per 100,000 men in 1995 and has fallen to 22.7 per 100,000.
The increase in prostate cancer incidence largely mirrors screening using the Prostate-Specific Antigen (PSA) test.
The death rate for prostate cancer has decreased reflecting improved treatment.
Prostate cancer is one of the least preventable cancers, which underscores the importance of advancements in detection and treatment, but is almost 100 per cent survivable if detected before it spreads.
Prostate cancer is rare in men younger than 40, but the chance of having prostate cancer rises rapidly after age 50.
About 99 per cent of cases occur after age 50, 60 percent in men older than 65
A first-degree relative with the disease increases the risk two to three times.
The average age of diagnosis is 66; 10 per cent of men newly diagnosed with prostate cancer are under 55.
Worldwide, cancers historically restricted to older age groups are now being diagnosed in younger adults, including colorectal, breast, oesophageal, gastric and pancreatic cancers.
There's been an increase in early-onset prostate cancer in men between 15 and 40 years old.
Prostate cancer diagnosed in younger men tends to be more aggressive and more advanced with a lower rate of survival than older men.
The average five-year survival rate for prostate cancer is between 95 per cent and 100 percent for men ages 40-80.
For men ages 25-34, the 5-year survival rate is 80 per cent. For men ages 20-29, it's 50 per cent. For men ages 15-25, it's 30 per cent.
Development of male-pattern baldness, age-related prostate enlargement (benign prostatic hypertrophy) and prostate cancer are all dependent upon the presence of the testes, and orchidectomy before the age of 20 prevents them.
As well, removal of the testes early in life extends male lifespan - castration at age 11 increases longevity by 11 years, at age 21 by four years.
However, I think most men would still prefer to hang on to their balls.
Prostate-Specific Antigen (PSA) screening detects many cancers that would have otherwise gone undiagnosed. Ontario New Democrats proposed that the Ontario government pick up the cost of a PSA screening test ($35) but this was turned down by the Conservative government.
The PSA test is currently covered by eight other provinces.
Although only about one in
456 men under age 50 will be diagnosed, the rate shoots up to 1 in 54 for ages 50 to 59, 1 in 19 for ages 60 to 69, and 1 in 10 for men 70 and older.
Worldwide, Black men have the greatest risk of having this disease, followed by Caucasians, with the lowest incidences among Asian men.
To estimate the prevalence of undiagnosed, asymptomatic prostate cancer, studies of prostate cancer discovered incidentally at autopsy for unrelated causes of death were done among 6,024 men.
Prostate cancer was found in 20 per cent of men aged 50-59, almost 30 per cent of men 60-69, 36 per cent of men 70-79 (51 per cent of Blacks 70-79) and 47 per cent of men above 80.
This enormous prevalence, coupled with the high sensitivity of PSA screening, has led to the marked increase in the apparent incidence of prostate cancer.
Projected to the current age distribution, these data suggest roughly four million Canadian men have potentially detectable but undiagnosed prostate cancer - the vast majority of whom will die with it, not from it.
Most prostate cancers grow slowly and are confined to the prostate gland, where they may not cause any serious harm and need minimal or even no treatment.
However, some types are aggressive and can spread quickly.
Prostate cancer that's detected early — when it's still confined to the prostate gland — has the best chance for successful treatment.
The five-year net survival for prostate cancer of all stages is 93 per cent.
When detected early, the fiveyear survival rate is close to 100 per cent.
Detected late, it drops to 28 per cent.
PROSTATE CANCER SCREENING
Digital rectal exam
If your doctor finds any abnormalities during digital rectal exam you will need further tests. Most new doctors don't do this anymore, relying on the PSA.
Prostate-Specific Antigen (PSA) test
Prostate-Specific Antigen (PSA) is produced by both normal prostate cells and prostate cancer.
So, it's normal for a small amount of PSA to be in your bloodstream.
However, if a higher-than-usual level is found, it may indicate prostate infection, inflammation, enlargement (Benign Prostatic Hypertrophy) or cancer. 17.8 per cent of men screened using PSA testing will have an unnecessary biopsy due to false positives.
Prostate Cancer Canada encourages men in their 40s to get their first PSA test.
PSA testing is not recommended for most patients over age 70 or who have a life expectancy of less than 10 years.
If they are Black or have a family history or a genetic predisposition such as BRCA1 or BRCA2, they should consider having a PSA test starting at age 40.
PSA LEVELS
■ 0 to 4 ng/mL is safe.
■ 4.0 to 10.0 ng/mL is suspicious and is associated with a 25 percent chance of having prostate cancer.
■ For men under 50, PSA levels over 2.5 ng/mL may be cause for concern.
■ For men over 60, however, PSA levels up to 4.0 ng/mL are considered normal. The amount of naturally occurring PSA in your blood gets higher as you age.
■ 10.0 ng/mL is associated with a 50 percent chance of having prostate cancer.
False positives test results are common with PSA screening only about 25 percent of men who have a prostate biopsy after an elevated PSA are found to actually have prostate cancer.
IF YOUR PSA IS HIGH
Usually the first thing doctors will do to follow up on a high PSA level is another PSA test. If the PSA level is still high, your doctor may proceed to one of these follow-up procedures:
■ PCA3 Test
■ SelectMDx test
■ Transrectal Ultrasound (TRUS)
■ MRI
■ bladder exam (Cystoscopy)
■ Prostate biopsy
Obviously, cancers are diagnosed that would never have produced any clinical symptoms meaning that hyperzealous PSA screening may over-diagnose prostate cancer with startling frequency, leading to needless interventions and surgeries.
It is estimated that between 75 and 100 men undergo unnecessary treatment, surgery and/or radiation, for every life saved.
It is not just early detection we want - we need early prediction - prediction about who will go on to develop clinical disease, metastatic spread and death.
Early detection by PSA helps tell us what and where and when, but not with whether.
PCA3 TEST
The PCA3 Test is a urine-based molecular test that detects the presence of Prostate Cancer Antigen 3 (PCA3).
PCA3 is a gene that is over-expressed specifically in prostate cancer cells rather than all prostate cells, and, if present in urine, is an indication of prostate cancer.
Benign enlargement of the prostate will not cause elevated PCA3 unlike PSA.
The PCA3 test is performed on a urine sample.
Just prior to collecting the sample, the doctor will perform a digital rectal exam (DRE) to release cells from the prostate.
The PCA3 test has a sensitivity of 95 percent and a specificity of 95 per cent - meaning only five per cent rates of false-negative or false-positive results.
University Urology Associates in Toronto is one of only a few locations in Canada where the PCA3 test is available. The PCA3 test costs $385. You'll have a fee for at least one office visit or consultation, as well.
WHEN SHOULD YOU BE TESTED FOR PCA3?
■ When you have an abnormal PSA level, with or without a negative biopsy result
■ If you have already had a negative biopsy result
■ If you have a high cancer risk, even if you have a low PSA level
■ To watch for any progression of a low-grade cancer if you are doing active surveillance
■ To monitor your cancer, if you have already had treatment for prostate cancer
Do you need a prostate biopsy? What I would do is get a PSA. If the PSA is elevated, then get a PCA3. If the PCA3 is normal a biopsy most likely is not necessary, avoiding a very painful procedure.
If the PCA3 is elevated, either get a prostate biopsy or follow up with serial PCA3 tests.
Would I go to Toronto, pay $385 for a PCA3 test and another $200 for the consultation just to avoid a prostate biopsy?
In a heartbeat.
PROSTATE CANCER MONITORING
If your PSA levels continue to be elevated yet a previous biopsy showed no cancer, you may choose to monitor your prostate health using the PCA3 tests and avoid further biopsies (they're very unpleasant) unless there's a meaningful change in your test results.
If you were found to have prostate cancer, PCA3 levels can help evaluate the aggressiveness of the tumour - the higher the PCA3, the more aggressive the cancer.
SELECTMDX
SelectMDx is a urine test that measures two cancer-related genetic biomarkers, HOXC6 and DLX1.
Combined with other clinical factors like total PSA and age, the test produces a likelihood score of discovering clinically significant disease (defined as Gleason Score equal to or more than 7 ).
This provides your urologist with another important piece of information to consider when recommending whether a biopsy is required and potentially avoid an unnecessary and very painful procedure.
The test has sensitivity of 76 percent but a very high specificity, accurate 98 percent of the time - meaning a false-negative rate of 24 percent, but a false-positive rate of only 2 per cent.
In the U.S., the current price for the SelectMDx test is $500 USD.
PROSTATE BIOPSY
A prostate biopsy is most commonly done by the transrectal method through the rectum.
Ultrasound is usually used to look at the prostate gland and guide the biopsy needle.
However, ultrasound doesn't allow visualization of prostate tumours, so a biopsy might miss the tumour.
Now, it's become possible to instead perform an MRI-guided biopsy.
MRI lets doctors see most prostate tumours and detection of prostate cancer has significantly increased - a 57 per cent improvement.
GLEASON SCORES
The Gleason score is the single most important prognostic indicator for prostate cancer and plays a significant role in treatment planning. This score is based on how aggressive the cancer looks under a microscope.
The pathologist looks at the cancer cells in the prostate and assigns a score on a scale of three to five from two different locations, first the area where the cancer is most obvious and then the next most obvious area of growth. The pathologist then gives each area a score from three to five with a more aggressive appearance receiving a higher score.
The scores are added together to come up with an overall score between 6 and 10.
For example, the most common grade of the cells in a tissue sample may be grade 3 cells, followed by grade 4 cells in less common areas.
The Gleason score for this sample would be Gleason 3+4=7. Cancers will score 6 or more. A score of 7 means the cancer is intermediate, and a higher score (8 to 10) means the cancer is more likely to grow and spread.
Someone with a Gleason score of 7 that comes from adding 3 + 4 has a less aggressive cancer than someone with a Gleason score of 7 that comes from adding 4 + 3 because the person with a 4 + 3 =7 grade has more grade 4 cells than grade 3 cells.
The lowest Gleason score is 6, which is a low-grade cancer.
A Gleason score of 7 is a medium-grade cancer, and a score of 8, 9, or 10 is a high-grade more aggressive cancer.
Doctors look at the Gleason score in addition to stage to help plan treatment.
For example, Active Surveillance or Watchful Waiting) may be an option for someone with a small, localized tumour, low PSA level, and a Gleason score of 6 or 7.
People with a higher Gleason score may need more aggressive treatment.
Gleason scoring by pathologists is a labour-intensive, error-prone subjective process suffering from observer variability, with reported Gleason score discordance ranging from 30 percent to 53 per cent.
Increased consistency and accuracy of Gleason grading lies in the field of Artificial Intelligence, where Computer-aided Gleason grading has been developed to assign Gleason grades in an automatic and reproducible manner.
AI assistance improves tumour detection, review time, and inter-pathologist agreement.
CANCER STAGING
The stage of the cancer is done by the T, N, and M classifications.
T is tumour status, the size of the cancer in the prostate, N is any spread to the regional lymph nodes and M is any distant metastatic spread.
Staging also includes the PSA level and Gleason Grade Group.
Stage I and Stage II: The cancer is found only in the prostate.
Stage III: The cancer has broken through the capsule of the prostate gland and is locally advanced outside the prostate gland.
Stage IV: The cancer has spread to lymph nodes and/or other parts of the body.
After the results of the biopsy are back, the next step is to sit down with a urologist who specializes in prostate cancer or an oncologist, or preferably, both, to discuss the course of action.
Decision making on treatment (or none, just Active Surveillance or Watchful Waiting) is subtly much more complicated than people realize. Some urologists will automatically push for surgery - “If you have a hammer, everything looks like a nail.”
Since the advent of PSA screening, there has been a lot of overly aggressive treatment, with many negative prostate biopsies, surgeries, and radical prostatectomies resulting in high incidences of total incontinence (Depends!) and total impotence (penile implants!).
It is estimated that between 50 and 100 men undergo unnecessary treatment, surgery and/or radiation, for every life saved.
Consult a urologist specializing in prostate cancer or an oncologist, or better yet, both, before deciding on a course of treatment.
WAIT AND WATCH
Thirty years after it began, a 2019 landmark study, published in the New England Journal of Medicine, that followed 690 Swedish men since they were diagnosed with localized prostate cancer, showed that the disease will not cause harm to the majority of men who have it, and that aggressive treatment is warranted only for men with a high risk of spread.
Half of the men had their prostates removed to get rid of the cancer, and half were put on “Active Surveillance."
Of those who died, 77 per cent died of something other than prostate cancer.
According to the study, those men who had a Radical Prostatectomy at the start of the study lived an average of 2.9 years longer than men who got no therapy.
But 45 per cent of men treated with surgery regretted, often bitterly, their prostate cancer surgery afterwards.
Over-treatment is an issue because Radical Prostatectomy and similar therapies often cause permanent side effects, most commonly total impotence and urinary incontinence.
In Sweden today, 80 percent of men with newly diagnosed prostate cancer are not treated, but “Actively Surveilled,” to make sure their tumour is not becoming more dangerous.
“Active Surveillance” includes regular checkups, whereas with “Watchful Waiting,” follow-ups were deferred until a man had symptoms. The majority who are diagnosed today are diagnosed very early from PSA detection and have usually low-risk disease.
They will very likely be over-treated if they are treated immediately.
Gleason 6 disease almost never develops into aggressive cancer requiring treatment and patients with Gleason 6 cancer can avoid treatment such as Surgery and Radiation, and their side effects
Most men with Gleason 7 cancers will not die from the cancer, but rather, with it.
Watchful Waiting - means follow-ups are deferred until a man has symptoms.
Active Surveillance - aims to avoid unnecessary treatment of harmless cancers while still providing timely treatment for men who need it.
Active surveillance formerly involved having regular PSA tests, MRI scans and sometimes biopsies to watch for any signs of progression.
Now PCA3 levels can be followed to tell us how aggressive the cancer is and whether it is progressing.
Men undergoing active surveillance will have delayed any treatment-related side effects, and those who eventually need treatment will be reassured that it was necessary.
I am 76 and if I were diagnosed with localized Gleason 7 prostate cancer, I would opt for Active Surveillance.
Active treatment of prostate cancer will be another topic.