For men in the United States, prostate cancer is the most common cancer (excluding skin cancers) and the second leading cause of cancer death.
Prostate cancer increases in frequency as men age, and about 1 in 7 men will be diagnosed with prostate cancer in their lifetime. This cancer affects the prostate, which is a glandular organ that produces secretions for ejaculate fluid located just below the bladder in men.
The natural history of prostate cancer is quite variable because some prostate cancers can be very non-aggressive while others can be quite aggressive. To better characterize a given patient’s prostate cancer, a risk category is typically assigned based on several clinical factors including PSA level, digital rectal examination findings, and highest biopsy Gleason score.
As a pathologist examines the needle biopsy tissue under a microscope, a number value is designated based on the visual appearance (how normal or abnormal) for the most common and second most common type of glands. The sum represents the total Gleason score, which in practice, ranges from Gleason 6 to Gleason 10. For the most part, Gleason 6 prostate cancers are categorized as low risk; Gleason 7, intermediate risk; and Gleason 8, 9 and 10 are grouped together as high risk.
These broad categories have been further defined and subcategorized based on clinical outcomes into five grading groups: Group 1 (Gleason 3+3), Group 2 (Gleason 3+4), Group 3 (Gleason 4+3), Group 4 (Gleason 4+4), Group 5 (Gleason 9 or 10).
Management decisions vary tremendously from surveillance without active treatment to treatments with surgery or radiation based on patient preference, age, life expectancy, other health conditions, prior surgeries, and risk category of your cancer.
Causes and Risk Factors
The most common risk factors for prostate cancer include increasing age, African ancestry and family history in a first degree relative. Inherited genetic mutations in the BRCA cancer gene, which is associated with ovarian and breast cancer in women, also predispose men to prostate cancer.
When to Speak with a Urologist about Prostate Cancer
You should talk to a Urologist about prostate cancer following diagnosis with a prostate needle biopsy.
What to Expect when Seeking Treatment
In addition to a history and physical examination with digital rectal exam, initial assessment involves imaging, testing and sometimes referrals to help create your personalized cancer plan. Staging imaging is ordered based on risk category to assess for disease outside of the prostate. This imaging can include a CT scan of the abdomen and pelvic or prostate MRI as well as a whole body bone scan. Genomic testing of the biopsy specimen may be recommended to provide an additional risk assessment (beyond Gleason score) based on the unique gene profile within a given patient’s cancer cells. Referral is usually made to a radiation oncologist to discuss the relative risks and benefits of nonsurgical treatment.
Assuming the cancer is not advanced and confined to the prostate, management decision making often differs based on risk category and is determined during conversations with you and your Urologist as you weigh various risks and benefits of specific approaches. In general, men with limited life expectancy should not undergo treatment as the risks outweigh the benefits.
Men with low-risk prostate cancer are candidates for multiple different therapeutic modalities as well as active surveillance, which does not involve upfront therapy. Active surveillance is often a preferred option because Gleason 6 prostate cancer is very unlikely to spread and cause death. in fact, one study failed to show a single patient who had spread of their cancer in a group of 12,000 men with confirmed Gleason 6 prostate cancer.
There are no universally established criteria to determine active surveillance candidates and active surveillance protocols. Criteria ranges from Gleason 6 prostate cancer restricted to no more than two cores with no core having >50% involvement (also known as very low-risk prostate cancer) to any amount of Gleason 6 prostate cancer. It is also sometimes considered with Gleason 7 cancer. Genomic profiling may be used to help confirm that a given prostate cancer appears low risk genetically. Older men or men with reduced life expectancy and higher grade prostate cancers may also be appropriate for active surveillance.
When Gleason 6 prostate cancer is diagnosed on biopsy, the principal risk is that higher grade prostate cancer may be present that was not identified. There is about a 30% chance that a more aggressive prostate cancer may be present elsewhere in the prostate when traditional biopsy with ultrasound only finds Gleason 6 disease. Active surveillance protocols typically include a confirmatory biopsy following the prostate MRI within one year after diagnosis in addition to repeat PSA checks and repeat biopsies every few years. Prostate MRI followed by targeted biopsy can increase the diagnosis of intermediate- and high-risk prostate cancer by about 18% though still misses about 4% of clinically significant cancers. MRI alone without targeted biopsy will miss about 13% of clinically significant cancers. Repeat biopsy can be triggered by rapid PSA rises. Therapy is triggered by increases in Gleason score on biopsy or patient preference.
The goal of active surveillance is to avoid side effects of prostate cancer treatments such as surgery or radiation while preventing progression, metastasis and death from prostate cancer. Studies have demonstrated that it is quite safe. At 15 years, men on active surveillance have about a 3% chance of dying from prostate cancer and less than a 5% chance of developing metastatic disease. About 1 in 3 men who start active surveillance eventually move on to definitive therapy. Those men that do undergo therapy have a similar risk of prostate cancer recurrence as men who chose surgery or radiation initially.
Men with intermediate risk prostate cancer are typically not appropriate candidates for active surveillance and should pursue treatment. The mainstays of therapy are surgical removal of the entire prostate and pelvic lymph nodes, a procedure called radical prostatectomy typically performed through a minimally invasive robot-assisted approach, or radiation to the prostate combined with injectable hormone therapy to reduce testosterone levels temporarily. Radiation can be performed with multiple different approaches that can be further reviewed with a radiation oncologist. Other possible treatment options include brachytherapy, cryoablation, high-intensity focused ultrasound (HIFU). Although focal therapy such as HIFU is an area of intense research, it is not considered the standard of care currently.
Surgery has several benefits including precise pathological staging, straightforward follow-up with PSA levels, and the ability to offer radiation in the event of a recurrence. Radiation does not offer staging information, post-treatment PSA levels may be of uncertain significance, and it is very unusual to proceed with surgery following radiation in the event of a recurrence. External beam radiation usually involves pretreatment placement of three marker beads into the prostate. Almost daily treatments are conducted over about one month in conjunction with at least six months of hormone therapy that may result in lethargy and other low testosterone symptoms. About 10% of men have long-term bowel or bladder irritability and damage to erections is comparable to after surgery at about 1 year following radiation.
Surgery does appear to have a slight long-term survival benefit over radiation, although cure rates are comparable. Cancer outcomes following surgery vary widely based on the precise variables for a given case, including importantly the results from the final pathology postoperatively. The cancer outcomes following surgery for patient specifically can be estimated online with preoperative variables using the Memorial Sloan Kettering Cancer Center nomogram (https://www.mskcc.org/nomograms/prostate/pre_op).
The primary risks of surgery include urine incontinence or leakage and damage to erections. Urine control improves over the first 12 months following surgery with about 50% of men using more than 1 pad per day at 3 months postoperatively and about 10% of men using more than 1 pad per day beyond 12 months postoperatively. Postoperative erections are related to preoperative function, patient age and nerve-sparing during surgery, and erections also improve over the first 12 months following surgery. For men with these factors in their favor, about 60% are able to have penetrative intercourse beyond 12 months postoperatively. Rare risks associated with surgery include damage to the rectum (<1%), need for a blood transfusion (<1%), development of scar tissue at the base of bladder (<1%).
Men with high risk prostate cancer are candidates for radical prostatectomy or radiation with at least two years of hormone therapy. the same therapeutic modalities as the men with intermediate risk prostate cancer. Hormone therapy alone may be recommended for those men with limited life expectancy and symptoms associated with prostate cancer. It is important to understand that high risk prostate cancer has high rates of recurrence after initial therapy given the aggressive nature of the underlying disease. Consequently multiple treatment steps are often required, such as the use of radiation following surgery, to maximize survival benefit. Additional treatment decisions are guided by pathological findings after surgery and posttreatment PSA monitoring.