Prostate Cancer

What is Prostate Cancer?

Prostate cancer is the most common type of cancer diagnosed in men around the world and is the fifth leading cause of cancer-related death in men. Each year, over 1.4 million new cases are diagnosed, leading to 375,000 deaths globally. In fact, prostate cancer is the most common cancer diagnosed in over half of all countries (112 out of 185).

The good news is, most prostate cancers tend to grow slowly and are low-grade, meaning they are at a lower risk of spreading and being aggressive.

For most people, prostate cancer does not show any early symptoms. However, as it progresses, symptoms such as fatigue (caused by anemia or low red blood cells), bone pain, paralysis from cancer spreading to the spine, and kidney failure due to blockage of the urine tubes can occur.

Diagnosis of prostate cancer usually involves testing for prostate-specific antigen (PSA) – a substance produced by your prostate that can be measured with a blood test, and taking tissue samples from the prostate guided by an ultrasound inserted via the rectum. But using PSA tests for widespread screening is still debated among experts.

There are more modern ways to diagnose prostate cancer, like measuring the amount of free and total PSA, PCA3 urine testing, scoring the Prostate Health Index, the”4K” test, exosome testing, analyzing the genetic makeup of the problem tissue, MRI imaging, PIRADS scoring, and MRI-ultrasound guided biopsies.

When prostate cancer is only found in the prostate, it can potentially be cured. On the other hand, when it has spread to the bones or beyond the prostate, there are various treatment options available, including pain medications, drugs that prevent bone breakdown, hormonal treatment, chemotherapy, radiation, immunotherapy and other targeted therapies. How patients respond to these treatments depends on their age, other health issues, the biological characteristics of the cancer, and how far the cancer has spread.

What Causes Prostate Cancer?

Your chances of getting prostate cancer go up with age, obesity, ethnicity, and family history. While the overall occurrences increase as you age, the severity tends to decrease.

Various factors can increase your risk of getting prostate cancer, like being a man, older age, having relatives with prostate cancer, being taller, obesity, high blood pressure, lack of exercise, high testosterone levels, exposure to Agent Orange, and ethnicity.

Medications like finasteride and dutasteride, which are called 5 Alpha-Reductase Inhibitors, can lower the chance of getting a less serious type of prostate cancer, but they don’t really help against serious types of the disease. They also don’t improve how long you live with the illness. These drugs can also lower the levels of something called prostate-specific antigen (PSA) by about 50%, so anybody monitoring their PSA levels needs to keep this in mind.

The exact cause of prostate cancer isn’t known, but your genes definitely play a role. Your genetic background, ethnicity and family history help decide how likely you are to get prostate cancer. Patients with hereditary prostate cancer, which is passed down from generation to generation, usually get sick at an earlier age, their condition worsens quicker, and their disease is likely to be more severe and come back after surgery.

Black men in the US are more likely to get prostate cancer than white or Hispanic men, and the disease is more deadly in blacks. Hispanic men, on the other hand, are one-third less likely to get prostate cancer and die from it compared to non-Hispanic whites.

Certain types of diets have been associated with prostate cancer. Foods common in the typical Western diet can increase the risk, for example, diets high in fats and dairy products. There’s limited evidence for any association between fats or carbohydrates and this disease. However, a diet that is high in unsaturated fats, like lard, can increase the progression of prostate cancer. Alcohol doesn’t seem to have a significant impact on the risk. Contrarily, moderate red wine consumption could be beneficial.

Certain vitamins and diets rich in calcium are associated with a more advanced stage of prostate cancer. Consuming whole milk after being diagnosed with prostate cancer has also been linked to a higher risk of the disease recurring, especially in overweight men. On the other hand, those having low levels of vitamin D may have higher chances of getting prostate cancer, suggesting that vitamin D supplements could be a beneficial addition to the diets of those deficient in the vitamin.

Certain chemicals and medications can also impact your likelihood of getting prostate cancer. Medications such as statins, metformin, and NSAIDs, especially those that suppress COX-2, an enzyme involved in inflammation, may lower your risk. Interestingly, regular aspirin usage, which is common among an estimated 23.7 million men, seems to reduce the risk.

Your sexual activity could factor into your risk for prostate cancer. Having many sexual partners or starting sexual activity early in life increases the risk. However, frequent ejaculation may reduce the overall risk.

Certain infections like chlamydia, gonorrhea, or syphilis could increase your risk of developing prostate cancer. There’s also some suggestion that the Human Papilloma Virus (HPV) could be linked to the disease, but the evidence is unclear.

A long-standing question is whether vasectomy, a procedure for male sterilization or permanent birth control, is associated with increased prostate cancer risk. The relationship between the two is not clear yet, as studies have produced conflicting results.

Risk Factors and Frequency for Prostate Cancer

Prostate cancer is the most commonly diagnosed organ cancer in men and is the second leading cause of cancer death among men in the United States, following lung cancer. Despite this, the American Cancer Society states that a relatively low number of patients with prostate cancer die from the disease. In 2022, it’s estimated that there will be 268,490 new cases and around 34,500 deaths due to prostate cancer in the U.S. alone.

• Prostate cancer is more common in developed countries.
• The 5-year survival rate in the U.S. is 99%.
• The number of cases has increased over the years, but the death rate has slowly been decreasing since the introduction of PSA testing in 1992.
• Most cases of prostate cancer occur in men over the age of 50, but it can be very aggressive when it occurs in younger men.

In the U.S., prostate cancer is much more common in African American men, occurring at more than double the rate of the general population. Asian and Hispanic men are less likely than white men to have this type of cancer.

The World Health Organization reports that the highest incidence of prostate cancer is seen in Guadaloupe, Martinique, Ireland, Barbados, St. Lucia, Estonia, Puerto Rico, France, Sweden, and the Bahamas. The lowest incidence is reported in Asian countries.

The highest death rates from prostate cancer are seen in Grenada, Zimbabwe, Barbados, Haiti, Zambia, Jamaica, Trinidad/Tobago, Bahamas, the Dominican Republic, St. Lucia, and the Ivory Coast. The lowest mortality rate from prostate cancer is in Nepal and Yemen.

Prostate cancer is more common in developed countries, but less common in Asian men living in Asia. However, when Asian people migrate to the U.S., their incidence of prostate cancer increases, but it is still lower than the overall risk for the general population of American men.

• In Europe, prostate cancer is the third most frequently diagnosed cancer, following breast and colorectal cancers.
• In the U.K., it’s the second most common cause of cancer death in men, following lung cancer.

The World Health Organization also states that Sweden, where few PSA tests are done and the treatment approach to prostate cancer is less aggressive, has a mortality rate that is 2.5 times the rate in the U.S. This makes prostate cancer the leading cause of cancer death in Swedish men, surpassing even lung cancer.

It’s estimated that over 80% of men will develop prostate cancer by the time they are 80 years old, though this is typically a slow-growing, less aggressive form of the disease that doesn’t usually impact their survival. As of 2015, there were about 3 million prostate cancer survivors in the U.S., and this is expected to increase to 4 million by 2025.

While prostate cancer is rare in men under 45, representing just 0.5% of all new cases, the incidence of this disease is increasing globally. This is likely due to increased screenings, previously undiagnosed cases, and an increasing number of contributing risk factors like obesity, physical inactivity, HPV infections, and environmental carcinogenic exposures.

According to the National Cancer Institute, 11.6% of all American men will be diagnosed with clinically significant prostate cancer in their lifetime. In 2020, there were 174,650 new cases and 31,620 deaths from prostate cancer in the U.S. It’s estimated there will be 268,490 new cases and 34,500 deaths from prostate cancer in the U.S. in 2022.

• Most new cases are diagnosed in men between 65 and 74 years old, with the median age of diagnosis being 66 years.
• At present, there are 3,085,209 men living with prostate cancer in the U.S.
• The overall risk of a man dying from prostate cancer is 2.6%, or 1 in 39.
• The median age of death for those dying of prostate cancer is 80 years.

Most men diagnosed with prostate cancer will eventually die from other causes, with about 20% of cases resulting in death due to cardiovascular disease. The state with the highest incidence and mortality rate from prostate cancer is Kentucky.

Since 2012, routine PSA screenings have not been recommended by the United States Preventive Services Task Force. This decision has led to several changes in the clinical and pathological characteristics of prostate cancer. For instance, there has been a decrease in the diagnosed incidence of low-grade prostate cancer, an increase in intermediate and high-grade disease, and an increase in cases must be identified with higher PSA levels over 10 ng/ml or even over 20 ng/ml. Additionally, the incidence of seminal vesicle invasion, lymph node involvement, and positive surgical margins also increased after 2012.

Mortality statistics for prostate cancer vary by ethnicity, with African Americans having the highest incidence and mortality rates. According to the American Cancer Society, prostate cancer is the most common organ cancer in African American men, accounting for about 37% of all cancers in this population and 17% of all cancer-related deaths. This incidence is 72% higher in African Americans than in Whites, and the overall lifetime risk of developing or dying from prostate cancer is 1:6 in African Americans compared to 1:8 in Whites.

• Black men have a mortality rate of 42.0 per 100,000 people.
• The general population has a mortality rate of 20.1 per 100,000 people.
• The mortality rate for American Indians is 19.4 per 100,000 people.
• The mortality rate for White men is 18.7 per 100,000 people.
• The mortality rate for Hispanic men is 16.5 per 100,000 people.
• The mortality rate for Asian men is 8.8 per 100,000 people.

Signs and Symptoms of Prostate Cancer

Prostate cancer in its early stages often doesn’t cause any symptoms. However, when it does, these symptoms can resemble those of a noncancerous condition called benign prostatic hyperplasia. These symptoms include an increased urge to urinate, waking up at night to urinate, difficulty beginning and keeping a steady flow of urine, blood in the urine, and painful urination.

Prostate cancer may also result in sexual problems, such as difficulty getting or keeping an erection, and pain during ejaculation.

Several factors can increase the risk of developing prostate cancer. A family history of prostate cancer, being of African American ethnicity, and certain inherited gene mutations (like BRCA1 or BRCA2) can all raise your risk. These gene mutations are often suspected if there are cases of early-onset breast cancer in female family members or relatives. If someone in your family has had colon cancer, it might indicate the presence of Lynch Syndrome, which is linked with prostate cancer and certain other cancers that affect the urinary tract.

The most common physical sign of prostate cancer is a hard lump or nodule that can be felt in the prostate during a rectal exam. There might also be an uneven texture or an overall hardness. A very firm prostate can suggest advanced disease.

If prostate cancer spreads, it can cause other symptoms. It might affect the spinal cord, leading to tingling sensations, weakness or pain in the legs, paralysis, and loss of bladder or bowel control. When prostate cancer metastasizes or spreads to other parts of the body, it often causes severe bone pain, especially in the back, pelvis, hips or ribs. If it spreads to the thigh bone, it usually affects the part of the bone closest to the body.

A note of caution: these symptoms can also be caused by conditions other than prostate cancer. If you’re experiencing any of these symptoms and are concerned, you should seek medical advice.

Testing for Prostate Cancer

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Treatment Options for Prostate Cancer

The first step when dealing with prostate cancer is determining if treatment is necessary. Prostate cancer, particularly low-grade tumors, often grows at such a slow pace that treatment may not be required, especially in older patients or those with other serious medical conditions that could decrease their life expectancy to less than 10 years.

Active Surveillance

For many mild cases, active surveillance is now an option. This means the patient will regularly undergo PSA (a blood test that screens for prostate cancer) testing and must have an additional biopsy between 12 to 18 months after the initial diagnosis. Active surveillance is generally appropriate for men with low-grade prostate cancer and small tumors. Some intermediate-grade tumors may also qualify. The use of active surveillance for select, lower-risk, intermediate-grade prostate cancers is still being debated, but it can be a reasonable approach for specific cases. Genomic testing (analysis of genes related to cancer) and tissue-based biomarkers (substances that can indicate cancer) can help clarify the risk of tumor progression and aggressiveness in these borderline cases.

The aim of close monitoring is to identify the roughly 25% of patients who will show significant increases in PSA levels, clinical progression, or an upgrade to a higher Gleason scale score (a system that predicts the aggressiveness of prostate cancer). This may indicate the cancer is becoming more aggressive, and at this point, definitive treatment can be given. At the same time, most patients can safely avoid the costs, inconvenience, side effects, and complications of definitive curative therapy.

No specific biomarker or bioassay (a test that measures specific substances in the body) has been tested and validated for use in active surveillance protocols for prostate cancer. Because of these limitations of the PSA and PSA density measurements, serial prostatic MRIs (Magnetic Resonance Imaging which gives pictures of the prostate) and an appropriate bioassay might eventually prove a suitable alternative to repeated biopsies every 18 to 24 months.

The key is to consider the stage of the cancer, Gleason score and PSA level, as well as individual patient preferences, overall health, other medical conditions, quality of life, and age. Family history alone has not shown to be a significant risk factor.

Active surveillance is not widely used yet, despite its suitability for many low-risk prostate cancer patients.

The use of imaging methods in active surveillance patients may significantly reduce the need for repeated biopsies. However, even negative serial MRI scans and stable PSA levels could not guarantee a lack of progression which occurs in 14% of such patients. Therefore, a follow-up biopsy is recommended every three years regardless of other findings.

In localized disease, it’s important to know that the choice of treatment makes very little difference in survival over the next ten years for most patients. Given this, definitive therapy should only be offered to those patients who are reasonably expected to live another ten years or have a significant risk of progression.

Focal Ablation Therapy is a new direction in treatment that uses different types of energy (including microwave, cryotherapy, laser, high-intensity focused ultrasound) to treat a localized malignant prostatic lesion. There are still questions about the long-term effectiveness of this approach and which technologies will ultimately provide the best combination of cancer control and minimal side effects. Focal ablative therapies for localized prostate cancer are currently considered investigational in the United States.

Hormone Therapy

Testosterone deprivation or hormone therapy is commonly used in the management of prostate cancer. This therapy can help put the cancer into remission and it remains beneficial for about two years, after which most prostate cancers will eventually regrow.

The most common side effect of hormone therapy is hot flashes in up to 80% of men on hormone therapy. Other symptoms occasionally reported include irritability, anxiety, or heart palpitations. Men who experience hot flashes after starting hormone therapy often report that they tend to decrease in frequency and intensity over time. Hormonal therapy can also lead to reduced bone density, resulting in osteopenia or osteoporosis.

A DEXA scan, a type of x-ray that measures bone density, is recommended for all patients starting hormone therapy and has to be repeated every two years. After the DEXA scan, full bone loss preventive therapy, including calcium and vitamin D supplements along with a bisphosphonate or rank ligand inhibitor (medications that help maintain bone density), is suggested for all patients who have been diagnosed with advanced erosion of bone density.

Skeletal fractures are almost four times more likely after two years of hormone therapy. Prostate cancer patients with fractures face a markedly increased mortality risk, seven times higher than similar patients without fractures.

Lastly, it’s important to remember that every case is different. Patients should have thorough discussions with their healthcare provider to decide on the most suitable course of action based on their individual circumstances.

What else can Prostate Cancer be?

These are some conditions that could be related to prostate health issues:

• Acute bacterial prostatitis (an urgent infection in the prostate)
• Prostatic abscess (a pocket of pus in the prostate)
• Chronic bacterial prostatitis (a long-term infection in the prostate)
• Benign prostatic hyperplasia (an enlarged prostate which isn’t cancerous)
• Nonbacterial prostatitis (prostate inflammation not due to bacteria)
• Tuberculosis of the genitourinary system (a tuberculosis infection affecting the urinary system and genitals)

Surgical Treatment of Prostate Cancer

Radical prostatectomy, a surgical procedure which removes the prostate gland, offers the highest potential for a definitive cure for localized prostate cancer. This could lead to a significant improvement in overall survival, reduce the risk of the cancer spreading to other parts of the body, and in the long term, have more benefits than other treatment options. These benefits are seen most in men younger than 65 at the time of diagnosis. However, this surgery is not advised if the tumor is fixed to surrounding structures or has spread to other parts of the body.

Most of these surgeries are now performed using robotic technology or with minimal invasive techniques. The choice between these approaches does not seem to make a significant difference in side effects or survival rates. The experience and skill of the surgeon is a key factor for successful outcomes, regardless of the method used.

Each patient’s unique circumstances, such as their age, general health, existing urinary control, level of physical activity, existing sexual function, and whether lymph nodes will be removed or nerves will be preserved, all play a role in deciding the best course of treatment. Utilizing Magnetic Resonance Imaging (MRI) scans can be helpful in making these decisions.

The need for a lymph node dissection is based on whether it is likely that the cancer has spread to the lymph nodes. A dissection can provide more certainty and help in further treatment decisions. However, it is not usually necessary in patients with a lower risk of disease. The extent to which the lymph nodes are dissected remains inconclusive, but widespread involvement is likely to reveal a large number of affected nodes.

After a successful radical prostatectomy surgery, the level of a protein called prostate-specific antigen (PSA) in the blood should become undetectable and remain that way. If this does not happen, or if there are still cancerous cells left after surgery, additional treatment with radiation therapy should be considered. This is done based on the belief that the extra radiation may eliminate the small amount of remaining cancer near the prostate. Radiation therapy is also an option if PSA becomes detectable later on, indicating that some cancer that was previously undetectable might now be growing back.

It is important to consider the fact that all remaining cancer may not be within the radiation field. So, radiation should not be considered if there is clear evidence of cancer spread to distant sites in the body. Additionally, some patients may choose to defer radiation therapy until there is a spike in the PSA level or other evidence of disease progression.

Side effects of radical prostatectomy might include sexual problems such as erectile dysfunction, the inability to control urine flow (urinary incontinence), narrowings of the urinary passage (urethral strictures), and increased chances of developing hernias near the groin. Less than 1% of men undergoing these procedures face the risk of death and rates for sexual dysfunction widely varies depending on different factors.

If radiation therapy fails, another prostate surgery might not be possible due to scarring and other complications, but cryotherapy, a treatment technique that freezes and destroys cancer cells, could still be possible.

Cryotherapy, or freezing technology, has been used to kill cancer cells since the 19th century. This technique causes very effective tissue destruction, but has its disadvantages and relies heavily on technology. Cryotherapy faces some challenges such as potential for unintended injury and difficulty monitoring the exact location of the probes and the frozen area. However, these problems have been managed by using advanced technology and strategies like ultrasound imaging.

The likelihood of sexual dysfunction is relatively high with cryotherapy, so this should be discussed with patients before treatment. Though cryotherapy can be a primary treatment option for prostate cancer, it may also be useful as a secondary treatment after unsuccessful radiation therapy. The ability of cryotherapy to control tumors resistant to other therapies makes it quite valuable in certain cases.

What to expect with Prostate Cancer

The European Association of Urology Guidelines suggest that for men in their early 40s, a high prostate-specific antigen (PSA) level, which is a substance made by cells in the prostate gland, above one ng/ml signals a higher risk of prostate cancer in the future. This is backed by several studies. These studies show that a single PSA test of less than 1 ng/ml in a man in his early 40s is a great sign of good prostate health and the man not getting prostate cancer for the next 25 years or so. Conducting a PSA test in this young age group could also help doctors identify the tiny percentage of men who develop very deadly prostate cancer before age 50.

Different tools or models are now available to help predict prostate cancer outcomes and survival percentages after radical prostatectomy, a surgery to remove all of the prostate gland. They typically take into account factors like age, Gleason score which is a system to grade prostate cancer, biopsy results, and PSA level. They may also need other medical data, like the number of positive biopsies and the percentage of tumor involvement.

Prostate cancer can spread directly into the bladder causing fluid-filled swelling in the kidney, also known as hydronephrosis, and eventually lead to kidney failure if both ureters (tubes that connect your kidney and bladder) become blocked. If this occurs, a decision must be made about whether to proceed with treatment. This usually occurs late in the disease. If surgical procedures are not undertaken at this point, kidney failure will occur, which normally occurs slowly and is painless. Surgical removal of the tumor inside the bladder to alleviate the blockage may improve survival temporarily, but typically for just a few months. This is quite a hard and personal decision. It is recommended that patients and families review and discuss the available options and make a decision long before it becomes necessary. Palliative care, which focuses on relieving symptoms and not curing the disease, and hospice services, which focus on serious, life-limiting illness, should be involved at this stage if not already engaged.

While having a positive tissue biopsy is always preferred before treatment, there are cases where it may not be practical or possible. In such cases, MRI imaging and genomic-analysis testing can be used to start prostate cancer treatment if the risk of cancer is high enough, even without absolute confirmation of cancer. These cases are not usual, and patients need to be told about the standard of care and the potential treatment side effects.

Patients diagnosed in America with localized or regional disease experience a 5-year survival rate of almost 100%. While this rate drops significantly to 29% for patients with distant metastases. The most important predictors of patient outcomes are patient age and general health at the time of diagnosis, as well as the cancer stage, pre-therapy PSA level, and Gleason score.

Choosing the treatment method does not significantly affect life expectancy. Life expectancy tables can be found online on various websites.

A study has found urinary levels of a specific substance, Thromboxane B2 (TXB2), associated with aggressive prostate cancer specifically in African American men. However, the reason for this remains unclear.

Lastly, palliative care focuses on treating cancer symptoms and improving the patient’s quality of life. This can involve various treatments including drugs, radiopharmaceuticals, and palliative radiation therapy. It’s important for patients to involve palliative care and hospice services early enough in the disease so they can start assisting the patient when needed, without any unnecessary delays.