Prostate Cancer

Ulka: The hereditary cancers that are associated with breast cancer and ovarian cancer are also associated with an increased risk of prostate cancer. Routinely, people think that just because the females in the family had cancers that it won't affect them, and that is a completely wrong assumption.

Brent: That I am your host for today.

Brent: Dr. Vaishampayan is a medical oncologist at the University of Michigan, and she has spent her career studying prostate cancer. More than 20% of men will get prostate cancer during their life. So we all want to have the information we need about how to screen for it, because if we catch it early, the outcomes are really good, and what the treatment looks like if it does show up in our lives.

Brent: This is a really good primer on prostate cancer. I feel much smarter and more well-prepared for it, and I hope you do as well.

Brent: Dr. Ulka, hi and welcome to the show.

Ulka: Thank you.

Brent: So the topic of the conversation today is prostate cancer. When my grandfather died, he had prostate cancer, though he did not die of it. I'm a 43-year-old male, so it's something that I'm thinking about. I'm looking forward to diving in. Before we get into the basics of all things prostate cancer, can you share a little bit about your background and bio?

Ulka: I'm a physician and medical oncologist. My research focus, both in clinical trials and clinical practice, is centered on prostate cancer. Thank you for having me on the show. It's a pleasure to be here and raise awareness about prostate cancer, because if this disease is found early, it can make a big impact on cure and long-term remission rates.

Ulka: I'm at the University of Michigan in Ann Arbor. I have published on the topic of prostate cancer and am looking forward to taking questions and discussing the topic.

Brent: Wonderful. Let's start with the basics. What is the prostate, and what is its function?

Ulka: It's a gland in the body that surrounds the bladder neck where it joins the urethra, which carries urine out of the bladder. It is present only in men. Prostate cancer is one of the most common cancers in American men, as well as worldwide—including in the Caribbean and South America (such as Brazil and Argentina), where prostate cancer incidence is very high.

Ulka: The gland releases secretions, but it is not essential to the body. Removing it for cancer or other reasons does not cause a major impact; we don't miss the gland, so to speak. In a nutshell, that is the prostate, and its most common pathology tends to be benign enlargement.

Ulka: With age, men experience gradual benign enlargement. It is very common for people to notice that their urine flow has slowed down because the enlarged prostate is pressing on the urethra.

Brent: Why not just remove everybody's prostate? If it's such a common cancer and acts somewhat like an appendix, why isn't it routinely removed? I assume there is a good reason why we don't do that.

Ulka: First of all, the surgery carries potential complications. Due to its location, a number of critical nerves and the bladder can be affected. The appendix has zero function and is located where it can be removed easily without issues, yet we still don't perform surgery unless there is a specific problem with it.

Ulka: The same principle applies to the prostate, with additional potential risks inherent to surgery due to its location.

Brent: So the prostate is responsible for men complaining about waking up to urinate at night, frequent urination, or a weaker stream than when they were younger. When does this enlargement typically begin?

Ulka: It is a continuous process, but usually starts around 45 to 50 years of age. It varies by individual: some men have an enlarged prostate by age 55, while others show no enlargement even at age 90. Generally, benign prostatic hyperplasia is a condition associated with aging.

Brent: How common is prostate cancer among men?

Ulka: If you screen men over the age of 50 with a PSA blood test and a digital rectal exam, the incidence is about 1 in 4. Around 25% of that cohort will have some degree of prostate cancer, so it is very common when actively looked for.

Ulka: Overall, between 15% and 20% of US men over age 50 or 60 will have it.

Brent: So there is a PSA blood test and a rectal exam. Is there a two-in-one screening done during a colonoscopy, or is colon cancer screening entirely separate?

Ulka: That is separate. Colonoscopies are specifically for colon cancer, alongside other non-invasive options like blood or stool tests. For prostate cancer, the simplest screening method is the PSA (prostate-specific antigen) blood test, where a level usually above 4.0 ng/mL raises suspicion of cancer.

Ulka: There are caveats depending on individual risk factors where a biopsy might be suggested at a lower PSA level.

Brent: When you mentioned a rectal exam, were you referring to a biopsy or a physical examination?

Ulka: That refers to a clinical examination in the clinic where the physician palpates the prostate through the rectum to check for hard masses or lumps.

Brent: Feeling directly with a gloved finger—uncomfortable, but manageable. Are there stool tests for prostate cancer similar to those for colon cancer?

Ulka: No, there are not. The prostate does not connect to the colon or rectum, so stool testing is not effective for prostate cancer.

Brent: Regarding PSA testing, there is controversy about screening too early or too frequently. Could you shed light on why that controversy exists?

Ulka: For a period, the US Preventive Services Task Force recommended against routine PSA screening, or advised a balanced discussion with patients due to potential harms from unnecessary biopsies. This was based on studies suggesting that screening primarily detected low-grade, slow-growing cancers.

Ulka: However, after screening rates dropped, clinicians observed a higher percentage of patients presenting with advanced prostate cancer, missing the window for early curative intervention. Consequently, updated task force recommendations support considering screening for men starting at age 50.

Ulka: Individuals with a strong family history, hereditary risk (such as BRCA gene mutations associated with breast or ovarian cancer), or those taking medications for BPH may need to begin screening earlier. For most men, starting around age 45 to 50 is appropriate.

Ulka: You know, it's important to do that.

Brent: What is the rationale against testing at age 35 or 40? What are the drawbacks of checking PSA levels below the recommended screening age?

Ulka: The PSA is a sensitive test, meaning it frequently flags potential issues, but it is non-specific. Minor inflammation, urinary tract infections, or localized skin infections can elevate PSA levels, leading to false alarms.

Ulka: An elevated result often leads to a biopsy, which carries risks of bleeding, infection, and emotional stress. These factors explain why routine PSA screening is not recommended for everyone at a young age.

Brent: If a 35-year-old gets a PSA test that comes back elevated due to benign inflammation, they experience substantial anxiety about a potential cancer diagnosis.

Brent: The next diagnostic step is a biopsy to extract and evaluate tissue, which involves physical discomfort and clinical risk.

Brent: If the biopsy is negative, the patient underwent physical and psychological strain without benefit. That balance of risk is why guidelines recommend waiting unless an individual is high-risk.

Ulka: Additionally, the probability of detecting prostate cancer at that age is extremely low, making routine testing clinically unjustified.

Brent: For an individual who happens to be the rare case caught early, screening is invaluable regardless of population-level statistics. Is prostate cancer less common at younger ages compared to colon cancer?

Ulka: Yes. Both prostate and colon cancers primarily affect older demographics, with the median age of diagnosis for prostate cancer being between 65 and 70.

Brent: What are the primary risk factors and known causes of prostate cancer?

Ulka: There is no single definitive cause. Age is the main risk factor. Hereditary mutations associated with breast and ovarian cancer—specifically BRCA1 and BRCA2 genes—also elevate the risk of prostate cancer in men. People often mistakenly assume that female family history of cancer does not affect male relatives.

Ulka: That assumption is incorrect. If BRCA or related genetic mutations are present in a family, male relatives should pursue genetic testing and screening.

Brent: Apart from genetics, what role do lifestyle risk factors play?

Ulka: Some observational evidence suggests that a healthy diet and regular exercise may lower risk. For example, migration studies show that men moving from Japan to the US gradually assume an incidence rate closer to the higher US average, indicating environmental or dietary influences.

Ulka: However, no direct causal link has been established between a specific diet or lifestyle factor and prostate cancer development.

Brent: So the connection to diet and exercise is weaker compared to other cancers, though population shifts hint at environmental factors. What symptoms should someone look out for if they haven't been screened?

Brent: But when people are concerned and go in and find out they have it.

Ulka: Ideally, prostate cancer is detected while a patient is asymptomatic. Obstructive urinary symptoms—such as frequent nighttime urination, difficulty initiating a stream, or a weak stream—should be evaluated by a physician with a PSA test to rule out malignancy.

Ulka: Some patients present with advanced disease involving metastasis. Bones are the most common site of metastasis, followed by lymph nodes, which can obstruct urine flow from the kidneys and impair renal function. Spinal involvement can lead to nerve compression or localized bone pain.

Brent: Most cases are identified in asymptomatic patients through routine screening.

Ulka: Early asymptomatic detection offers the best opportunity for successful treatment.

Brent: How aggressive is prostate cancer, and how quickly does it progress?

Ulka: Aggressiveness is evaluated using grade, stage, and PSA levels. Higher PSA levels correlate with more advanced disease. A PSA above 4.0 ng/mL is generally abnormal, though lower thresholds (such as 2.5 ng/mL) are applied for patients taking BPH medications that shrink the prostate or for African American men who face higher statistical risk.

Ulka: The rate of change in PSA over time, known as PSA velocity, is also an important marker. Histological aggressiveness is determined microscopic evaluation using the Gleason grading system.

Ulka: A Gleason score of 6 or lower indicates low-grade cancer, 7 indicates intermediate grade, and 8 to 10 signifies high-grade or aggressive prostate cancer. Staging determines anatomical spread—whether the cancer remains localized within the prostate or has extended to lymph nodes or bone.

Ulka: That is what the stage, implies.

Brent: Is grading a subjective interpretation by the pathologist, or is it based on objective structural criteria under the microscope?

Ulka: The Gleason system is highly standardized and reproducible across institutions, so inter-observer variation among pathologists is minimal.

Brent: Pathologists evaluate cellular architecture against established diagnostic criteria to assign a grade.

Ulka: Correct. The score is based on a point-in-time tissue sample rather than a direct measurement of dynamic growth rates.

Brent: Prostate cancer has a reputation for slow progression, leading many men to die with it rather than from it, unlike more aggressive malignancies like pancreatic cancer. How quickly does the disease typically progress?

Ulka: Approximately one-third of prostate cancer cases are aggressive, and 10% to 15% of patients present with metastatic disease at diagnosis. In an otherwise healthy individual, metastatic prostate cancer is significant and frequently becomes the primary cause of mortality.

Ulka: While the idea that prostate cancer is non-fatal holds true for a subset of low-risk patients, at least half of all cases are clinically significant and require active treatment to prolong survival.

Brent: So the perception that prostate cancer is always indolent is inaccurate.

Ulka: That assumption applies to some cases, but because the disease is so widespread, a large absolute number of aggressive cases occur.

Brent: In cases where the disease is aggressive, is that due to tumor biology, delayed detection, or a combination of both?

Ulka: It is a combination. Among patients placed on active surveillance for initial low-grade disease, roughly one-third eventually reclassify with clinically significant disease that requires definitive intervention like surgery or radiation therapy.

Brent: So a tumor can be classified as low-grade, placed on surveillance, and later transition to higher-grade behavior. Do we understand why that shift happens?

Ulka: It remains unclear whether a higher-grade clone was present initially in a small volume and expanded over time, or if true biological progression occurred. Genomic testing performed on biopsy tissue can now help predict the likelihood of progression with greater accuracy.

Ulka: AI applications incorporating multi-parametric prognostic data directly from pathology slides are further improving our ability to predict disease trajectory.

Brent: To summarize screening: men should discuss PSA blood testing and digital rectal exams starting around age 45 or 50. How frequently should screening recur once initiated?

Ulka: Screening is typically performed annually or every two years. If a first-degree relative was diagnosed at an early age—for instance, a father diagnosed at age 50—screening should begin 10 years earlier than the index case.

Brent: If diagnosed with low-grade disease and placed on active surveillance, does monitoring differ significantly from routine screening?

Ulka: Surveillance includes more frequent PSA checks and typically a confirmatory repeat biopsy within 6 to 12 months.

Brent: So repeat biopsies are integrated into active surveillance protocol.

Ulka: Not continuously every 6 to 12 months, but a second confirmatory biopsy is standard.

Brent: If higher-grade cancer is identified, what are the primary treatment modalities?

Ulka: Options depend on overall patient health. For localized disease in healthy individuals, radical prostatectomy (surgery) or radiation therapy are mainstays. For high-risk localized disease with markedly elevated PSA or high Gleason scores, a PSMA PET scan is recommended to detect early metastatic disease outside the prostate.

Ulka: Identifying extraprostatic spread guides management. Surgery or radiation remain the standard primary interventions for localized disease.

Brent: For localized disease, surgery aims to remove the entire prostate gland to excise all malignant tissue. Is radiation administered post-operatively as standard practice, or only under specific indications?

Ulka: Adjuvant radiation is not always required. Following complete surgical removal, serum PSA should drop to undetectable levels within a few weeks. Patients are monitored with periodic PSA tests. If PSA remains detectable or rises post-operatively, secondary therapy with radiation is indicated.

Brent: Is chemotherapy utilized in prostate cancer treatment?

Ulka: Chemotherapy is reserved for advanced or metastatic disease. High-grade disease with lymph node involvement may warrant chemotherapy, though androgen deprivation therapy (hormone therapy via injectable or oral agents) is the primary systemic treatment.

Brent: What are the physiological side effects of prostatectomy?

Ulka: Complications stem from surgical manipulation of adjacent neurovascular structures rather than organ loss itself. Potential side effects include stress urinary incontinence and erectile dysfunction, depending on nerve preservation during surgery.

Brent: So functional side effects relate directly to the surgical procedure and anatomical proximity.

Ulka: These complications do not affect every patient. While transient urinary and erectile dysfunction are common immediately post-op, approximately 80% of surgical patients recover baseline functional status over time.

Brent: Are overall incidence rates of prostate cancer increasing in the population?

Ulka: True baseline incidence has remained relatively stable. A temporary rise in advanced presentations occurred when routine screening was halted, whereas initial adoption of PSA screening years ago produced a sharp rise in detected early-stage cases.

Brent: So diagnostic precision and early detection trends show positive long-term direction.

Ulka: The same.

Brent: Overall disease mortality has declined over time due to earlier diagnosis.

Ulka: Yes, overall mortality dropped significantly following the widespread adoption of PSA screening.

Brent: What emerging therapeutic developments in prostate cancer treatment are most promising?

Ulka: Advanced stage therapies are progressing rapidly. Treatments validated in late-stage metastatic disease are gradually moved into earlier settings to improve cure rates and extension of life. A decade ago, single-agent therapy was standard for advanced disease at diagnosis.

Ulka: Today, combination triplet regimens nearly double median survival expectancies for advanced cases.

Brent: Does that include immunotherapy?

Ulka: Immunotherapies have shown limited efficacy in prostate cancer. The main advances involve novel targeted hormonal agents that provide prolonged disease control, along with radiopharmaceutical therapies.

Ulka: Radioligand therapies attach radioactive isotopes to PSMA-targeting ligands, delivering targeted radiation directly to prostate cancer cells. Radiopharmaceutical approaches represent a significant transformation in management.

Brent: What is the perspective on artificial intelligence integration in oncology practice?

Ulka: Overtreatment of indolent disease remains a major clinical concern. AI models offer immense value in prognostic stratification by integrating complex histopathological, genomic, and clinical parameters beyond standard stage, grade, and PSA to distinguish indolent from aggressive tumors.

Ulka: Improved prognostic precision allows clinicians to safely withhold unnecessary interventions for low-risk patients.

Brent: By overtreatment, you mean performing prostatectomies on patients with non-lethal tumors who would not have died from the disease.

Ulka: Yes, as well as prolonged androgen deprivation therapy. Long-term hormone therapy increases risks for cardiovascular disease, metabolic syndrome, osteoporosis, fractures, and cognitive decline or dementia.

Ulka: Avoiding unneeded systemic treatments prevents these therapy-induced morbidities.

Brent: If treatment side effects exceed disease risks, intervention was unwarranted. What proportion of treated patients fall into that category?

Ulka: It is an underreported issue. Estimated conservatively, at least 5% of patients experience significant treatment-related complications or reduced overall longevity due to side effects when their underlying cancer was non-lethal.

Brent: In about 5% of cases, net clinical benefit is negative due to treatment side effects.

Ulka: Correct; treatment burden in those instances compromised overall quality or length of life.

Brent: What fundamental advice do you give to family members regarding screening?

Ulka: I recommend obtaining a baseline PSA test at age 45. If normal, routine screening every two years is a reasonable protocol.

Brent: So age 45 is your recommended starting threshold in the absence of risk factors.

Ulka: Yes, assuming no known family history. If a familial risk exists, screening should start 10 years earlier than the youngest affected relative's diagnosis age.

Brent: Whichever comes first. Are there any other key points to cover for prostate cancer 101?

Ulka: The key message is awareness and screening. It is a straightforward blood test, far less invasive than procedures like colonoscopies. Every man should initiate screening between ages 45 and 50.

Brent: It pairs naturally with routine annual preventive health care, alongside lipid panels, blood glucose, A1C, and hormone evaluations.

Brent: Thank you so much for joining us and for the important work you do.

Ulka: Thank you. It was a pleasure.

Brent: Death Clock is recorded in San Francisco, California. Music by Patrick. Produced by Patrick Gudino and hosted by yours truly, Brent Franson.