#273 ‒ Prostate health: common problems, cancer prevention, screening, treatment, and more | Ted Schaeffer, M.D., Ph.D.
Dr. Ted Schaefer, a leading urologist and prostate cancer oncologist, discusses comprehensive prostate health, covering age-related urinary issues, prostatitis, and the controversial finasteride. He delves into prostate cancer, explaining its pathogenesis, advanced screening methods like PSA and MRI, and evolving treatment strategies including surgery and androgen deprivation therapy.
Deep Dive Analysis
16 Topic Outline
Prostate Gland: Anatomy, Function, and Common Issues
Lower Urinary Tract Symptoms (LUTS) and Management
Pharmacologic and Surgical Treatments for LUTS
HOLEP Surgery for Prostate Enlargement
Prostate Size, Cancer Risk, and Hormonal Influences
Prostatitis and Chronic Pelvic Pain Syndrome
Minimizing Urosepsis Risk in Alzheimer's Patients
Finasteride, DHT, and Post-Finasteride Syndrome
Androgens, Epigenetics, and Prostate Cancer Pathogenesis
Genetic and Non-Genetic Risk Factors for Prostate Cancer
PSA as a Screening Tool: Interpretation and Advanced Testing
MRI and Biopsy Techniques for Prostate Cancer Detection
Interpreting Gleason Scores and Active Surveillance
Treatment Options for Aggressive and Metastatic Prostate Cancer
Evolution of Prostatectomy Techniques and Outcomes
Future of Precision Medicine in Prostate Cancer
9 Key Concepts
Androgen Receptor
A transcription factor located in the cytosol of a cell that, when bound by testosterone or dihydrotestosterone (DHT), undergoes a conformational change allowing it to enter the nucleus and activate specific genes. This process is crucial for prostate development and function.
Dihydrotestosterone (DHT)
A potent androgen converted from testosterone by the 5-alpha reductase enzyme, primarily in hair follicles and prostatic tissue. DHT has a much higher affinity for the androgen receptor (about 10 times more potent) compared to testosterone, leading to stronger effects in these tissues.
Post-Finasteride Syndrome (PFS)
A controversial constellation of symptoms reported by men after taking 5-alpha reductase inhibitors like finasteride. These symptoms can include decreased sex drive, impotence, anejaculation, depression, and changes in affect, sometimes persisting even after stopping the medication.
Luminal-like vs. Basal-like Prostate Cancers
Two general molecular phenotypes of prostate cancer identified through AI-based analysis of transcriptomes. Luminal-like tumors are often localized and more sensitive to androgen suppression, while basal-like tumors are more aggressive, capable of surviving in low-testosterone environments, and more likely to metastasize.
PSA (Prostate-Specific Antigen)
A protein produced by prostate epithelial cells primarily to liquefy semen. A small percentage leaks into the bloodstream, and its measurement in blood serves as a biomarker for prostate health, with elevated levels potentially indicating benign enlargement, inflammation, or cancer.
Free PSA
A form of PSA that floats unbound in the bloodstream, representing fully processed PSA. A higher percentage of free PSA relative to total PSA is generally associated with benign prostate conditions, while a lower percentage can indicate prostate cancer.
PSA Density
The ratio of a man's PSA value to his prostate volume, often determined by ultrasound or MRI. This metric helps discriminate between PSA elevation due to benign prostatic hypertrophy (BPH) and elevation due to prostate cancer, with higher densities indicating increased risk.
Gleason Score
A grading system used by pathologists to describe the aggressiveness of prostate cancer based on the patterns of abnormal glandular development seen in biopsy samples. It is a sum of the most common and second most common patterns observed (e.g., 3+3=6, 4+3=7), with higher scores indicating more aggressive disease.
Pelvic Fascial Sparing Surgery
An advanced robotic prostatectomy technique that involves preserving the fascia (connective tissue) and ligaments surrounding the prostate. This approach aims to minimize damage to nerves for erectile function and muscles for urinary continence, leading to better functional outcomes post-surgery.
10 Questions Answered
The prostate is an exocrine gland in men, part of the reproductive system, located just below the bladder. It produces about 50-60% of the components of semen, aiding in reproduction.
LUTS include weak urinary stream, hesitation or slowness in starting urination, urgency, and increased frequency, often due to prostate enlargement compressing the urethra and thickening the bladder wall.
Initial strategies include behavioral modifications like regulating fluid intake, timing fluid consumption (e.g., not before bed), avoiding natural diuretics like caffeine, and using voiding diaries to track intake and output.
These drugs reduce prostate size by 20-30% over time by blocking the conversion of testosterone to DHT. They also significantly depress PSA levels, reducing them by about half after 1-2 years and by 2.5 times after 5 years, which can mask prostate cancer detection.
Elderly patients with Alzheimer's may not recognize or communicate UTI symptoms, and due to age and reduced immune reserve, a simple UTI can rapidly progress to life-threatening urosepsis. Good hygiene and minimizing catheter dwell time are crucial.
While high testosterone in young men doesn't directly cause prostate cancer, the balance of testosterone to estrogen and epigenetic changes during androgen surges (e.g., puberty) may set the stage for future risk. Prostate cancers that are most likely to kill are often capable of thriving in low testosterone environments.
PSA density (PSA value divided by prostate volume) helps differentiate between benign enlargement and cancer risk, with higher densities indicating greater concern. PSA velocity (rate of PSA increase over time) serves as a warning sign for potential aggressive cancer, even if absolute PSA levels are still low.
MRI, particularly 3T multi-parametric MRI, is now a crucial pre-biopsy step. It helps identify suspicious lesions (PI-RADS scores) with high resolution, allowing for targeted biopsies and reducing the number of unnecessary biopsies while enhancing detection of clinically significant disease.
Gleason 6 is the least aggressive type of prostate cancer, and low-volume cases are generally recommended for active surveillance rather than immediate treatment. Data suggests these cancers have very low lethal potential and rarely metastasize unless they progress to higher grades.
Patients should ask about the urologist's use of pre-biopsy MRI, the pathologist's detailed reporting (e.g., percent pattern 4), the surgeon's practice scope (e.g., prostatectomy-only), and their specific outcomes data for surgical margin rates, urinary continence recovery, and erectile function recovery.
49 Actionable Insights
1. Understand Prostate Cancer Risk Factors
Be aware of key risk factors for prostate cancer: West African ancestry, family history (father, brother, uncle with prostate cancer, especially at a young age), and smoking (linked to more aggressive cancer at a younger age).
2. Avoid 5-alpha Reductase Inhibitors for Hair Loss
Do not use finasteride or dutasteride for hair loss due to the risk of post-finasteride syndrome (decreased sex drive, impotence, anejaculation, depression, potentially permanent) and the significant impact on PSA interpretation, which can mask aggressive prostate cancer. Explore alternatives like hair transplants.
3. Take Ownership of PSA Monitoring
Patients should take ownership of their PSA monitoring, understanding their numbers and trends, and discussing them proactively with their physicians, as early detection using advanced metrics (PSA velocity, density) can be life-saving.
4. Baseline PSA Testing at Age 45
Every man at age 45 should have a baseline PSA test to understand their individual baseline and track changes over time. If PSA is below 1, recheck every 2-4 years.
5. PSA Monitoring with 5-alpha Reductase Inhibitors
If taking finasteride or dutasteride, be aware that PSA levels will decline by about half. It is critical to adjust PSA interpretation accordingly (e.g., multiply by 2) and monitor for any rise, as a rising PSA on these drugs is a strong warning sign of aggressive prostate cancer.
6. Behavioral Modifications for Urinary Symptoms
Educate yourself that increased fluid intake leads to increased urinary output. Regulate what you drink and when you drink it, avoiding large volumes before bed and diuretics like caffeine.
7. Address Constipation for Pelvic Pain
Be aware that constipation and changes in bowel function can contribute to pelvic pain and urinary discomfort due to the anatomical proximity and shared innervation of the rectum and prostate. Maintaining regular bowel habits can help.
8. Managing Nocturia with TED Stockings
For individuals experiencing nighttime urinary frequency (nocturia) and peripheral edema, strongly consider wearing knee-high TED stockings to reduce fluid shifting from extracellular to intravascular space when lying down.
9. Address Sleep Apnea for Nocturia
If experiencing nocturnal urinary frequency, get screened for sleep apnea, as it is a driver of this symptom and treating it can resolve the issue.
10. Low-Dose Desmopressin for Nocturia
For men experiencing nocturia without a clear explanation or enlarged prostate, a very low dose of desmopressin (typically 0.2 milligrams before bed) can have profound effects by acting as a synthetic anti-diuretic hormone.
11. Voiding Diaries for Urinary Issues
If behavioral modifications are insufficient or symptoms are unusual, keep a voiding diary to track fluid intake (timing and volume) and urinary output (timing and volume). This helps identify excessive intake or unusual patterns.
12. Alpha Blockers for Obstructive Urinary Symptoms
If behavioral modifications fail for lower urinary tract symptoms, consider an alpha blocker (e.g., alfuzosin, silodosin). These medications relax smooth muscles in the prostate, theoretically enhancing the diameter of the urethral channel and improving stream strength and emptying.
13. M3 Agonists for Storage Urinary Symptoms
If alpha blockers improve obstructive symptoms but storage symptoms (frequency, urgency) persist, consider an M3 agonist. These relax bladder muscles, significantly impacting urgency and frequency, with fewer neurocognitive side effects than older anti-muscarinics.
14. Surgical Consultation for Persistent Urinary Symptoms
If still bothered by urinary symptoms despite medical management, discuss outpatient surgical procedures with a urologist, as these can offer a long-term fix without continuous medication.
15. HOLEP for Large Prostates
For men with very large prostates (e.g., over 70-80 grams, up to 600 grams) causing urinary symptoms, consider Holmium Laser Enucleation of the Prostate (HOLEP) by an experienced surgeon. This procedure removes the entire inner pulp of the prostate, offering durable relief with minimal bleeding and often no catheter post-procedure.
16. Avoid Less Durable Minimally Invasive Procedures
Be cautious of minimally invasive procedures like Urolift that offer only temporary relief and may cause pain or interfere with future diagnostics (e.g., MRI). These are generally not recommended if more effective, durable options are available.
17. Consider Surgical Options for BPH with Persistent Symptoms
If medications are ineffective or symptoms are severe, consider surgical options like TURP (Transurethral Resection of the Prostate) or HOLEP. Modern TURP uses saline irrigation to reduce complications, and HOLEP is highly effective for large prostates.
18. Small Prostate with Persistent Symptoms: Rule Out Other Causes
If profound urinary symptoms persist with a small prostate and unresponsiveness to medical management, investigate other causes such as prostate infection (bacterial/viral), prostatitis, or pelvic floor dysfunction.
19. Urethral Carcinoma Workup for Small Prostate & Persistent Symptoms
If profound urinary symptoms persist with a small prostate and unresponsiveness to medical management, ensure a workup for urothelial carcinoma (cancer in the bladder/urethral lining) is performed, including urinary cytology.
20. Diagnostic Workup for Prostatic Infection (Stamey Test)
If concerned about a prostatic infection, undergo a four-step Stamey test (capture initial void urine, midstream urine, expressed prostatic secretion, and post-massage urine). Culture these samples, looking for bacteria at a lower threshold (10^2 or 10^3) than standard UTI diagnostics.
21. Consider Seminal Vesicle Infection for Pelvic Pain
In very unusual cases of persistent pelvic pain, consider a bacterial infection in the seminal vesicles. This can be diagnosed by bacterial testing of semen.
22. Myofascial Release for Pelvic Floor Tightness
If a rectal exam reveals tightness or ‘guitar string’ bands in the pelvic floor muscles, consider transrectal myofascial release therapy, as this can significantly alleviate pelvic pain syndrome.
23. Dietary Diary for Pelvic Discomfort
If experiencing pelvic discomfort or pain without clear cause, keep a thorough diary of food intake to identify potential dietary triggers, similar to interstitial cystitis in women.
24. Avoid Long-Term Antibiotics for Non-Bacterial Prostatitis
If experiencing chronic pelvic pain syndrome that improves with antibiotics but without confirmed bacterial infection, transition away from long-term antibiotic use. Instead, use NSAIDs (e.g., naproxen, ibuprofen, meloxicam) and potentially anxiolytics, as antibiotics often act as anti-inflammatories.
25. Explore Mast Cell Dysfunction for Chronic Pelvic Pain
For chronic pelvic pain syndrome with unknown etiology, explore mast cell dysfunction. Clinical trials are investigating mast cell inhibitors for this condition (e.g., at Northwestern Feinberg School of Medicine).
26. Good Hygiene & Catheter Management for Elderly
For elderly patients, especially those with dementia, maintain good hygiene and monitor voiding history to minimize the risk of urosepsis. If catheterization is necessary, intermittent catheterization is preferred over indwelling catheters due to lower infection risk, provided sterile technique is used.
27. Maintain Hydration in Elderly
For elderly individuals, especially those with comorbidities or dementia, ensure adequate hydration. Dehydration concentrates urine, increasing the risk of infection and urosepsis, as older people often lose their sensation of thirst.
28. Recheck Elevated PSA & Consider Advanced Testing
If an initial PSA test is elevated, always recheck it due to potential transient rises. Additionally, consider advanced PSA-based testing (e.g., percent-free PSA, prostate health index, 4K score) to increase specificity and discriminate between benign enlargement and cancer.
29. Interpret PSA Density
Understand PSA density (PSA value / prostate volume). A PSA density of 0.1 or less is generally safe for young men. For average age, if PSA density is more than 0.15, consider additional testing, as higher PSA density correlates with higher risk and aggressiveness of cancer.
30. Interpret PSA Velocity
Monitor PSA velocity (rate of PSA rise). A rapidly rising PSA is a canary in the coal mine, indicating a warning sign that requires additional evaluation.
31. Pre-Biopsy MRI for Elevated PSA
If you have an elevated PSA and are considering a prostate biopsy, always get a pre-biopsy multiparametric MRI (3T, T2, diffusion-weighted imaging, dynamic contrast enhancement if needed). This helps identify suspicious lesions (PI-RADS 3, 4, 5) and reduces unnecessary biopsies while enhancing detection of clinically significant disease.
32. Biopsy Suspicious MRI Lesions
If an MRI shows a suspicious lesion (PI-RADS 3, 4, or 5), consider a biopsy that samples both the specific lesion (target biopsy) and systematically samples the surrounding peripheral zone.
33. Transperineal Biopsy to Reduce Infection Risk
When undergoing a prostate biopsy, consider the transperineal approach over the transrectal approach, as it significantly reduces the risk of infection by avoiding the introduction of rectal bacteria into the prostate. This can often be done without antibiotics.
34. Buffered Lidocaine for Biopsy Pain Management
If undergoing a transperineal prostate biopsy, ask for buffered lidocaine for pudendal nerve blocks. Buffering the lidocaine (pH ~5) with bicarbonate reduces the burning sensation during injection, making the procedure more tolerable.
35. PSMA PET Scan for High-Grade Prostate Cancer Staging
If diagnosed with high-grade prostate cancer (Gleason 8+ or 4+3=7 with significant pattern 4), undergo a PSMA PET scan to determine the extent of the disease (staging). This is the most sensitive and specific way to identify metastases, as prostate tumors are not FDG-avid.
36. Active Surveillance for Low-Volume Gleason 6 Prostate Cancer
If diagnosed with low-volume Gleason 3+3=6 prostate cancer (least aggressive, 1-4 cores), active surveillance is generally recommended. This involves close monitoring (PSA every 6 months, confirmatory biopsy at 1 year, repeat MRI if PSA changes or initially missed) rather than immediate aggressive treatment, as the risk of progression to incurable disease is very low (0.1%).
37. Genomic Testing for Borderline Gleason 7 Prostate Cancer
For small-volume Gleason 7 (3+4) prostate cancer, especially with minimal pattern 4 (e.g., 1-2 millimeters), consider genomic testing (e.g., Decipher) to assess aggressiveness. Many such tumors behave like Gleason 6 and may be candidates for active surveillance.
38. Aggressive Treatment for High-Grade Prostate Cancer (Gleason 8+)
For Gleason 8 or higher prostate cancer (including 4+3=7 with significant pattern 4), aggressive treatment is typically required. These tumors have a higher probability of deep roots and spreading to lymph nodes, necessitating active intervention.
39. Multimodal Therapy for Aggressive Prostate Cancer
For high-grade prostate cancer (Gleason 8+ or 4+3=7 with significant pattern 4), especially with lymph node involvement, consider multimodal therapy (e.g., surgery followed by radiation, or radiation with androgen deprivation therapy) for aggressive treatment.
40. Inquire About Surgeon’s Specialization and Outcomes
When choosing a surgeon for prostatectomy, ask about their practice scope (e.g., prostatectomy-only vs. general urology), their surgical margin rates, and their rates of functional recovery (urinary continence, erectile function). Seek a surgeon with dedicated experience and transparent outcomes.
41. Pelvic Fascial Sparing Prostatectomy
When considering radical prostatectomy, inquire about pelvic fascial sparing techniques. This advanced surgical approach preserves surrounding fascia and structures, significantly improving urinary continence recovery and potentially erectile function without compromising cancer control.
42. Post-Prostatectomy Erectile Function Recovery
Understand that erectile function recovery post-prostatectomy is a long process (up to 24-30 months) and depends on age, pre-surgical function, and tumor aggressiveness. Be prepared for a 65-75% chance of recovery with Cialis for a healthy 65-year-old with contained cancer.
43. Penile Rehabilitation with Injectable Prostaglandins
Post-prostatectomy, consider using injectable prostaglandins (e.g., into the cavernosal body) as a temporary measure to trigger erections during the nerve recovery period. This helps reoxygenate the penis, maintain penile length, and support sexual activity.
44. MRI-Guided Radiation Therapy
If radiation therapy is chosen, inquire about MRI-guided prostate radiation. This advanced technique offers tremendous precision, real-time adjustments for patient movement, and the ability to boost specific lesions, significantly reducing rectal side effects and potentially improving cancer control.
45. Hydrogel Spacer for Radiation Toxicity Reduction
For radiation therapy, consider the use of a hydrogel spacer (SpaceOAR). This gel is percutaneously deposited between the prostate and rectum, separating them by 5-10mm, which substantially reduces radiation toxicity to the rectum.
46. Radiation Sensitization with Androgen Deprivation Therapy (ADT)
If undergoing radiation for high-grade or locally aggressive prostate cancer, androgen deprivation therapy (ADT) is often used as a radiation sensitizer. It induces double-strand DNA breaks, making cancer cells even more susceptible to the radiation.
47. Oral LHRH Antagonists for Short-Course ADT
For short-course ADT (e.g., 6-24 months) used with radiation, consider oral LHRH antagonists. These offer rapid onset and offset, increasing the likelihood of testosterone recovery compared to traditional LHRH agonists.
48. Systemic Therapy for Metastatic Prostate Cancer
For metastatic prostate cancer, systemic therapy is essential. This includes androgen deprivation therapy (ADT) with LHRH agonists/antagonists, often combined with novel hormonal therapies like CYP17 inhibitors (e.g., abiraterone) or androgen receptor competitive binders (e.g., enzalutamide, apalutamide, darolutamide) to significantly extend lifespan.
49. Testosterone Supplementation with Low T and Prostate Cancer
For patients with low testosterone and prostate cancer, especially luminal-type tumors, testosterone supplementation can be considered. Luminal tumors are exquisitely sensitive to testosterone suppression, and understanding tumor biology (e.g., via genomics) can guide this decision.
9 Key Quotes
If you increase your fluid intake, you're going to have increased urinary output. And so just basic educational things about that is really, really helpful.
Ted Schaefer
If your PSA begins to rise on finasteride, you have a problem. That is a warning sign that there is a cancer and likely an aggressive cancer growing in your prostate.
Ted Schaefer
It's not really, for the most part, what's in your DNA that matters. It's the epigenetic changes that result in the RNA translocation transition that really is the most important thing.
Ted Schaefer
The PSA is a remarkable test.
Peter Attia
If your PSA at age 40 or 50 is below the median, then your lifetime risk is very low.
Ted Schaefer
You order an MRI, which is frankly, like, surprising and appalling to me that I see second opinions in my office weekly that they never had any pre-diagnostic, i.e. pre-biopsy MRI. It's absurd to me.
Ted Schaefer
The chances that you would have a more aggressive cancer develop in the first five years of surveillance is 12.5%.
Ted Schaefer
The chances that a cancer progresses in surveillance to be uncurable? It's 0.1%.
Ted Schaefer
The higher the Gleason score, the higher the probability that that person can have deep roots in their tumor, extending outside the prostate, potentially into the periorectal fat and beyond.
Ted Schaefer
5 Protocols
Behavioral Modifications for Lower Urinary Tract Symptoms (LUTS)
Ted Schaefer- Regulate overall fluid intake to avoid excessive consumption.
- Time fluid intake, avoiding large volumes right before bed or after waking up at night.
- Identify and reduce intake of fluids with natural diuretic properties, such as caffeine and alcohol.
- Perform voiding diaries to track fluid intake and urinary output, helping to identify patterns and triggers.
Stamey Four-Glass Test for Prostatic Infection
Ted Schaefer- Capture the initial few cubic centimeters (cc) of urine (VB1) to sample bacteria in the urethra.
- After a few seconds, capture a midstream urine sample (VB2) to check for bladder infection.
- Pause urination, perform a vigorous rectal examination to express prostatic secretions (EPS), and attempt to capture this fluid.
- Immediately after the rectal exam, have the patient capture the beginning of the next urinary flow (VB3) to sample fluid from the prostate and urethra.
National Comprehensive Cancer Network (NCCN) Prostate Cancer Screening Guideline
Ted Schaefer (referencing NCCN guidelines)- Every man at age 45 should have a baseline PSA test to establish their individual baseline.
- If the PSA is below 1, recheck the PSA every two to four years.
Workup for Elevated PSA and Suspicion of Prostate Cancer
Ted Schaefer- Recheck the PSA to confirm elevation and rule out transient rises.
- Order advanced PSA-based testing, including percent-free PSA and potentially Prostate Health Index (PHI) or 4K score, to increase specificity.
- Perform a high-resolution 3T multi-parametric MRI of the prostate, including T2 images, diffusion-weighted imaging (DWI), and dynamic contrast enhancement (DCE), to identify suspicious lesions (PI-RADS scores 3, 4, or 5).
- If an MRI shows a suspicious lesion or if PSA density is high (e.g., >0.1 in young men, >0.15 in older men), perform a biopsy. This biopsy should target the suspicious lesion(s) and systematically sample other areas of the prostate.
Active Surveillance for Low-Volume, Low-Grade Prostate Cancer (Gleason 6)
Ted Schaefer- Conduct PSA testing every six months to monitor for changes.
- If the patient had not undergone an MRI before the initial biopsy, obtain an MRI immediately to assess for missed lesions or higher-grade disease.
- Perform a confirmatory biopsy at one year post-diagnosis to re-evaluate the tumor grade and volume.
- If PSA remains stable and no concerning changes are observed, continue monitoring with regular PSA tests and periodic MRIs.