#39 - Ted Schaeffer, M.D., Ph.D.: How to catch, treat, and survive prostate cancer
Dr. Ted Schaeffer, Professor and Chair of Urology at Northwestern, discusses prostate cancer screening (PSA, 4K, MRI), treatment, and controversies. He shares insights on surgical advancements, research, and advice for MD-PhD students, offering a comprehensive overview for men and their families.
Deep Dive Analysis
15 Topic Outline
Ted Schaeffer's Unique Path to an MD-PhD
Scientific Transition: Single Gene Focus to Complex Systems
Advice for MD-PhD Students and Choosing Urology
History of Prostate Surgery and Pat Walsh's Innovations
Prostatectomy Risks: Bleeding, Incontinence, and Sexual Function
Prostate Specific Antigen (PSA) Explained
PSA Screening Controversy and Impact on Metastatic Disease
Advanced Screening Tools: 4K Score, PHI, and MRI
Prostate Biopsy: Risks and Transperineal Approach
Gleason Grading System and Grade Groups
Testosterone, DHT, and Prostate Cancer Controversy
Prostate Metabolism and Exciting Research Areas
Benign Prostate Issues: Pelvic Pain and Infections
Advances in Surgical Technology: Robotic Prostatectomy
Male Contraceptive Options
8 Key Concepts
Tyrosine Kinases
These are proteins that modify other proteins within a cell by adding a phosphate group to a tyrosine residue, transmitting acute signals. They act as 'rheostats' to fine-tune cellular signals rather than just turning them on or off, and are attractive targets for cancer drugs like Gleevec.
Prostate Specific Antigen (PSA)
PSA is a protein produced by prostate epithelial cells, primarily functioning to liquefy semen. While prostate-specific, it is not cancer-specific; its levels in the blood can indicate prostate size, inflammation, or the presence of cancer due to leakage from the prostate into the bloodstream.
PSA Density
This metric helps urologists fine-tune PSA interpretation by dividing the PSA value by the prostate gland's volume. A higher PSA density can raise a red flag for prostate cancer risk, even if the absolute PSA number appears 'normal' for the patient's age.
4K Score / Prostate Health Index (PHI)
These are advanced blood tests that measure multiple prostate-specific proteins (PSA, free PSA, intact PSA, HK2 for 4K; minus two pro PSA for PHI). They are designed to better discriminate between benign prostate conditions and high-grade, aggressive prostate cancer, providing a percentile chance of having aggressive cancer.
Gleason Grading System
Developed by pathologist Donald Gleason, this system grades prostate cancer based on the architectural appearance of glandular abnormalities under a microscope. It assigns a primary and secondary pattern (1-5), which are summed to a Gleason score (e.g., 3+3=6), and has evolved into a 5-tier Grade Group system for clearer communication of aggressiveness.
Active Surveillance
A management strategy for low-grade prostate cancer (typically Grade Group 1, Gleason 3+3) where the tumor is monitored over time with regular PSA tests, rectal exams, and sometimes repeat biopsies or MRIs, instead of immediate active treatment like surgery or radiation.
Non-Myelinated Nerves
Nerves, such as those responsible for erectile function around the prostate, that lack a myelin sheath. This makes them incredibly sensitive to any manipulation or trauma during surgery, contributing to the difficulty in preserving sexual function post-prostatectomy.
Androgen Output of Tumors
This refers to how much a prostate cancer tumor relies on or produces androgens (like testosterone) for its growth. Counterintuitively, the most aggressive prostate tumors often exhibit the lowest androgen output, while high-output tumors are typically more sensitive to androgen deprivation therapy.
10 Questions Answered
PSA is a protein made by the prostate gland, and its normal function is to liquefy semen, which is important for sperm motility and egg fertilization.
PSA levels can rise due to aging (as the prostate enlarges and becomes 'leakier'), prostate infection (inflammation), or the presence of prostate cancer.
These tests measure multiple prostate-specific proteins to better differentiate between benign prostate conditions and high-grade, aggressive prostate cancer, providing a percentile chance of having aggressive cancer.
The Gleason system grades prostate cancer based on the architectural appearance of glandular abnormalities under a microscope, assigning a score (now a Grade Group 1-5) that indicates the tumor's aggressiveness.
Physiologic replacement of testosterone is not clearly linked to accelerating or causing prostate cancer to develop, and some data suggests the most aggressive tumors have low androgen output.
Historically, risks included extreme blood loss, urinary incontinence, and impotence. Modern techniques have significantly reduced these, but regaining full sexual function can still be challenging due to the sensitivity of non-myelinated nerves.
Almost all guidelines now recommend a shared decision-making process between the physician and patient, considering individual risk factors and preferences, rather than a universal screening mandate.
While some minor bleeding is common, the risk of a significant infection requiring hospital admission is low, with one institution reporting 0.4% in their series, though national data might show higher ER visit rates.
The most exciting research involves moving beyond prognostic biomarkers to predictive biomarkers, especially identifying DNA damage repair pathway mutations (like BRCA1/2) that predict sensitivity to specific drugs like PARP inhibitors.
Chronic pelvic pain syndrome is a broader term encompassing burning or pain in the urethra and bladder, which can include non-bacterial prostatitis (inflammation of the prostate without a bacterial infection).
16 Actionable Insights
1. Shared Prostate Cancer Screening
Discuss prostate cancer screening with your physician as a shared decision-making process, as there is no universal formal recommendation and stopping aggressive screening has led to a rise in advanced disease.
2. Utilize 4K Score/PHI Test
Consider using the 4K score or Prostate Health Index (PHI) test to assess the percentile chance of having high-grade, aggressive prostate cancer, as these tests help discriminate between cancerous and benign cells.
3. High-Quality Prostate MRI
If undergoing a prostate MRI, ensure it is a multi-parametric MRI with high-quality diffusion-weighted imaging (DWI) performed and interpreted by skilled professionals, as DWI is the most important parameter.
4. Prostate Biopsy Decision Algorithm
Follow an algorithm where a biopsy is recommended for abnormal MRIs or negative MRIs with high PSA density (>0.15), but may not be needed for negative MRIs with low PSA density, which can reduce unnecessary biopsies.
5. Genetic Testing for Metastatic PCa
If diagnosed with metastatic prostate cancer, consider genetic testing for DNA damage repair pathway mutations (e.g., BRCA1/2, ATM), as these mutations are enriched and may indicate sensitivity to PARP inhibitors.
6. Physiologic Testosterone Replacement & PCa
Physiologic testosterone replacement therapy is not clearly shown to accelerate or cause prostate cancer development, and aggressive tumors often have low androgen output.
7. Manage Non-Bacterial Prostatitis
If experiencing non-bacterial prostatitis (chronic pelvic pain syndrome), focus on managing symptoms and adjusting risk factors like constipation, as antibiotics may not be necessary for inflammation without infection.
8. Prostatic Massage for Inflammation
For non-bacterial prostatitis, a prostatic massage may help alleviate symptoms by reducing inflammation, potentially providing relief without antibiotics.
9. Targeted Antibiotics for Recurrent Infection
If experiencing recurrent bacterial prostate infections, discuss direct antibiotic injections into the prostate or seminal vesicles with your urologist, as these areas can harbor persistent bacteria.
10. MD-PhD Clinical Experience
MD-PhD students should do clinical time before their PhD to gain a practical understanding of important clinical questions and the human condition, which can inform their research.
11. Continuous Professional Learning
Establish a regular ‘adult only’ journal club with colleagues (medonks, radonks, urologists) to review new research articles in your field and related specialties, fostering continuous learning and staying current.
12. Only Order Actionable Medical Tests
Do not order a medical test unless you know what you will do with the results and how they will alter your management plan for the patient.
13. Explore New Opportunities
Never walk by an open door without looking inside; view new opportunities as exploration rather than risk to foster personal and professional growth.
14. Vasectomy and Sperm Banking
If considering a vasectomy, consider sperm banking beforehand, and ensure a skilled professional performs the procedure, as reversal rates are high with good technique.
15. Practice Safe Sex
Use protection (e.g., condoms) for safe sex, not just for contraception, especially if dating, to prevent sexually transmitted infections.
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5 Key Quotes
You never walk by an open door without looking inside.
Ted Schaeffer
You can't make important discoveries unless you work on important problems.
Pat Walsh
Don't order a test, don't do a test unless you know what you're, what you're going to do.
Peter Attia
The most aggressive tumors are the ones that have low androgen output.
Ted Schaeffer
The pursuit of excellence is something I think about all the time. And that was really the epitome of Hopkins for me.
Ted Schaeffer
1 Protocols
Prostate Cancer Screening and Biopsy Algorithm
Ted Schaeffer- Perform a PHI (Prostate Health Index) or 4K score blood test as an initial assessment.
- If the PHI or 4K score is abnormal, proceed to a multi-parametric prostate MRI, specifically focusing on diffusion-weighted imaging (DWI).
- If the MRI shows a suspicious lesion, perform a biopsy that samples the suspicious lesion and includes systematic biopsies (e.g., right, left, top, middle, bottom).
- If the MRI is negative (no lesion) but the PSA density is high (e.g., more than 0.15), a biopsy is still recommended.
- If the MRI is negative and the PSA density is low, no biopsy is needed.