Navigating guidelines, parsing through the PSA, Survivorship, & More!
Become a pro when addressing prostate cancer! We tackle the nuances surrounding screening for this all-to-common cancer and discuss important considerations in survivorship with our guest Dr. Petar Bajic (Twitter: @PBajicMD, Instagram: @the.sexdoc) of Cleveland Clinic! You’re IN for a good time listening to this episode!
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● Producer,Writer, Show Notes, Infographic, Cover Art: Beth Garbitelli MD
● Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP, Beth Garbitelli MD
● Reviewer: Sai S Achi, MD MBA
● Showrunner: Matthew Watto MD, FACP; Paul Williams MD, FACP
● Technical Production: PodPaste
● Guest: Dr. Petar Bajic MD
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● Intro, disclaimer, guest bio
● Guest one-liner
● Case from Kashlak
● Epidemiology of Prostate Cancer
● Screening Basics
● What is the PSA?
● Next Steps After Elevated PSA
● Thresholds and techniques for biopsy
● Free PSA, Other testing modalities, Prostate MRI
● Active Surveillance Nuts and Bolts
● Take home points, Outro
Epidemiology of Prostate CancerProstate Cancer is one of the most common cancers in the United States (ACS 2022, Rawla 2019). The lifetime risk of a prostate cancer diagnosis is about 1 in 8 and the risk of dying from prostate cancer is about 1 in 41 (ACS 2022). However, the vast majority of these cancers are not life-threatening. Dr. Bajic usually tells his patients that they are more likely to die with prostate cancer than to die from it. Unfortunately, there is some emerging evidence that there might be a rising incidence of higher-grade disease and rates of metastasis at diagnosis have risen (Desai 2022, 2022 AUA Annual Meeting Presentation, Dr. Leo Borregales).
Screening for Prostate Cancer has evolved a lot over the past 30 years. The USPSTF recommends screening based on shared decision-making alone. However, per Dr. Bajic, many urologists approach screening more aggressively. The American Urological Association recommends shared decision making but endorses that the greatest benefit for screening is in men aged 55 to 70, of average risk (AUA 2018). Average risk means they do NOT have a strong family history of prostate cancer and not of African descent. Patients who do have increased risk for dangerous prostate cancers (Black men, strong family history) should be considered for PSA screening starting at age 40, with a shared decision making approach. It is not recommended to screen over the age of 70 (AUA 2018, USPSTF 2018). One of Dr. Bajic’s considerations is 10-year life expectancy, especially because the cancer is generally slow-growing.
Dr. Bajic recommends considering family history of cancer (including prostate cancer, BRCA-associated cancers) when determining importance of screening. His expert opinion is to consider age of relative affected, number of relatives affected, and the aggressiveness of the cancer (ie: it would be more concerning if a first-degree relative had prostate cancer, at a young age, and it was deadly.)
Just a note on the oft-quoted association of Black race with prostate cancer (ACS 2019): emerging research indicates that, like other health related outcomes linked with race, systemic racism, institutional barriers, inequitable care are driving factors that influence increased prostate cancer risk for Black men, not merely genetics (Lillard 2022). More studies are needed to understand any genetic link (ex: some data indicates West African men have much better outcomes than African American men (Odedina 2006).) When data is adjusted for access to care and standardized, guideline driven treatment, prostate cancer prognosis for black men is non-inferior (Dess 2019).
What is the PSA?
The Prostate Specific Antigen (PSA) is a component of ejaculate secreted by the prostate. One of its main functions is to make ejaculate less viscous to facilitate fertilization. PSA can be elevated in prostate cancer, benign prostatic hyperplasia, post-surgery/post-instrumentation, recent catheterization, or current UTI (Oesterling 1991). Ejaculation also elevates PSA (Rajaei 2013). Elevations can be transient (Eastham 2003).
First Steps After Elevated PSA
Unfortunately, screening for prostate cancer with PSA does not identify who will have significant cancers (Welch 2020). Biopsies that result from elevated PSA tests are also not without harms, as has been repeatedly documented in medical literature and is part of what drove the change in the USPSTF screening recommendations (Welch 2020, Penson 2015, Hoffman 2022). Up to 1-2% men have a hospitalization secondary to transrectal prostate biopsy (Evans 2017, JAMA podcast 2018).
Dr. Bajic recommends investigating a patient’s previous PSA levels, if available, to understand their baseline. Rapid rise in PSA is sometimes considered more concerning than gradual increase (D’Amico 2004, D’Amico 2005, Fang 2002 , but unfortunately, there is not a strong consensus on what rate constitutes a rapid rise and data has been mixed about its helpfulness in prognosis (Loughlin 2014, Vickers 2012, Bjurlin 2013). Dr. Bajic believes it is not unreasonable,if the level is abnormal but mid-range (ie: 4.5) to consider a repeat test in a month to assess if it is a transient increase. Given the impact of ejaculation on PSA, Dr. Bajic reports that some providers counsel patients to abstain from ejaculation for 24 hrs prior to PSA collection.
And what if PSA is super low?
The prostate is an androgen sensitive organ and can be impacted in hypogonadism, in fact PSA levels can be falsely low. When patients are treated for hypogonadism, they can see a rise in their PSA (Guay 2000, Rhoden 2005, ). There is a lot of emerging research in this area about if PSA can be used as a true biomarker for hypogonadism but Dr. Bajic reports that a very low PSA (ie: 0.1, 0.05 etc) certainly raises concerns for him of hypogonadism in that patient if they have never undergone prostate cancer treatment.
And a falsely low PSA does not rule out cancer if the patient has signs or symptoms concerning malignancy. Dr. Bajic reports that he performs digital rectal exams and has found non-PSA secreting prostate tumors that way.
Thresholds and Techniques for Biopsy
Dr. Bajic’s expert opinion is that any person with an elevated PSA should be evaluated by a urologist. There’s not a specific cutoff that’s universally agreed upon for biopsy. Per Dr. Bajic, some urologists use a cutoff of 4.0 ng/mL but many use age-related cutoffs. The most common method for biopsy is the transrectal approach, a quick, office-based procedure involving ultrasound probe placement in the rectum, local anesthetic administration, and sampling of 12 areas of the prostate where cancer is more likely. Most common risk from this is bleeding, transient worsening of lower urinary tract symptoms, but there is also risk of infection and sepsis (AUA 2018). . There are other approaches including, transperineal prostate biopsy which has a lower risk of infectious complications (Xiang 2019).
Free PSA and other testing modalities
The %Free PSA test can be used in patients who have an intermediate elevated PSA level between 4 and 10 ng/mL (Catalona 1998) Dr. Bajic reports the test is being used less frequently because it does not differentiate between low risk, low-grade prostate cancers that can be managed with active surveillance and those that are higher-grade prostate cancers (Huang 2018). A newer test that Dr. Bajic has access to but is not widely available is the ISO PSA which looks at isomer ratios and attempts to risk stratify patients based on that (Stovsky 2019).
Prostate MRI is also used to evaluate patients with elevated PSA. Radiologists use PI-RADS scoring to denote lesions. In Dr. Bajic’s practice, he uses MRI as a way to map the prostate and determine where he will biopsy. Dr. Bajic reports it is sometimes challenging to get a prostate MRI covered by insurance for patients who have elevated PSA but no prior prostate biopsy.
Nuts and Bolts of Active Surveillance
After biopsy, the tissue is examined. Malignant lesions are rated on the Gleason scoring system (Epstein 2014). The higher the Gleason score, the more aggressive-appearing the cancer will likely behave. Gleason scores above 8 should not be managed with active surveillance and instead are treated with traditional cancer treatment modalities of chemotherapy and radiation, per Dr. Bajic. Gleason score of 7 can have heterogeneous outcomes based on some nuances of the grade group (Kane 2017). However, below that range, (ie: below than or equal to Gleason score of 6) many cancers can be appropriately managed with active surveillance (Morash 2015). In Dr. Bajic’s practice he sometimes treats younger patients who have higher risk mutations but possibly an intermediate Gleason score more aggressively. Active surveillance involves active PSA monitoring. Dr. Bajic monitors every 3mo. He also utilizes Prostate MRI and repeat biopsies every few years to ensure that cancer is stable and not progressing.
Survivorship Tips and Pearls
Anyone who has been treated for prostate cancer should be having annual PSAs (and providers may consider every 6mo in the first five years) (Noonan 2016). PSA in a prostate cancer survivor who has undergone prostatectomy should be undetectable, per Dr. Bajic. Dr. Bajic notes that even if it comes back as normal because it is less than 4 ng/mL, if it is detectable at all then that is concerning for positive margins or a positive lymph node, in patients who have had their prostate removed. Either a subspecialist or PCP should be completing an annual digital rectal exam as well (Noonan 2016).
Kashlak Pearl: We should be screening our prostate cancer survivors for sexual and urinary side effects of treatment! No matter which prostate cancer treatment a patient had, they have similar side effects on sexual and urinary function (Noonan 2016). Even prostate radiation can have profound impacts on the pelvic floor and urogenital function per Dr. Bajic. Additionally, some post-treatment effects may occur years after initial treatment. Common concerns are erectile dysfunction and urinary incontinence (Noonan 2016). The erectile dysfunction in this population is driven by not just arterial insufficiency but neurogenic causes, which will not fully respond to traditional ED drugs such as sildenafil, per Dr. Bajic. Urology should be involved for patients with post-Prostate Cancer ED, as they often require more specialized treatments and procedures to improve sexual function.
Genital pain and pelvic pain are also common symptoms in patients after prostate cancer treatment, and pelvic physical therapy can be a helpful intervention for this, Dr. Bajic reports.
Patients who have received androgen deprivation therapy or hormone blockers may undergo symptoms of hypogonadism such as hot flashes, fatigue, loss of libido while they’re on the therapy although some patients report persistent changes. Some patients require lifelong suppression and will also have ongoing changes associated with hypogonadism. Dr. Bajic reports it is not unreasonable to check bone density and liver function in patients with ongoing hormone suppression (Noonan 2016).
Listeners will review guidelines for prostate cancer screening, determine best practices for PSA testing and patient counseling, develop understanding of limitations of PSA testing, recognize appropriate follow-up of prostate cancer screening, and understand basics of prostate cancer survivorship.
After listening to this episode listeners will…
1. Learn the prevalence and disease burden for prostate cancer in the United States.
2. Review the current evidence and guidelines for prostate cancer screening.
3. Recognize the limitations of prostate cancer screening in primary care and areas of
controversy in this topic.
4. Determine follow-up and interpretation of prostate cancer screening results.
5. Develop an approach to survivorship care of prostate cancer patients.
Dr. Bajic reports the following disclosures: Endo Pharmaceuticals: advisor (relationship has ended); Coloplast Corporation: consulting fee (relationship has ended). The Curbsiders report no relevant financial disclosures.
Garbitelli EC, Bajic P, Williams PN, Watto MF. “#371 Prostate Cancer: Screening, Advanced Testing, & Survivorship.” The Curbsiders Internal Medicine Podcast. http://thecurbsiders.com/episode-list December 12, 2022.
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screening considerations rest on statistical calculations of risk and benefit, harms from screening, etc. i would have liked more of this presented to flesh out the case for or against screening. eg it is often said that if you screen 1000 men for 10 you will save one life but lose at least one to unnecessary treatment and its complications. ergo a wash
Thank you so much for this great feedback and recommendations. We will definitely consider this for future episodes!
Hi folks, I'm an evidence-based medicine expert and I'm afraid this was a terrible podcast. The "expert" brought us back to the 1990's, dogmatically telling us to screen everyone with PSA, refer, and trust that the urologists will get it right. Where were the NNT's and NNTH's? Specialists are NOT experts on screening. Screening is the business of primary care. We are the specialists. Please do not have an expert with his biases lecture me to ignore the evidence of vast harm from PSA screening and little to no benefit (depending on the RCT). If you folks read this and listen, thanks!
I agree with Dr. Steinberg. Specialists' expertise is in the evaluation of a referral population, not screening decisions for the average-risk population, and it felt like this was a mismatch (between questions and guest expertise).
That is SO well stated Dr Steinberg. The episode wasn't entirely on screening but you are absolutely correct about primary care being the experts on cancer screening. One of the curbsiders said the AUA position is "to just do it" which isn't correct. They advise discussing harms and benefits/shared decision making. They should have mentioned that the AAFP does not recommend discussing it unless the patient inquires because it is a low value screening and we have more important topics to cover in our too brief patient encounters. And not only did he not discuss the NNTs or NNHs, he did not go into how to discuss harms and benefits. I don't consider a man informed unless he knows that there is no reduction in overall mortality; the reduction in PC specific mortality is 0-1.3/1000 in RCTs; the chance of avoiding metastases at diagnosis is reduced by 3/1000; the chance of a needing a biopsy at some point is 24% and the risk of sepsis from the biopsy is about 1 in 50; the chance of finding cancer-about 10% (before age 70) is way higher than it should be (overdiagnosis was not even touched on in the podcast); and the chance of ED and or incontinence is about 50/1000. In my practice "No thank you" is the usual result of shared decision making for PSA.
I agree 100% with Dr. Steinberg. I love the curbsiders and you guys are my go to source for keeping up with the latest for internal medicine! However, this episode and the a fib episode both are outliers for me - only the specialists’ view on a controversial topic that has decades of data to sift through and sort out. It would be great if you could get someone with a more balanced view who could really help us have a shared decision making conversation for both a fib (early rhythm control) and PSA screening. Thanks so much for all you do- you guys are amazing and very entertaining too!
We appreciate your feedback and will consider this for future episodes on prostate cancer and AFIB! Thanks so much for listening.