Ep 158: A 58-Year-Old with an Elevated PSA

This episode talks about prostate-specific antigen (PSA) screening.

Read more on this topic in Harrison's.

Harrison's Principles of Internal Medicine, 22nd Edition

Transcript

[upbeat intro music] 

[Ms. Heidhausen] This is Katerina Heidhausen, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest content from the best minds in medicine. And now, on to the episode. 

[music continues] 

[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy. 

[Dr. Wiener] And I'm Dr. Charlie Weiner, and we're joining you from the Johns Hopkins School of Medicine. Welcome to today's episode, which is a 58-year-old with an elevated PSA. Cathy, we're back in your clinic like we were a few weeks ago. 

[Dr. Handy] Putting pressure on me. 

[Dr. Wiener] Okay, well, today's patient is a 58-year-old man with a past medical history only notable for mild hypercholesterolemia, which is well controlled with atorvastatin. His primary care physician checked the PSA at his last routine physical, and it was elevated at 2.2 nanogram per milliliter. His primary care physician reports his physical examination, including a digital rectal examination, as entirely normal. The patient's now coming to ask you, what's next? 

[Dr. Handy] Well, let's start with some background. The American Cancer Society estimates are that in the US, there are going to be over 300,000 new prostate cancer cases and about 35,000 deaths from prostate cancer this year. 

[Dr. Wiener] That is death from cancer, not with cancer, right? 

[Dr. Handy] Key point: the absolute number of prostate cancer deaths has decreased in the past 10 years. However, the paradox of management is that although 1 in 8 men will eventually be diagnosed with prostate cancer and the disease remains the second leading cause of cancer deaths in men, only 1 in 41 men with prostate cancer will die of this disease. The decision to pursue a diagnosis of prostate cancer must balance the benefit from detecting and treating clinically significant cancers that left untreated would adversely affect a patient's quality and duration of life. And you compare that against the morbidity associated with the overdiagnosis and overtreatment of clinically insignificant cancers that are highly prevalent in the general population. 

[Dr. Wiener] Yeah, and that's why screening is still a bit controversial, right? 

[Dr. Handy] It's why shared decision-making is so important. 

[Dr. Wiener] Which takes us back to our patient. One of the reasons why he's concerned about this abnormal PSA result is because his brother, who's 65 years old, has been told that he has prostate cancer and is already being followed for the disease. 

[Dr. Handy] That's important to know. Epidemiologic studies show that the risk of being diagnosed with prostate cancer increases 2.5-fold if one first-degree relative is affected and 5-fold if two or more are affected. Current estimates are that 40% of early onset and 5-10% of all prostate cancers are hereditary. Prostate cancer affects ethnic groups differently. So matched for age, African American males have a higher incidence and present at a more advanced stage with higher grade, more aggressive cancers. There are a growing number of gene associations, and newer risk scores are being developed to take into account more of the genetic ancestry. So this field is evolving quickly. What's the question asking? 

[Dr. Wiener] So the question is asking, which of the following statements regarding prostate cancer screening and prevention is true? Option A. most men with a PSA greater than 2 nanograms per milliliter will develop lethal prostate cancer. Option B. prostate biopsy is not recommended for this patient at this time. Option C. men with a PSA below 4 nanograms per milliliter have no risk of prostate cancer. Option D. patients with an elevated PSA should always receive a course of antibiotics before any additional workup. Option E. radical prostatectomy would be recommended for this patient, given his elevated PSA and his family history. 

[Dr. Handy] Okay, let's start with some background on PSA since that's why he's here today, and three of the options deal with it. PSA or prostate-specific antigen is a serine protease that causes liquefaction of seminal fluid. It's produced by both non-malignant and malignant epithelial cells, and as such as prostate-specific, but not prostate cancer-specific. Serum levels of PSA may increase from other causes besides prostate cancer, and that would be things like prostatitis and benign prostatic hypertrophy. 

[Dr. Wiener] Okay, let's talk about levels, in particular, in reference to prostate cancer screening. 

[Dr. Handy] PSA testing was approved by the US Food and Drug Administration in 1994 for the early detection of prostate cancer. Information from the Prostate Cancer Prevention Trial demonstrates that there's no PSA below which the risk of prostate cancer is zero. So PSA level establishes the likelihood that a man will harbor cancer if he undergoes a prostate biopsy. The goal is to increase the sensitivity of the test for younger men, harboring clinically significant cancers that may cause symptoms and shorten survival, and to reduce the frequency of detecting cancers of low malignant potential in elderly men more likely to die of other causes. 

[Dr. Wiener] Okay, so that rules out option C. Men with a PSA below 4 do have a risk of prostate cancer. This man's PSA level is 2.2. Where does that level put him? 

[Dr. Handy] Most prostate cancer deaths occur among men with PSA levels in the top quartile, over 2 nanograms per milliliter. Although only a minority of men with a PSA over 2 will develop lethal prostate cancer. 

[Dr. Wiener] Okay. So that rules out option A. Tell me about the other options. 

[Dr. Handy] Option D. mentions treating an elevated PSA with antibiotics. It is true that bacterial prostatitis will elevate PSA, and patients with symptomatic bacterial prostatitis should have a course of antibiotics before any biopsy looking for cancer. However, the routine use of antibiotics in an asymptomatic man with an elevated PSA level is discouraged. 

[Dr. Wiener] Should he undergo a biopsy or a radical prostatectomy without any biopsy? 

[Dr. Handy] He should not have either. Definitely, he should not have a radical prostatectomy. Radical prostatectomy is one of the treatment options for early-stage disease, and that's along with radiation or watchful waiting and active surveillance being the other option, but he doesn't have a diagnosis of prostate cancer yet. And PSA alone is not diagnostic in this setting so you would not move right to surgery. 

[Dr. Wiener] Okay. Well, that leaves us with option B. being true. You're not going to recommend he get a biopsy? 

[Dr. Handy] Not at this time with just this information. Given his age, I do think he should be followed with annual PSAs, and PSA over or at least 4 nanograms per milliliter is a commonly used cutpoint for prostate biopsy. Again, shared decision-making is important. So when a biopsy is pursued, we're moving away from blind biopsies only to ultrasound or MRI-targeted biopsies to really improve the diagnostic yield and characterize high versus low-risk tumors. So imaging is typically the next step, even before a biopsy. 

[Dr. Wiener] Great. We really should think about visiting prostate cancer therapy in the future, but the teaching points from today's case are that prostate cancer is very common among older men, and most men die with the cancer and not from the cancer. PSA is specific to the prostate, but is not specific for prostate cancer. PSA screening can be used to help the patient and the physician with shared decision-making, balancing the risk of lethal disease versus false positives or low-grade indolent disease. 

[Dr. Handy] And you can find this question and other questions like it on Harrison's Self-Review. And to read more, you can check out the Harrison's chapter on prostate cancer. Visit the show notes for links to helpful resources, including related chapters and review questions from Harrison's, available exclusively on AccessMedicine. If you enjoyed this episode, please leave us a review, so we can reach more listeners just like you. Thanks so much for listening. 

[upbeat outro music]