Case Clinic:
Elevated PSA
Munich Re’s medical experts respond to challenging underwriting scenarios
Healthcare professionals and management at a meeting
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    This series presents individual medical cases that feature challenging conditions, uncommon diseases, or an unusual presentation of symptoms. Below, we summarize a case, explain our research and analysis, and suggest an underwriting recommendation. Munich Re’s team of global medical directors continually track medical research so that primary insurers may benefit from evidence-informed risk assessments. It is our hope that analyses of more challenging cases will foster a greater awareness of medical progress and will help to expand insurability.

    Case: Elevated PSA

    The Munich Re medical team investigated the insurability of a 58-year-old male applicant with hypertension who, two years prior to application, was found to have an elevated PSA level of 4.7 ng/ml during a routine medical exam. He had no complaints, his blood pressure was controlled on Losartan, and there was no family history of prostate cancer. On digital rectal exam (DRE) the prostate was reported as symmetrically enlarged, otherwise normal. A repeat PSA eight months prior to application was higher at 5.6 ng/ml.

    The applicant was referred to a urologist for evaluation where he was noted to have LUTS (Lower Urinary Tract Symptoms) and an enlarged prostate on digital rectal exam (DRE) (estimated 50cc in volume) that was symmetric and without nodules or induration. A repeat PSA was 5.3 ng/ml and a Prostate Health Index (PHI) value was 32. A multiparametric MRI identified a PIRADS 2 lesion, prostate size of 61 ml, and no other abnormalities. On insurance labs, his PSA was 5.7 ng/ml and all other findings were considered normal. 

    Munich Re medical's response

    • Prostate specific antigen (PSA) is a glycoprotein that is expressed by prostate tissue. Because prostate cancer often disrupts the basement membrane and allows for greater excretion of PSA into the bloodstream, an elevated level is associated with an increased likelihood of prostate cancer. The association however is not strong, particularly at mild degrees of elevation, since there are a number of benign reasons for PSA to increase, the most common being the benign prostatic hypertrophy (BPH) that often accompanies aging.
    • Though there are no universally accepted “normal” values for PSA, and the likelihood of prostate cancer rises with increasing PSA levels throughout the range of values, PSA levels >4, or >3.5 in this age range, are often chosen as a point for additional assessment. 

    • Additional concerns are present if there is an abnormal DRE, if the PSA rose significantly from prior values, and/or if there is a strong family history of prostate cancer, especially at younger ages.   

    • It is important to keep in mind that prostate cancer is often a very indolent disease that does not even warrant treatment. The concern then is mostly for what is termed clinically significant prostate cancer (csPCa) that is more likely to have an aggressive disease course.

    • Other factors to better predict the likelihood of csPCa include PSA density, percent free PSA, PHI, 4K score, PCA3 and gene expression tests such as EPI and SelectMDx, though each of these has important limitations.   

    • Where available, multiparametric MRI is now becoming the standard of care for best assessing the likelihood of csPCa (and the indication for a prostate biopsy).

    • Mortality associated with an elevated PSA varies greatly based on these factors. Where the likelihood of csPCa is deemed to be low, even if low grade prostate cancer is present, the overall excess mortality risk is small. With greater csPCa concern, especially if there are suspicious MRI findings, the risk is much greater and a biopsy usually indicated. Even if the biopsy is then negative, there remains some added risk due to the limited sampling that occurs with prostate biopsies. 

    Final recommendation

    The Munich Re medical team recognized the potential of underlying prostate cancer due to the elevated PSA level. The increase in the PSA between visits is of uncertain concern as the PSA velocity of approximately 0.68/yr (5.6-4.7/1.33 yrs) is not particularly high but is certainly not favorable. The PHI result similarly was neither favorable nor within the high risk range. On a positive note, the subsequent MRI noting a PIRADS 2 lesion is associated with a low risk of csPCa, 5% or less.1-3 In addition, the PSA density of roughly 0.09 (PSA 5.3/61ml volume) is also favorable and supports the notion that the PSA elevations can be explained by BPH. 

    Given this favorable MRI finding and a favorable PSA density, and that there were no clearly adverse biomarkers or family history, the risk of important prostate cancer was deemed to be low and within a standard risk classification for mortality.  Morbidity risks can be accepted with an exclusion.

    The information provided herein is for general information purposes only and should not be relied upon as professional advice. Munich Re, and its employees, directors, officers, and representatives do not warrant, represent or guarantee the accuracy, completeness, or currency of any of the information provided herein and accept no liability whatsoever arising in any way from the use of or reliance on such information, including liability for direct, indirect, special, incidental or consequential damages.   © 2024 Munich American Reassurance Company. All rights reserved.

    References

    1. Remmers S, et al. "Reducing biopsies and magnetic resonance imaging scans during the diagnostic pathway of prostate cancer: applying the Rotterdam prostate cancer risk calculator to the PRECISION trial data." European Urology Open Science 36 (2022): 1-8. 2. Panebianco V, et al. "Negative multiparametric magnetic resonance imaging for prostate cancer: what's next?." European urology 74.1 (2018): 48-54. 3. Triquell M, et al. "Magnetic resonance imaging-based predictive models for clinically significant prostate cancer: a systematic review." Cancers 14.19 (2022): 4747.
    Contact the author
    Bradley Heltemes
    Dr. Bradley Heltemes
    Vice President & Medical Director of R&D
    Munich Re Life US
    Gina Guzman
    Dr. Gina Guzman
    Vice President & Chief Medical Director
    Munich Re Life US
    John F. White III
    Dr. John F. White III
    2nd VP & Medical Director
    Munich Re Life US
    Tim Meagher
    Dr. Tim Meagher
    Vice President & Medical Director
    Munich Re, Canada (Life)

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