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Invited Commentary
August 5, 2021

Exploring the Causes of Death Among Patients With Metastatic Prostate Cancer—A Changing Landscape

Author Affiliations
  • 1Institute of Health Research, University of Exeter Medical School, Exeter, United Kingdom
JAMA Netw Open. 2021;4(8):e2120889. doi:10.1001/jamanetworkopen.2021.20889

Using data from the Surveillance, Epidemiology, and End Results program, Elmehrath and colleagues1 undertook a large retrospective cohort study of 26 168 patients with metastatic prostate cancer to determine the common causes of death in this population. Patients were followed up from the date of diagnosis to death or the end of the study period in 2016, and standardized mortality ratios were calculated (SMRs) for each cause of death. Most deaths occurred within 2 years of diagnosis (9869 of 16 732 deaths [59.0%]). Black patients had a higher risk of excess death overall compared with White patients (SMR, 6.68 [95% CI, 6.45-6.91] vs 5.66 [95% CI, 5.57-5.76]). Of all deaths in the cohort, 13 011 (77.8%) were due to prostate cancer, with 924 (5.5%) due to other cancers and 2797 (16.7%) due to noncancer causes. Cardiovascular disease (SMR, 1.34; 95% CI, 1.26-1.42), cerebrovascular disease (SMR, 1.31; 95% CI, 1.13-1.50), and chronic obstructive pulmonary disease (SMR, 1.19; 95% CI, 1.03-1.36) were the most common noncancer causes of death, and noncancer deaths were more common among older patients and patients with longer latency periods from diagnosis to death.

Recognizing the limitations inherent to SMR estimates, this study1 is important considering that most patients with prostate cancer survive their disease for several years after diagnosis. As such, identifying the causes of deaths among these patients may help with multidisciplinary treatment planning. Elmehrath et al1 postulate that hormone therapy treatments may increase the risk of cardiovascular and cerebrovascular disease in patients treated for metastatic prostate cancer, a theory that is supported by some epidemiological and biomedical evidence. Their finding of increased suicide rates among Asian or Pacific Islander patients and White patients with metastatic prostate cancer is a surprise and should be investigated further, considering that such deaths are potentially preventable.

Prostate cancer incidence in the US and other Western countries has increased significantly in recent decades, largely as a result of the widespread use of prostate-specific antigen (PSA) testing.2 However, the incidence rates in countries like the US are stabilizing2 following national recommendations to reduce PSA testing.3 Mortality from prostate cancer over the same period has decreased,4 which is thought to be associated with a combination of PSA testing detecting some cases of prostate cancer earlier, resulting in a lower incidence of metastatic disease at diagnosis, and greater availability of more-effective treatments for advanced disease.2 Systemic therapies for prostate cancer, such as hormone therapy and chemotherapy, are not without their adverse effects, including increased risk of cardiovascular disease and other cancers, as highlighted by Elmehrath and colleagues.1 This is particularly relevant for prostate cancer, which has a high long-term survival rate compared with almost all other cancer types,4 and signals the need for greater holistic care for patients receiving these treatments.

Prostate cancer is expected to remain the most common cancer diagnosed in male individuals in high-income countries in the next decade, with incidence in low-income and middle-income countries projected to increase much more rapidly in comparison.5 As observed in this study,1 most patients with metastatic prostate cancer die from it, rather than other possible causes of death, reinforcing the need for innovations to promote early-stage diagnosis. The recent development and implementation of new tests for prostate cancer detection may reduce the proportion of patients who receive a diagnosis at a late stage, although some metastatic disease at the time of diagnosis will likely still occur. Multiparametric magnetic resonance imaging (mpMRI) of the prostate before biopsy is one such test and has been shown to increase the detection of clinically significant prostate cancer compared with transrectal ultrasound–guided biopsy. mpMRI can also be used to guide prostate biopsy to reduce the risk of missed diagnoses that occur with transrectal ultrasound–guided biopsy biopsy.6 PSA testing is known to be falsely normal in some men with aggressive and/or metastatic disease,2 so the wider use of mpMRI may detect more clinically significant cancers earlier and help to reduce the burden of advanced prostate cancer in the future.

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Article Information

Published: August 5, 2021. doi:10.1001/jamanetworkopen.2021.20889

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Merriel SWD et al. JAMA Network Open.

Corresponding Author: Samuel W. D. Merriel, MSc, Institute of Health Research, University of Exeter Medical School, 1.18 College House, St Luke’s Campus, Heavitree Rd, Exeter EX1 2LU, United Kingdom (s.w.d.merriel@exeter.ac.uk).

Conflict of Interest Disclosures: Dr Merriel reported receiving grants from Cancer Research UK outside the submitted work. Dr Martins reported receiving grants from Cancer Research UK outside the submitted work. No other disclosures were reported.

Funding/Support: Drs Merriel and Bailey are supported by the Can Test Collaborative, which is funded by Cancer Research UK (C8640/A23385). Dr Martins is supported by a Cancer Research UK postdoctoral Fellowship (C56361/A26124).

Role of the Funder/Sponsor: The funders had no role in the analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Elmehrath  AO, Afifi  AM, Al-Husseini  MJ,  et al.  Causes of death among patients with metastatic prostate cancer in the US from 2000 to 2016.   JAMA Netw Open. 2021;4(8):e2119568. doi:10.1001/jamanetworkopen.2021.19568Google Scholar
Welch  HG, Albertsen  PC.  Reconsidering prostate cancer mortality: the future of PSA screening.   N Engl J Med. 2020;382(16):1557-1563. doi:10.1056/NEJMms1914228PubMedGoogle ScholarCrossref
Grossman  DC, Curry  SJ, Owens  DK,  et al; US Preventive Services Task Force.  Screening for prostate cancer: US Preventive Services Task Force recommendation statement.   JAMA. 2018;319(18):1901-1913. doi:10.1001/jama.2018.3710PubMedGoogle Scholar
Rawla  P.  Epidemiology of prostate cancer.   World J Oncol. 2019;10(2):63-89. doi:10.14740/wjon1191PubMedGoogle ScholarCrossref
Teoh  JYC, Hirai  HW, Ho  JMW, Chan  FCH, Tsoi  KKF, Ng  CF.  Global incidence of prostate cancer in developing and developed countries with changing age structures.   PLoS One. 2019;14(10):e0221775. doi:10.1371/journal.pone.0221775PubMedGoogle Scholar
Drost  FJ, Osses  DF, Nieboer  D,  et al.  Prostate MRI, with or without MRI-targeted biopsy, and systematic biopsy for detecting prostate cancer.   Cochrane Database Syst Rev. 2019;4(4):CD012663. doi:10.1016/S1569-9056(19)30534-2PubMedGoogle Scholar
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