Old Saying About Prostate Cancer Not True When It's Metastatic

Nick Mulcahy

September 02, 2021

October 25, 2021 // Editor's note: The opening paragraph of this story has been changed for clarity.

Nearly 80% of men who died in a large cohort of metastatic prostate cancer patients died from their malignancy, according to a retrospective study involving 26,000-plus American men diagnosed with advanced disease in roughly the last 20 years.

The findings fill an information gap because, remarkably, "data are lacking" on causes of death among men whose prostate cancer has spread to other sites, say lead author Ahmed Elmehrath, MD, of Cairo University, Cairo, Egypt, and colleagues.

"It was an important realization by our team that prostate cancer was the cause of death in 78% of patients," said senior author Omar Alhalabi, MD, of University of Texas MD Anderson Cancer Center, Houston, in an email to Medscape Medical News.

"Most patients with metastatic prostate cancer die from it, rather than other possible causes of death," confirm Samuel Merriel, MSc, Tanimola Martins, PhD, and Sarah Bailey, PhD, University of Exeter Medical School, Exeter, United Kingdom, in an accompanying accompanying editorial. The study was published last month in JAMA Network Open.

The findings represent the near opposite of a commonly held — and comforting — belief about early-stage disease: "You die with prostate cancer, not from it."

That old saying is articulated in various ways, such as this from the Prostate Cancer Foundation: "We can confirm that there are those prostate cancers a man may die with and not of, while others are very aggressive." The American Cancer Society says this: "Prostate cancer can be a serious disease, but most men diagnosed with prostate cancer do not die from it."

However, these commonplace comments do not cover metastatic disease, which is what the authors of the new study decided to focus on.  

The team used data from the Surveillance, Epidemiology, and End Results Program (SEER) database to gather a sample of 26,168 US men who received a diagnosis of metastatic prostate cancer from January 2000 to December 2016. They then analyzed the data in 2020 and found that 16,732  men (64%) had died during the follow-up period.

The majority of these deaths (77.8%) were from prostate cancer, 5.5% were from other cancers, and 16.7% were from noncancer causes, including cardiovascular diseases, chronic obstructive pulmonary disease, and cerebrovascular diseases.

Senior author Alhalabi acknowledged a limitation in these findings — that the SEER database relies on causes of death extracted from death certificates. "Death certificates have limited granularity in terms of the details they can contain about the cause of death and also have reporting bias," he said.

Most of the prostate cancer deaths (59%) occurred within 2 years. The 5-year overall survival rate in the study group was 26%.

The deadliness of metastatic disease "reinforces the need for innovations to promote early-stage diagnosis," comment the editorialists. Striking a hopeful note, they also say that "new tests for prostate cancer detection may reduce the proportion of patients who receive a diagnosis at a late stage."

Death From Other Causes

The mean age at metastatic prostate cancer diagnosis in the study was roughly 71 years. Most of the cohort was White (74.5%) and had a diagnosis of stage M1b metastatic prostate cancer (72.7%), which means the cancer had spread to the bones.

Among men in the cohort, the rates of death from septicemia, suicide, accidents, COPD, and cerebrovascular diseases were significantly increased compared with the general US male population, the team observes.

Thus, the study authors were concerned with not only with death from metastatic prostate cancer, but death from other causes.

That concern is rooted in the established fact that there is now improved survival among patients with prostate cancer in the US, including among men with advanced disease. "Patients tend to live long enough after a prostate cancer diagnosis for non–cancer-related comorbidities to be associated with their overall survival," they write.

The editorialists agree: prostate cancer "has a high long-term survival rate compared with almost all other cancer types and signals the need for greater holistic care for patients."

As noted above, cardiovascular diseases were the most common cause of non-prostate cancer-related deaths in the new study.

As in the management of other cancers, there is concern among clinicians and researchers about the cardiotoxic effects of prostate cancer treatments.

The study authors point to a 2017 analysis that showed that men with prostate cancer and no prior cardiac disease had greater risk of heart failure after taking androgen deprivation therapy (ADT), a common treatment used when the disease recurs after definitive treatment. Another study suggested an association between cardiotoxic effects of ADT and myocardial infarction regardless of medical history in general.

The authors of the current study say that such findings highlight "the importance of multidisciplinary care for such patients and the role of primary care physicians in optimizing cardiovascular risk prevention and providing early referrals to cardiologists."

Further, the team says that tailoring "ADT to each patient's needs may be associated with improved survival, especially for patients with factors associated with cardiovascular disease."

Who should lead the way in multidisciplinary care? "The answer probably is case-by-case," said Alhalabi, adding that it might depend on the presence of underlying morbidities such as cardiovascular disease and COPD.

"It is also important for the oncologist ('the gatekeeper') to try to mitigate the potential metabolic effects of hormonal deprivation therapy such as weight gain, decreased muscle mass, hyperlipidemia, etc," he added.

The study had no specific funding. The study authors and editorialists have disclosed no relevant financial relationships.

JAMA Netw Open. Published online August 5, 2021. Full text, Editorial 

Nick Mulcahy is an award-winning senior journalist for Medscape, focusing on oncology, and can be reached at  nmulcahy@medscape.net  and on Twitter:  @MulcahyNick

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