RADICAL PC-2: Specialist Referral Improves Cholesterol Control but Not Cardiovascular Events in Prostate Cancer Patients
核心洞察
The RADICAL PC-2 trial enrolled 2,501 prostate cancer (搜索) patients across eight countries and found routine referral to a cardiologist or internist significantly improved cholesterol control and statin use.
Referred patients were more likely to receive statin therapy (63% vs. 40%) and blood pressure medication (56% vs. 49%), with significantly lower cholesterol levels over nearly six years of follow-up.
Despite these improvements, no significant difference emerged in cardiovascular death, heart attack, stroke, or heart failure between the referred and usual-care groups.
Men with prostate cancer (搜索) face a high risk of heart disease, particularly when treated with androgen-deprivation therapy (搜索) (ADT). A large, first-of-its-kind international randomized controlled trial led by Hamilton researchers found that routine referral to an internist or cardiologist improved cholesterol levels, but did not lead to fewer heart attacks, strokes, heart failure, or cardiovascular deaths.
The findings were simultaneously published in JAMA Internal Medicine and presented at the European Society of Cardiology (ESC) Congress on August 30, 2026, by Darryl Leong, the study's principal investigator and a senior scientist at the Population Health Research Institute (PHRI), a joint institute of Hamilton Health Sciences and McMaster University.
Trial Design and Patient Population
The RADICAL PC-2 trial enrolled 2,501 participants from eight countries — Canada, Brazil, Singapore, Colombia, India, Australia, Israel, and the United States — from 2015 to 2025. Participants were men with newly diagnosed prostate cancer (搜索) or those beginning ADT for the first time.
Participants were randomly assigned to one of two groups: the first received their usual cancer care, while the second received usual care plus referral to an internist or cardiologist. The specialist was asked to provide personalized advice on healthy eating and exercise, guidance on quitting smoking, a cholesterol-lowering medication (statin) regardless of existing cholesterol levels, and blood pressure medication if blood pressure was above target (130 mmHg).
Improved Risk Factor Management
After nearly six years of follow-up, participants referred to a cardiologist or internist were significantly more likely to receive statin therapy (63% versus 40%) and blood pressure medication (56% versus 49%) than those receiving usual care alone. Over time, the referred group also had significantly lower cholesterol levels.
Despite these improvements, there was no significant difference between the groups in cardiovascular death, heart attack, stroke, or heart failure during follow-up. Researchers noted that fewer participants experienced these complications than expected, making it harder to determine whether the referral strategy affected those outcomes.
"I was surprised that we didn't see a reduction in heart attacks, strokes, heart failure or cardiovascular death in the group referred to a specialist," said Leong, director of the McMaster University and HHS Cardio-Oncology Program, HHS cardiologist, and an associate professor with McMaster's Department of Medicine. "However, looking closely at the data, there is a signal suggesting a reduction in heart attacks, which is consistent with the cholesterol-lowering effect we observed. That finding needs to be confirmed through further research."
Identifying Who Benefits Most
An accompanying study published simultaneously in JACC: CardioOncology identified patients most likely to benefit from referral to a cardiovascular specialist. Men with blood pressure above 130/80, diabetes, or cholesterol above 4 mmol/L were found to be most likely to benefit.
In that stratified analysis, the treatment effect differed by baseline total cholesterol (≤4 mmol/L vs. >4 mmol/L) and by baseline blood pressure status (systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg vs. BP <130/80 mm Hg). The interaction for diabetes did not reach statistical significance, although the intervention effect estimates suggested a potential difference by diabetes status.
"The major findings from this stratified analysis of a large, pragmatic, international, randomized controlled trial of a structured cardiovascular intervention for patients with prostate cancer (搜索) are that more favorable intervention estimates were observed among participants with total cholesterol >4 mmol/L, self-reported hypertension or elevated baseline BP (systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg), and possibly diabetes," said Cristina Cano Garcia, MD, and Jehonathan Pinthus, MD, PhD, et al.
"This important international study works to establish an evidence base of who benefits and how they may benefit from cardiovascular and internist management of risk," said Bonnie Ky, MD, MSCE, FACC, editor-in-chief of JACC: CardioOncology.
Clinical Implications
Androgen deprivation therapy, a common prostate cancer (搜索) treatment, can increase the risk of diabetes, high blood pressure, and heart disease. While clinical guidelines recommend monitoring and managing these risks, there has been little evidence on whether adding cardiovascular care to prostate cancer treatment would improve outcomes for patients.
"When someone is diagnosed with prostate cancer (搜索), the focus is often on the cancer. But heart health is important too, especially for patients receiving hormone therapy," said Leong. "We wanted to understand whether involving a cardiovascular specialist could help patients manage risk factors like cholesterol, blood pressure and diabetes, follow healthier habits and lifestyle, and eventually improve their health."
Researchers say the findings highlight the importance of ensuring cardiovascular risk factors are addressed as part of routine prostate cancer (搜索) care. "Cardiovascular risk factors like high cholesterol, high blood pressure, diabetes and smoking are often poorly addressed in patients with prostate cancer," added Leong. "I hope these findings raise awareness of heart disease risk among both prostate cancer patients and their healthcare providers; and help doctors make smarter decisions about how we care for these patients so that conditions like high cholesterol, high blood pressure and diabetes don't get lost in the focus on cancer treatment."
Leong encourages prostate cancer (搜索) patients to ask questions about their heart health. "If you have prostate cancer, ask your healthcare provider what your blood pressure, cholesterol and blood sugar levels are, and whether they need to be better controlled. Taking care of your heart health is an important part of your cancer care."
This study was supported by the Movember Foundation/Prostate Cancer (搜索) Canada, Hamilton Health Sciences Research Strategic Initiative, the Canadian Cancer Society/Canadian Institutes of Health Research, Tolmar Pharmaceuticals, and PHRI.