As we discussed in Part 1, the year 2015 was a milestone in treatment of early metastasis (metastatic hormone-sensitive prostate cancer, or mHSPC). For the first time, the CHAARTED study showed that men with mHSPC who began ADT plus chemotherapy (docetaxel) lived significantly longer than men who started treatment with ADT alone. This study was the first of several that changed the standard of treatment for mHSPC to combination therapy: ADT plus docetaxel or ADT plus an androgen-receptor pathway inhibitor (ARPI; these drugs include enzalutamide, abiraterone, apalutamide, and darolutamide) or ADT plus docetaxel plus an ARPI.
With combination therapy, median survival – again, some men live much longer – is now about five years, compared to around three years a decade ago, and the results continue to improve as new drugs are developed and doctors keep pushing the treatment envelope. This improvement is monumental, says medical oncologist Neeraj Agarwal, M.D., of the University of Utah’s Huntsman Cancer Institute – “particularly when you consider that some anticancer drugs get approved based on a three-month survival benefit. There is no doubt that ADT alone is not sufficient. It works so much better when it is combined with one of these ARPIs.”
And yet. This is not the case for thousands of American men with mHSPC, Agarwal continues: “A lot of patients in the U.S. – the richest country in the world – are not getting ADT plus ARPI or ADT plus ARPI plus docetaxel, up front. That is unacceptable in our view, because of the significant survival advantage and quality-of-life benefits associated with combination therapy.”
A “Pre-2015 Mindset”
What is the problem? Unfortunately, there are several.
“There is no shortage of evidence that combination therapy works,” says Agarwal. However, “the number one reason that combination therapy is not being used up front in patients with mHSPC is lack of awareness of the data.” A lot of clinicians , “including urologists and medical oncologists,” have a pre-2015 mindset about mHSPC. “They fear that if you use everything up front, what will you use later? They want to keep these therapies for the time when ADT fails.”
Agarwal is the senior author of a striking study published in 2023 in the Journal of Urology, looking at how physicians in different specialties treat men with mHSPC. “We found that combination therapy was underused as a first line of therapy across urology and oncology specialties despite evidence of improved survival,” he says. “In subsequent lines of therapy, ADT plus ARPI was prescribed more frequently across specialties,” but these men would have been better off if they had hit mHSPC with both barrels from the start.
“We found that many physicians are worried about the side effects of these medicines,” says Agarwal. “In a lot of medical oncology practices, doctors are dealing with many different types of cancer in a given clinic, so do they have enough time to delve into prostate cancer only? On the other side, many urologists are very busy surgeons. How much time do they have to spend on learning about the latest data? Misconceptions happen because of lack of awareness. They think, ‘these drugs have toxicities; we need to keep them for later.’ They’re not aware of the data; that’s why they have these misconceptions.”
High-Quality, Accessible Education
In a talk delivered at the 2023 annual meeting of the American Society of Clinical Oncology (ASCO), Agarwal recommended education – “not only of clinicians, but also of patients. There are very busy clinicians in small practices who don’t have six days to spend at ASCO or other large meetings. Big medical journals have a hefty subscription fee,” often costing hundreds of dollars each year. “For clinicians who don’t have access to those journals, or who don’t have time to go to the meetings, can we get the knowledge to them?” One way to do this is online, with free webinars – such as those as offered by PCF – and video conversations provided by its partner organizations, UroToday and ProstateCancerPatientVoices, available to both doctors and patients.
“We also need to reach patients,” Agarwal continues. “That’s why these PCF webinars are so important. Patients can learn about treatment and then ask their doctors, ‘Why don’t you prescribe combination therapy?’” Although “80 percent of patients say they rely on their doctor to determine their treatment, they also want to live as long as possible. They want to choose the treatment that will eliminate cancer completely, if possible. Very few patients are telling us they don’t want aggressive therapy.”
Agarwal would like to see current recommendations for mHSPC incorporated into the electronic medical record – “So when a physician chooses a diagnosis of mHSPC on the electronic medical record, ADT alone is not a treatment option. Then it will alert the doctor that this is not Level One evidence,” and point to combination therapy.
But it gets more complicated, as we will discuss in part 3: Roadblocks to Combination Therapy.
