In this four-part series of interviews with renowned medical oncologist Neeraj Agarwal, M.D., of the University of Utah’s Huntsman Cancer Institute, we have shown that ADT alone is not sufficient in treating early metastasis (metastatic hormone-sensitive prostate cancer, or mHSPC) – and that ADT works much better when it is combined with an androgen-receptor pathway inhibitor (ARPI; these drugs include enzalutamide, abiraterone, apalutamide, and darolutamide) or addition of docetaxel chemotherapy to the ADT plus ARPI combination. As we discussed, the results from several landmark studies over the last decade were so compelling that combination therapy is now the standard of care – even though many American men are not being offered this combined approach. We’ve talked about doctors’ misconceptions and discussed some of the financial roadblocks for patients.
So now here we are. “There’s no doubt that the treatment approach should be combination therapy,” says Agarwal. But there’s something he always tells his patients before they start: “Yes, you will feel overwhelmed, because your life has changed. But I have a lot of patients who are living for years – beyond a decade – and I give them this hope: You could be one of them.”
Just as the best way to target early metastasis is to hit it hard, right from the beginning, the best way to approach combination therapy is to address all of its potential side effects right up front. The drugs can take a toll, says Agarwal. “There’s fatigue, loss of muscle mass, the risk of metabolic syndrome, increased fat around the midsection, increased cardiovascular risk, increased risk of stroke, quality of life issues – hot flashes, inability to perform your daily duties to the max, and the effect of treatment on your marriage and romantic life. But there are ways to handle all of this.”
Here are some key points for clinicians and patients to consider:
Exercise: cardiovascular exercise with resistance training “is more important than ever.” Agarwal is principal investigator of an NCI-funded study that starts combination therapy patients on a yearlong exercise program. As PCF-funded investigators have shown, for men with mHSPC, any exercise is better than none, and even light weights and short bursts of exercise can make a big difference.
Taking care of the heart: “Screening for cardiac issues is more important than ever, too, says Agarwal. When he starts patients on ADT plus an ARPI, “it’s routine for me to do EKGs in my clinic, especially in those patients who seem to be prone to cardiac disease.” These include men who have a history of smoking, or who are overweight or who don’t have a very active lifestyle, or who feel short of breath. He works with cardiologists and family physicians to make sure the patients get a stress test, cholesterol and other blood tests, or other workups if needed.
Taking care of the bones: “So many times this is missed,” Agarwal says. “If somebody already has low bone density and then starts on ADT and an ARPI, he will start having fractures. Vitamin D, and calcium plus exercise really go a long way to help strengthen the bones. We recommend bone-modifying agents to those who have thin bones to start with.”
Social help can be huge: “It takes a village, especially in the early days,” says Agarwal. “I tell my patients, ‘You need to get over this immediate barrier, these seemingly insurmountable barriers of tests, medications, and insurance – so let’s work together.’ That’s why a social worker and financial counselor play such big roles in the beginning.”
And then… “These same patients, their insurance resolved, all the screening done, the combination therapy begun – their PSA has dropped. They are feeling great. They don’t have pain, they’re feeling much better. They come back and say ‘Thank you very much.’ After six months, their whole family has a sense of relief. Those first three to four months are crucial. And then, after six months, I really hope we can say we did it together.”
