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Rising PSA contributes to lack of clarity in nonmetastatic prostate cancer
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NEW YORK — PSA is an “imperfect biomarker” that should inform prostate cancer treatment but not dictate it, according to a presenter at HemOnc Today New York.
“It really is not everyone’s friend and, in some cases, it can be a nemesis in clinic,” Ravi A. Madan, MD, a prostate cancer expert from Bethesda, Maryland, said during his presentation. “It really requires education from you to the patient about how imperfect it really is.”
Rising PSA is scary for patients and — because of the plethora of treatment options available for prostate cancer —there is “almost a tantalizing desire” to switch too quickly from one treatment to another, Madan said.
“I think PSA often is a culprit in that drive,” Madan said. “It is so critical that we try to maximize the time each patient is on a therapy. Just because we have all of these agents doesn’t mean they are all going to work as effectively, and it doesn’t mean we should abandon therapies that are still biologically effective regardless of PSA.”
PSA contributes to a lack of clarity in several prostate cancer treatment settings.
In metastatic castration-resistant disease, PSA should not be the primary measure of treatment benefit. Rather, radiographic imaging, toxicity and patient symptoms should drive the process, Madan said.
Decision-making is more complicated in the nonmetastatic setting.
About 50,000 men each year develop nonmetastatic castration-sensitive disease, which means they have rising PSA after surgery or radiation therapy, have normal testosterone, and have conventional imaging — CT or bone scan — negative for disease.
“You know they have cancer but you don’t know where it is, and the treatment indications aren’t clear,” Madan said. “A lot of the focus on clinical development is in the metastatic area, and there is a lot of clinical trials in the oligometastatic area. But biochemical recurrence for nonmetastatic castration-sensitive disease is that area in between.”
Available treatment options include androgen deprivation therapy or surveillance.
“One thing we know from trials is that earlier ADT for these patients does not improve long-term survival,” Madan said. “There are retrospective data that show a quicker PSA doubling time suggests men are more likely to develop metastatic disease in 3 to 5 years.”
However, there are several unknowns, including the role for emerging PET technology for these patients and whether altering PSA doubling time in this population can delay metastasis.
There are several common strategies for this patient population. These include doing nothing, opting to wait until metastatic disease develops; treat based on PSA doubling time; start ADT at an arbitrary PSA number; start ADT based on anxiety of the patient, provider or both; undergo PET scan and act on it.
Ideally, clinicians should avoid the last three options, Madan said. Instead, he recommended treating based on PSA doubling time. Key steps include assessing patient anxiety and educating them about PSA doubling time data; monitoring until PSA doubling time falls within the range of 3 to 6 months; strongly encouraging ADT for men whose PSA doubling time is less than 3 months; and deploying ADT on an intermittent basis — two 3-month doses — and then following PSA and PSA doubling time.
There is no clinical role for PET imaging.
“I think clinical trials are a great option for these patients,” Madan said. “We need data to understand what these PET images are telling us.”
PSA also contributes to a lack of clarity for men with nonmetastatic castration-resistant prostate cancer, or M0 disease.
For these men, Madan recommended considering eligibility of previous trials in this setting, including PSA doubling time less than 10 months and a minimum PSA value (ie, 2).
He recommended assessing risk vs. benefit among elderly patients.
He emphasized it is unclear if enzalutamide (Xtandi; Astellas, Pfizer) or apalutamide (Erleada, Janssen) is the better treatment, and that there are cases when he may consider an older agent, such as bicalutamide.
In addition, it is unknown how PET imaging will impact these populations, Madan said. – by Mark Leiser
Reference:
Madan RA. Rising PSA: When to pull the trigger? Presented at: HemOnc Today New York; March 21-23, 2019; New York.
Disclosure: Madan reports his spouse has speakers’ bureau roles with Boehringer Ingelheim, Janssen and Pfizer.