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Few Unanswered Questions Remain for Nonmetastatic Prostate Cancer

Brandon Scalea
Published: Friday, Jan 11, 2019

Harsha Ranganath, MD

Harsha Ranganath, MD

The FDA approvals of 2 antiandrogen agents in 2018 have shifted the needle forward in the treatment of patients with nonmetastatic castration-resistant prostate cancer (CRPC), but a clear treatment sequence has yet to be established, said Harsha Ranganath, MD.

on Genitourinary Cancers, Ranganath discussed the current and future treatment of patients with nonmetastatic CRPC.

OncLive: What is important regarding treatment for patients with nonmetastatic CRPC?

Ranganath: It is important to keep the patient’s QoL and overall life expectancy in mind, because this is an area where patients are living longer and longer. There is value in prolonging disease- free survival, but you are doing that at the risk of potentially toxic drugs; this includes financial toxicity. If you are starting therapy on someone who is asymptomatic and nonmetastatic, you may be burning a bridge by introducing a therapy you cannot use later in the treatment course. For patients who are eligible for just surveillance, it all depends on their comorbidities and their overall goals of care. I have run into cases, for example, where there are drug interactions that you want to avoid.

What are the most notable drugs in this paradigm?

The agents I spoke about today are enzalutamide and apalutamide. In practice, we are starting many patients on one of these agents. In many cases, these patients are going on androgen therapy in the first-line setting anyway. These are drugs we are very familiar with and they are well tolerated. There is not much difference between these drugs in terms of profile. The most common AE is fatigue.

Do you want to use the most potent agent first?

All the agents we use, for the time being, are active in later lines of therapy. Again, these are typically patients who are not going to have rapid progression. These patients will live for years and will have access to these drugs in a later disease course.

What is the approach for those with bone metastases?

We have good data showing the efficacy of radium-223 dichloride in this patient population. Recent data presented at the 2018 ESMO Congress discussed the use of combination therapy with radium-223 and antiandrogen agents.


  1. Hussain M, Fizazi K, Saad F, et al. PROSPER: a phase 3, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) in men with nonmetastatic castration-resistant prostate cancer (M0 CRPC). J Clin Oncol. 2018;36(suppl 6S; abstr 3). doi: 10.1200/JCO.2018.36.6_suppl.3.
  2. Small EJ, Saad F, Chowdhury S et al. SPARTAN, a phase 3 double-blind, ran- domized study of apalutamide (APA) versus placebo (PBO) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC). J Clin Oncol. 2018;3(suppl 6s; abstr 161). doi: 10.1200/JCO.2018.36.6_suppl.161.

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