expert roundtables

Metastatic Consequences of Prostate Cancer: Initial Treatment

by Peter R. Carroll, MD, MPH, E. David Crawford, MD, Leonard Gomella, MD, and Neal D. Shore, MD, FACS

Overview

Expert panelists describe initially seeking the most tolerable therapy that is appropriate for the phenotype of the patient’s disease, based upon the patient’s symptoms and the rapidity of disease progression. The experts also discuss the significance of symptomatic disease and of the source of the symptomology. Given the multiple approved therapies for metastatic castration-resistant prostate cancer (mCRPC), each with its own attributes and differing windows of opportunity for use, the panelists note the importance of planning ahead, and of timely action, so as not to miss an opportunity for therapeutic layering that could translate to longer survival and improvements in quality of life.

Q:

When patients recur with metastatic disease shortly after treatment, how does this factor into your treatment decision?

Peter R. Carroll, MD, MPH

Ken and Donna Derr – Chevron Distinguished Professor
Taube Family Distinguished Professor in Urology
Department of Urology
UCSF - Helen Diller Comprehensive Cancer Center
University of California, San Francisco
San Francisco, CA

Patients who have high-risk disease to begin with (as defined by cancer grade, prostate-specific antigen [PSA], and tumor volume) are more likely to relapse, and to relapse earlier. They are generally characterized by earlier relapse and usually unfavorable PSA kinetics. The patients who have lower-risk disease who relapse late with favorable kinetics are the ones who either have locoregional recurrence or have tumors that may be metastatic or with favorable biology. This is where positron emission tomography (PET) imaging is identifying these patients. These could be patients who underwent initial therapy. You image them, and you find that they may have a solitary lymph node occurrence. We’ve seen supraclavicular metastases as well as mediastinal metastases – isolated relapses. It’s really defining how we manage these patients. As mentioned earlier, many patients who would have undergone systemic therapy alone are getting a more targeted approach with surgery or stereotactic body radiation (SBRT).

Q:

What are some of the clinical factors that help guide the selection of therapy initially for patients with M1 CRPC?

Neal D. Shore, MD, FACS

Medical Director and CPI Carolina Urologic Research Center Managing Partner, Atlantic Urology Clinics
Myrtle Beach, SC

Most patients, when they develop metastatic disease – if they have been followed pretty closely during the transition from androgen sensitive to castration resistant – are going to be asymptomatic. If they have documentation of radiographic disease and they are asymptomatic and M1 CRPC, I am happy to discuss with them the options of sipuleucel-T, and/or starting a novel oral hormonal therapy, either abiraterone acetate or enzalutamide.

We’ve generated some phase 2 data demonstrating very nicely that one can combine sipuleucel-T with either abiraterone acetate or with enzalutamide. But usually, because sipuleucel-T is given over such a short period of time (4-6 weeks), it’s not really a challenge or a concern to start concomitant therapy. If the patient finishes the sipuleucel-T and then is started on a novel oral hormonal therapy [eg, he has bone-predominant disease, and maybe with some small, soft tissue disease but no visceral disease (which is a very common presentation)], I’ll start him on an oral therapy after we review the advantages and disadvantages of the 2 agents. Patients can have very long response duration, in the range of 12 and 24 months, or sometimes it is much shorter.

If while on treatment the PSA starts to rise and the patient is not necessarily showing any radiographic progression of disease and no change in symptomatology, I will maintain that therapy, and I rarely will make a switch – unless I am looking at a clinical trial. I also inform my patients that the use of all of these therapies is something that I want them to consider receiving over their cancer care journey. If there are new lesions and/or any change in symptomatology, then I will be very quick to switch to or add another therapy. I am not a proponent of switching from abiraterone to enzalutamide or enzalutamide to abiraterone, unless it’s part of a clinical study. In a real-world practice, I’d much rather consider radium-223, if, indeed, the patient is having some new symptomatology related to his bone disease, and there’s a good window of opportunity in my judgment to complete the recommended 5-6 cycles of radium-223.

 

“I am not a proponent of switching from abiraterone to enzalutamide or enzalutamide to abiraterone, unless it’s part of a clinical study. In a real-world practice, I’d much rather consider radium-223, if, indeed, the patient is having some new symptomatology related to his bone disease.”

Neal D. Shore, MD, FACS

I generally start with an agent that I believe will be the most tolerable therapy that is appropriate for the phenotype of the patient’s disease, based upon his symptoms and the rapidity of his disease progression, radiographically and/or with serologic parameters such as PSA, hemoglobin, lactate dehydrogenase, and alkaline phosphatase. I have a conversation with the patient, frequently explaining that, at some point, I will certainly be offering him and most likely will have very good benefit from taxane-based chemotherapy, which will include either docetaxel or cabazitaxel.

Q:

Dr Gomella, do you have any thoughts on the layering of agents or choosing initial therapy for patients with symptomatic metastases?

Leonard Gomella, MD

Chairman, Department of Urology
Bernard W. Godwin, Jr. Professor of Prostate Cancer
Sidney Kimmel Medical College
Sidney Kimmel Cancer Center
Thomas Jefferson University
Philadelphia, PA

Once patients present with symptoms due to advanced prostate cancer, all currently approved first-line mCRPC agents can be used, except for sipuleucel-T. There is a spectrum of how patients present, however, and in the modern world, patients are not really presenting as often with the prominent symptomatic disease they might have had in the past. That’s because, hopefully, if men have been treated for local disease and then they develop metastatic disease, and then they proceed to a castrate-resistant space, they’re being followed fairly closely. Their symptom evolution may not present as it might have decades ago, when patients would present more often with spinal cord compression or pathologic hip fractures. So, I think that, beyond minimal disease, with sipuleucel-T being one of those agents that you might want to think about first, everything else after that – unless you are really severely symptomatic – really comes down to whether the inclination is to use abiraterone or enzalutamide or radium-223 or docetaxel or other agents. It’s really up to the individual clinician and his or her comfort level, in conjunction with the patient and individual characteristics of the patient.

“Once patients present with symptoms due to advanced prostate cancer, all currently approved first-line mCRPC agents can be used, except for sipuleucel-T.”

Leonard Gomella, MD

E. David Crawford, MD

Professor of Urology
University of California, San Diego
Former, Distinguished Endowed Professor of Surgery, Urology, and Radiation Oncology
Head, Section of Urologic Oncology
University of Colorado Anschutz Medical Campus
Aurora, CO

We published a paper recently in Urology on the consensus from RADAR II, where we looked at therapeutic layering, examining some of the principles involved in layering on newer agents. We’ve got new drugs that are all different. The idea of putting them together is challenging, but it’s also exciting.

“We’ve got new drugs that are all different. The idea of putting them together is challenging, but it’s also exciting.”

E. David Crawford, MD

References

Crawford ED, Petrylak DP, Shore N, et al. The role of therapeutic layering in optimizing treatment for patients with castration-resistant prostate cancer (prostate cancer radiographic assessments for detection of advanced recurrence II) [RADAR II]. Urology. 2017;104:150-159.

Oudard S, Fizazi K, Sengeløv L, Sartor O, et al. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: a randomized phase III trial-FIRSTANA. J Clin Oncol. 2017:JCO2016721068.

Small EJ, Lance RS, Gardner TA, Shore N, et al. A randomized phase II trial of sipuleucel-T with concurrent versus sequential abiraterone acetate plus prednisone in metastatic castration-resistant prostate cancer. Clin Cancer Res. 2015;21(17):3862-3869.

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