Asympt pt on LHRH agonist for PSA-only recurrence dvlps isolated bone, LN mets. Tx?


Asympt pt on LHRH agonist for PSA-only recurrence dvlps isolated bone, LN mets. Tx?

An otherwise healthy 62-year-old asymptomatic man receiving an LHRH agonist for PSA-only recurrent prostate cancer (PSADT 12 months) develops an isolated bone and lymph node metastasis. What treatment would you likely recommend (with or without bone-targeted treatment)?

How would you care for the same patient if he were 80 years old?

 

Andrew J Armstrong, MD, ScM
Associate Professor of Medicine
and Surgery
Duke Cancer Institute
Duke University
Durham, North Carolina
Answer: 62 yo: Sip-T enz; 80 yo: Sip-T enz

For a 62-year-old asymptomatic man receiving an LHRH agonist for PSA-only recurrent prostate cancer who develops an isolated bone and lymph node metastasis, I would generally administer sipuleucel-T first. Since it takes only about a month to complete the cycle, I would probably follow up with enzalutamide.

I do not discriminate based on age. I look more at the patient’s comorbidities, their treatment goals and their preferences. If the patient were 80 years of age, I would treat in the same manner as the younger patient. In this situation, bicalutamide 50-mg dose would be a treatment alternative.

Johann S de Bono, MBChB, MSc, PhD
Professor of Experimental Cancer
Medicine and Honorary Consultant
in Medical Oncology
Head of Clinical Studies Division
of Drug Development Unit and of
the Prostate Cancer Targeted
Therapy Group
The Institute of Cancer Research
and Royal Marsden NHS
Foundation Trust
Sycamore House
Sutton, Surrey, United Kingdom
Answer: 62 yo: Enz or abi; 80 yo: Enz or abi

I would administer enzalutamide or abiraterone to a 62-year-old asymptomatic patient receiving an LHRH agonist for PSA-only recurrent prostate cancer who developed an isolated bone and lymph node metastasis, and I would not administer bone-targeted therapy. I would treat in the same manner if the patient were 80 years of age.

Prof Ronald de Wit, MD, PhD
Medical Oncologist
Erasmus MC Cancer Institute
Rotterdam, Netherlands 
Answer: 62 yo: Depends on original Gleason score; 80 yo: Depends on original Gleason score

Because the 62-year-old patient has early-stage disease and the PSA doubling time is more than 12 months, there is no urgency to initiate treatment if he is willing to wait for some time. I would need to have additional information about the initial Gleason’s score and how long he benefited from ADT. If the patient has a low Gleason score and has been responding to ADT for more than a year, I would consider abiraterone. For a patient with a Gleason score of 8 who has been responding to ADT for less than a year, I would begin treatment with docetaxel rather than abiraterone.

It’s typical for most patients to have rather indolent disease, and initiating treatment with abiraterone or enzalutamide and prednisone may cause some side effects. The decision to watch and wait or receive treatment depends on the patient. Some patients are terrified that their PSA level is increasing or that they have a new bone or lymph node metastasis, and they want treatment.

In the Netherlands, sipuleucel-T is not available, but this will be an option for patients in the United States. I would try to explain to the patient that there is no immediate need for systemic treatment and that I would prefer to reassess after 3 or 4 months and see what happens. Upon a new bone scan, if there are any changes other than a slight increase in PSA, I’ll see how the patient tolerates the idea of observation without therapy. If the patient asks for treatment, then I will be in favor of treating with abiraterone or docetaxel.

If the patient were 80 years of age, I would treat in a similar manner.

Leonard G Gomella, MD
The Bernard W Godwin Professor
of Prostate Cancer
Chairman, Department of Urology
Associate Director, Jefferson
Sidney Kimmel Cancer Center
Clinical Director, Jefferson Sidney
Kimmel Cancer Center Network
Editor-in-Chief
Canadian Journal of Urology
Philadelphia, Pennsylvania
Answer: 62 yo: Sip-T + abi or enz; 80 yo: Sip-T + abi or enz

Even though we don’t have a lot of good data on the use of sipuleucel-T in this setting, sipuleucel-T can be considered for this 62-year-old patient. The lymph node metastasis is a little bit of a concern, but with the data available to date I believe most physicians will go right to treating with an agent like abiraterone or enzalutamide, based on the new FDA approvals.

I would treat in a similar manner if the patient were 80 years old. The oral hormonal agents have proven themselves to be pretty benign when it comes to age. As opposed to chemotherapy, with which you can have some bone marrow reserve problems, I don’t think that is the observation with the hormone-related new agents for metastatic castrate-resistant prostate cancer.

Celestia S Higano, MD
Professor of Medicine and Urology
University of Washington
School of Medicine
Member, Fred Hutchinson Cancer
Research Center
Seattle Cancer Care Alliance
Seattle, Washington
Answer: 62 yo: Sip-T enz (on disease progression); 80 yo: Sip-T or enz

For this 62-year-old patient, I would administer sipuleucel-T and denosumab. If the PSA level continues to increase and the patient becomes symptomatic, I would probably add enzalutamide.

If this patient were a healthy 80 years old, I would probably do the same thing. But if he were an 80-year-old with a limited life expectancy, I probably wouldn’t administer sipuleucel-T. I would administer enzalutamide.

Philip Kantoff, MD
Chair, Executive Committee
for Clinical Research
Chief Clinical Research Officer
Chief, Division of Solid
Tumor Oncology
Vice Chair, Department of
Medical Oncology
Director, Lank Center for
Genitourinary Oncology
Dana-Farber Cancer Institute
Jerome and Nancy Kohlberg
Professor of Medicine
Harvard Medical School
Boston, Massachusetts
Answer: 62 yo: Nilutamide or sip-T abi (on disease progression); 80 yo: Nilutamide or sip-T abi

For this 62-year-old patient with metastatic castration-resistant prostate cancer with disease progression on an LHRH agonist, I would consider nilutamide or sipuleucel-T. My decision will depend on the tempo of the disease. If the disease were progressing rapidly, I would add bone-targeted therapy with either zoledronic acid or denosumab. Approximately two thirds of my patients are receiving denosumab and one third of them are receiving zoledronic acid. If the patient showed signs of disease progression, such as increasing PSA levels and disease progression on imaging, I would move on to abiraterone.

If the patient were 80 years old I would treat similarly, depending on the patient’s performance status, not age. My choice will be nilutamide or sipuleucel-T. I might be a little more cautious about using sipuleucel-T for the 80-year-old patient. Even though I have administered sipuleucel-T to patients who are 80 years old before, I’d be a little less likely to use it. I would go through the nilutamide step first and then move on to either sipuleucel-T or proceed to add abiraterone after that.

Eric A Klein, MD
Chairman, Glickman Urological
and Kidney Institute
Cleveland Clinic
Cleveland, Ohio
Answer: 62 yo: Sip-T abi or enz (on disease progression); 80 yo: Observation or sip-T abi or enz (on disease progression)

In the absence of a bone metastasis, I would go back and perform an extended pelvic lymph node dissection on this 62-year-old patient. There’s a neat study from Europe using C11-acetate as an imaging agent for patients post prostatectomy and post radiation therapy. That study showed a substantial disease-free survival and clinical progression-free survival in patients who had nodal metastases after primary therapy that were limited to the pelvis, if the surgeon goes back to remove it. However, if the nodal involvements are up in the retroperitoneum or elsewhere, then this approach does not help the patient.

Given the fact that he has an isolated bone metastasis, I might radiate that metastasis and then perform the pelvic lymph node dissection, if he were healthy and determined to have a long life expectancy. If he had a lot of comorbidities or his PSA level were more rapidly increasing, I would probably temporize a little more and see how quickly his disease progressed. One needs to get a sense of what the patient’s disease trajectory is. For the patient as is, with a long PSA doubling time, I would radiate his bone metastasis and take out his pelvic lymph node.

If surgical excision is not an option and the patient has a slow disease trajectory, I might consider sipuleucel-T. If his PSA level continues to increase and the patient becomes symptomatic, I would recommend either enzalutamide or abiraterone. Both agents are approved in this setting. My treatment approach will not change if the patient is 80 years of age unless he has a low life expectancy. If he were asymptomatic, with a long PSA doubling time, I would not treat any further but would use a watch and wait approach.

Daniel P Petrylak, MD
Professor of Medicine
Director, Prostate and
GU Medical Oncology
Co-Director
Signal Transduction Program
Yale Cancer Center
New Haven, Connecticut
Answer: 62 yo: Sip-T enz (on disease progression); 80 yo: Sip-T enz (on disease progression)

Whether the patient were 62 or 80 years old but asymptomatic and developed an isolated bone and lymph node metastasis while receiving an LHRH agonist, with a PSA doubling time of more than 12 months I would administer sipuleucel-T. If the patient’s PSA level increased and imaging indicated disease progression, I would start enzalutamide at that point.

A Oliver Sartor, MD
Medical Director
Tulane Cancer Center
Laborde Professor
of Cancer Research
Professor of Medicine
and Urology
Tulane Medical School
New Orleans, Louisiana
Answer: 62 yo: Sip-T enz (on disease progression); 80 yo: Sip-T enz (on disease progression)

For this 62-year-old patient, I would administer sipuleucel-T. If he starts to develop some clinical symptoms of disease progression, I would administer enzalutamide. With a PSA doubling time of more than 12 months, it means that this patient has a long time before the disease gets serious. For such a patient, sipuleucel-T would be an appropriate treatment in terms of disease burden and disease pace. This patient has low burden and a low pace and this is the best time to administer sipuleucel-T.

If the patient were an 80-year-old, I would treat similarly.

Neal D Shore, MD
Medical Director
Carolina Urology Research Center
Myrtle Beach, South Carolina
Answer: 62 yo: Sip-T abi or enz (on disease progression); 80 yo: Sip-T abi or enz (on disease progression)

This patient would be ideal for sipuleucel-T. If after a few months of receiving sipuleucel his PSA level increases and he becomes symptomatic, I would order a repeat scan to determine how many bony metastases there are. If there were new lesions, I would consider enzalutamide or abiraterone.

If the patient were 80 years old, I’d pretty much have a similar conversation with him, assuming his performance status was good at zero.