The first slide summarized the landscape of currently available options for the treatment of advanced prostate cancer:
The first case is a 65-year-old man (EW) who is spiritually active (important as it affects his decision to get treatment), adopted (but has a twin brother who was also adopted with him), and has a pre-treatment PSA of 22. He has cT3N0M0 disease on conventional imaging. He is NOT interested in clinical trials. He declines surgery and ultimately chooses radiation therapy.
Audience question and response #1: What treatment would you have offered this high-risk advanced non-metastatic patient?
- ADT: 8%
- Radiation + Abiraterone: 10%
- Radiation + ADT: 74%
- Radiation + ADT + Docetaxel: 8%
Historically, ADT alone may have been a reasonable option – but in today’s world, the benefit of therapy to the primary is increasingly being recognized.
3-year post-treatment, EW has a BCR with PSA 5.7, PSADT > 12 months. Conventional imaging again negative. The patient decides to manage with prayer alone.
Audience question and response #2: What is your trigger to start ADT?
- Absolute PSA level: 9%
- PSA kinetics: 72%
- Disease evident with novel imaging: 11%
- No treatment until cM1 (CT/BS): 8%
This was mirrored by data from Partin et al., which also showed a wide range of metastases-free survival depending on Gleason grade, time to recurrence and PSA DT.3
PSA doubling times <6 months or <10 months are often used as markers of aggressive disease.
EW now presents again with a PSADT of 8 months and PSA 12.7. He is recommended to start ADT.
Audience question and response #3: What treatment would you offer now with a PSADT <10 months?
- ADT continuous: 41%
- ADT intermittent: 22%
- ADT+ Abiraterone: 32%
- No treatment until cM: 13%
EW is put on continuous ADT. He has a good response and has undetectable PSA for 12 months. Then PSA begins to rise (> 2.0). PSAST is now 10 months. Conventional imaging has no metastases. Continues ADT but declines other treatments – wants to rely on prayer alone.
Audience question and response #4: Do you agree that cM0 CRPC exists in 2019?
- Agree: 68%
- Disagree: 32%
A PSADT <6 months, in particular, is associated with an aggressive phenotype.
The panelists note that there are good therapies approved in this setting, and while you can look for radiographic evidence of metastases if it isn’t going to change management drastically, you have to weigh the benefits of these tests. As things are today, you have to look at his clinical picture – if he has slow progression and there is a role for local therapy, PSMA imaging may help. However, with aggressive disease, he probably warrants systemic therapy anyway.
At this time, they took a break from EW and focused on his brother, TW. TW had a radical prostatectomy at age 60, he is otherwise healthy. He underwent salvage XRT for detectable PSA post-operatively. He then was started on AST for BCR, but now has a rising PSA despite ADT. His PSADT is 6 months. Conventional imaging is negative. He meets ARAMIS/PROSPER/SPARTAN criteria. He has more money and is willing to pay out of pocket for any treatment, but not interested in trials.
Audience question and response #5: How would you treat this patient?
- Abiraterone + Prednisone: 12%
- Apalutamide: 45%
- Continue ADT alone: 4%
- Darolutamide: 20%
- Enzalutamide: 19%
The key take-home points are that the main outcome is now MFS, which has substituted OS and enabled earlier FDA approval. However, OS data is still immature. Dr. Davis does warn against potential lead-time bias with such studies. Dr. Rathkopf’s main point focused on the adverse event profile – you cannot compare these drugs head to head! Rather, you must compare them to their placebo arm. In all 3, they are all pretty well tolerated. Darolutamide, with its different structure, may not cross the blood-brain barrier – and therefore may account for the low “mental impairment” disorders side effect. However, apalutamide and enzalutamide may have more hypertension and fatigue compared to their placebo. Apalutamide, in particular, is associated with a higher rate of rash. These need to be considered independently and tailored to the patient.
TW gets one of the these “lutamides” and has a good response, with a PSA that drops to 0.5 and stays stable for 2.5 years. However, he then begins to have a rise at that time and his PSADT is now 8 months. Conventional imaging is again negative.
Audience question and response #6: Would you be likely to stop the “lutamide” drug?
- Most likely: 7%
- Fairly likely: 25%
- Likely: 21%
- Less Likely: 13%
- Not likely: 34%
TW gets a second opinion at an academic center. They obtain a PSMA PET CT and find 3 bone metastases/lesions. He is asymptomatic. He returns to your care.
Audience question and response #7: Should be now starting a new treatment since metastatic disease is now detected (on novel imaging)?
- Strongly agree: 26%
- Agree: 30%
- Neutral: 10%
- Disagree: 17%
- Strongly Disagree: 17%
However, in those patients, about 55% have distant metastases, 20% have regional disease and the remainder have local recurrence. So, if you get this novel imaging, expect it to be positive!
Audience question and response #8: What therapy would you recommend next in this asymptomatic patient with conventional imaging negative but novel imaging positive?
- Abiraterone + Prednisone: 19%
- Continue current therapy: 32%
- Docetaxel (or other chemo): 10%
- SABR: 33%
- Sipaleucel-T: 6%
Overall, this was a good session, with good audience participation.
Moderated by: Mark T. Fleming, MD, Chair, Virginia Oncology Associates, US Oncology Research, Virginia, USA
Panelists: Ian Davis, MBBS, Medical Oncologist, Monash University, Melbourne, Victoria, Australia; Dana Rathkopf, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, New York City, New York; and Fred Saad, MD FRCS, Urologist, Institut du cancer de Montréal, University of Montreal Hospital Research Centre, Montreal, Canada
Written by: Thenappan Chandrasekar, MD, Clinical Instructor, Thomas Jefferson University, @tchandra_uromd, @JEFFUrology at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA
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