Complexity in Managing Advanced Prostate Cancer

Daniel J. George, MD:What’s nice about the case that we’ve presented is that it’s pretty typical—a 65-year-old man presenting with intermediate-risk disease—and yet, this is a patient who has been treated by all 3 specialists. He has seen surgeons, and he underwent radical prostatectomy. He was referred to medical oncology, treated with abiraterone, and recommended for radium-223. He has seen a radiation oncologist and gotten radium-223. This patient has already benefited from multidisciplinary coordinated care, if you will.

In the future, he may benefit from other specialists, as well, and just because he has had a radical prostatectomy doesn’t mean there’s not a role for the urologist. There absolutely is. These patients are still at risk for urinary issues and can benefit from continued follow-up and care. In addition, this patient may need other forms of radiation. An external beam radiation can be given either during or after radium-223.

So, this is a great example of how we toggle from one therapy to another, how we involve different specialists, how we coordinate that care, and how we continue to work together to offer the patient everything we can to extend their survival.

The most important thing when it comes to multidisciplinary collaboration is communication. Pick up the phone and call somebody, and have clinic together so you overlap and can share patients. Have tumor boards where you’re discussing cases as a group. These are the things that bring us together as a field, and what’s really important is to recognize that we’re not fighting each other for cases. We’re not fighting each other for control. We’re fighting a cancer—that’s not the patient, that’s their cancer. The patient is part of this, and they’re part of our team. Communication with the patient, communication with each other—wise minds collectively, that collective experience—all of those things really go into optimizing care.

And I still benefit from the collaborations, the communication, and the tumor board discussion cases. The multidisciplinary clinic consists of Robert Lee, in radiation oncology in our group; Judd Moul, Mike Ferrandino, Tom Polascik, and other urologists in our group; Andy Armstrong in our group in medical oncology; Rajan Gupta in radiology; and with our pathologist Jiaoti Huang and others. This is our multidisciplinary team. We have palliative care folks, we have social workers, and we have nurses. This is a group effort. That shared communication back and forth is really what allows all of that to happen, and we continue to learn and improve our care together with each case that we share.

Prostate cancer today is already much more complex than just 5 or 6 years ago, when we had docetaxel chemotherapy for metastatic patients along with androgen deprivation therapy, and that was it. The only real question was when you were going to use chemotherapy or if you were going to use chemotherapy. That has changed now.

In just the last 5 or 6 years, now we have 6 treatment options to offer these patients, including second-line chemotherapy, radium, a couple of hormonal agents, sipuleucel-T, and bone antiresorptive agents. And there’s a whole new class of therapies coming that are going to be predicated on the biology of this disease—everything from DNA damage repair to neuroendocrine phenotypes and anaplastic disease and other drug targets involved in some of the genetics underlying the progression of this disease.

How we incorporate that is going to be critical. If we continue to function by treating patients with 1 drug at a time until that drug fails, we’re setting these patients up for failure. The way we’re going to go forward is by combining agents. We’re seeing this in some of the early clinical trials that were designed to do that. Some of the STAMPEDE trials and the CHAARTED trial demonstrated that chemotherapy with hormonal therapy really extended the survival on a much greater level than either of those therapies alone or in sequence.

I think we’re going to see the same thing when we start adding together other disparate mechanisms, including hormonal therapies with immunotherapy, with radiopharmaceuticals like radium, and with other targeted biologies as well. So, it’s going to be really critical that we start thinking differently in terms of both our drug development and even more importantly in our clinical practice. How we begin to incorporate drugs that were developed as monotherapies but now really belong in concert together is critical. I think radium-223/abiraterone is just 1 example. You can think of many others where patients could really benefit from the overlapping biology and the non-overlapping toxicities of these mechanisms.

Transcript edited for clarity.

December 2012

• A 65-year old gentleman presented to a urologist with urinary incontinence
• Digital rectal examination was unremarkable
• Serum prostate-specific antigen (PSA) level of 10.8 ng/mL
• Transrectal ultrasound and biopsy revealed adenocarcinoma of the prostate gland with Gleason score 7(3 + 4)
• Bone scan and CT showed no evidence of metastasis
• The patient opted for radical prostatectomy; pathology confirmed Gleason 7 prostate cancer with evidence of extracapsular extension and negative nodes; pT3aN0
• Immediately following surgery, his PSA level was undetectable (<0.1 ng/mL)

December 2014

• Two years later the patient developed disease progression
  • PSA level increased rapidly to 15 ng/mL
  • He was asymptomatic
• He was referred to an oncologist by his urologist
• Bone scan and CT were negative
• He was started on androgen deprivation therapy and had an initial response of PSA decline to 0.5 ng/mL

December 2015

• Over the next year, his PSA level increased to 35 ng/mL
• Repeat imaging studies were done:
  • Bone scan showed multiple boney metastases in the spine, pelvis, ribs, and femur
  • CT scan showed no visceral or nodal disease
• Within 3 months his PSA level rose to 145 ng/dL and he began complaining of fatigue and pain
• He was started on abiraterone and prednisone
• Additionally, he opted for therapy with radium-223
• After 3 infusions of radium-223 his PSA declined to <10 ng/dL; ALP remained stable
• After 6 cycles of treatment, CT and bone scan confirmed stable disease with no new metastases
• The combination was generally well tolerated; the patient experienced grade 2 anemia and fatigue