Multidisciplinary Prostate Cancer Care at Duke Cancer Institute: An Interview With Judd W. Moul, MD

Judd W. Moul, MD

New clinical models are emerging for the delivery of prostate cancer care. Some large urology group practices are expanding to offer cancer care and instituting bone health clinics to treat patients throughout the entire course of their disease. In some academic settings, the concept of multidisciplinary prostate cancer care has been adopted, in line with a model that has become routine in breast and lung cancer assessment. In both the academic and group practice settings, new drugs are offering efficacy along with good tolerability, and the promise for a significant impact on patient care may be close at hand.

In a conversation with Urologists in Cancer Care, Judd W. Moul, MD, professor of Surgery and director of the Duke Prostate Center, Duke Cancer Institute, Durham, North Carolina, commented on practice trends in urologic cancer care and the advantages and disadvantages of his institution’s multidisciplinary prostate cancer clinic. He highlighted a few of the new treatments on the horizon for prostate cancer, and elaborated on the rationale behind the urology community’s disagreement with the recent US Preventive Services Task Force (USPSTF) recommendation against PSAbased prostate cancer screening.

Urologists in Cancer Care: Some urology practices, especially large groups, are expanding to provide cancer care, and establishing additional onsite services such as bone clinics. Could you reflect on this trend from an academic medical center perspective?Dr Moul: I think this offers a great opportunity for some of the large urology groups to find at least one partner or one member of the group who has a special interest in advanced prostate cancer. There are a number of new agents, either available now or in the pipeline. If urology groups do not embrace some of the new prostate cancer treatments, I am afraid they are going to lose out to medical oncology and some of the academic centers that are offering these services and treatments.

It has been said that the availability of more prostate cancer drugs with good tolerability and easy regimens such as oral administration also helps to make the case for urology practices to provide ongoing prostate cancer care.

I completely embrace urologists’ maintaining their role as the key physicians for men with prostate cancer—early and advanced. While I am enthusiastic about our continued role in pushing the technology envelope with early-stage prostate cancer, I am worried that many young urologists have focused so much on early-stage technology, such as the robot, and have not kept up or embraced the equally exciting new treatments for advanced prostate cancer.

Many LUGPA [Large Urology Group Practice Association] groups have adopted subspecialty expertise, such as having only one or two partners per group as robotic surgeons. In the same vein, I feel these groups need to embrace one or two partners as champions for new therapy for advanced disease—such as sipuleucel- T infusions, abiraterone use, or denosumab expertise. Urology remains a wonderful specialty because we can be surgeons and also be medical experts in our key diseases.

MDV3100 (enzalutamide) has been described as a “gamechanger” in the treatment of prostate cancer, having shown a significant survival benefit in men with prostate cancer post-docetaxel. Can you comment on these results and whether you agree with the claims about this oral drug’s potential?

MDV3100 has to be placed in the context of other products that have been FDA-approved in the last year or two years, such as sipuleucel-T, which is another treatment that large urology groups should embrace because of its low side-effect profile and evidence for increased survival in advanced prostate cancer. An advantage to MDV3100 is that it is an oral agent with a low sideeffect profile. It does not have to be administered with steroid medications and does not seem to have as many toxicities as some of the other oral agents that are currently being utilized.

You are an author of a recent paper that reports phase III results for zibotentan (ZD4054), an endothelin A receptor antagonist, in patients with castration-resistant prostate cancer [CRPC] that has metastasized to bone.¹ Can you comment on the results and the drug’s possible future in the expanding treatment armamentarium for CRPC?

This is a good news-bad news story. I was fortunate to be one of the global principal investigators on the trials for ZD4054, which was given the generic name of zibotentan by AstraZeneca, its developer. Unfortunately, those trials were all essentially negative and did not meet the endpoint of increasing survival in men with advanced prostate cancer. Currently the ZD4054 program has been discontinued, and the drug, at least currently, is not moving forward in advanced prostate cancer. I admire AstraZeneca for its commitment, with three global randomized studies, to determine if the drug would increase overall survival for advanced prostate cancer.

One of the ZD4054 trials was in men who had biochemical CRPC. These were men who had evidence of progression despite androgendeprivation therapy [ADT] but who still had a negative bone scan. When the patients were imaged for entry into the trial, fully one-third had bone metastases.² This finding teaches us that we need to reimage men to look for bone metastases when they have a rising PSA while on ADT. By detecting metastases, more men will be candidates for novel therapies including sipuleucel-T and denosumab.

Duke is one of a few medical centers with a multidisciplinary prostate cancer clinic, following from earlier examples of this type of service such as the one at Walter Reed Army Medical Center. You are among the authors of a recent report highlighting Duke’s utilization trends for its clinic over a five-year period.³ What would you cite as some of the advantages and disadvantages of the multidisciplinary clinic, and what did your study learn about utilization trends?

I am very fortunate to be at a medical center where we have embraced the concept of multidisciplinary care for advanced prostate cancer. We’ve had a multidisciplinary program since 2004. We are now celebrating our eighth year offering this service. We offer multidisciplinary care in two ways, including a “true” multidisciplinary clinic in which once per week, in one visit, patients will see a urologist, a medical oncologist, and radiation oncologist. After we all have seen the patient, we meet as a group to discuss the patient’s case in a kind of tumor board setting, then go back to the patient and give him our recommendations and options for treatment. Typically we see about a half-dozen patients in a five-hour morning session/clinic where all three specialists see and interact with the patients. Each takes a history and conducts a physical.

The patients and their families love this. The down side it that it takes three specialists much time out of their weekly practice, and I am not sure that it is a financially rewarding exercise. But certainly it is a great thing to offer and tremendous value-added service. And it may pay dividends in word-of-mouth recommendations, bringing a lot more patients to the center.

We also offer a pseudo-multidisciplinary option, where doctors are in their individual clinics but our new-patient coordinator lines up patients to see all three specialists the same day: urology, radiation oncology, and, in some cases, medical oncology.

Figure. Baseline Characteristics of Patients Who Received Care at Duke's Multidisciplinary Clinic Versus the Duke Urology Clinic

Variable

Multi-D Clinic

Urology Clinic

P

Age (yrs)

60 (IQR 53-65)

60 (IQR 55-64)

0.821

Black

26 (13.5%)

111 (16.8%)

0.272

BMI (kg/m²)

27.9 (IQR 25.2-30.6)

27.9 (IQR 25.2-30.5)

0.580

D'Amico

High Risk

44 (22.8%)

84 (12.7%)

0.003

BMI indicates body mass index; IQR, interquantile range.

Stewart SB, Banez LL, Robertson CN, et al. Utilization trends at a multidisciplinary prostate cancer clinic: initial 5-year experience from the Duke Prostate Center. J Urol. 2012;187:103-108.

The utilization trends from our true multidisciplinary prostate cancer clinic were published in the Journal of Urology last January.³ We looked at the first approximately 700 patients who went through the true multidisciplinary clinic between the years 2004 to 2011, comparing utilization determinants with the urology prostate cancer clinic (Figure). We identified the factors that were associated with pursuing treatment at the university medical center for multidisciplinary clinic patients. We found that about 60% of men who attended the multidisciplinary clinic ended up getting their primary treatment at Duke. For these Duke-treated men, about 52% went on to radical prostatectomy, 33% had primary radiation, and 9% elected active surveillance. High-risk men (PSA > 20, or Gleason score 8-10, or clinical stage T2c-T3) were more likely to decide on staying at Duke for their initial treatment. For the 40% of men who came to Duke for the multidisciplinary clinic but who did not stay at Duke for primary therapy, those living more than 100 miles from Duke, and those with higher socioeconomic status were less likely to be retained for care

Does the clinic setting—either or both the multidisciplinary and the pseudo-multidisciplinary—result in recruitment of more patients into clinical trials?

The clinic has increased the clinical trial participation rate because we have more time to speak to the patients about trials. Since patients are so happy otherwise because they got such good education, they appear to be more inclined to participate in clinical trials, perhaps as a result this “high-touch environment.”

We are involved in a large number of trials in local and advanced prostate cancer, and are trying to do a better job of informing our patients about clinical trial opportunities and trying to incorporate clinical trials into our practices on a daily basis. Some of the large urology group practices have done a great job with clinical trials. Dr Neil Shore and his partners in Myrtle Beach, South Carolina, immediately come to mind. They have embraced the concept of clinical trials embedded into a large community urology private practice and generally are better positioned to attract many trials compared to major academic centers. While we in academics do a great job as well, we sometimes take too long to approve trials and are more expensive due to our complex structure.

You and your colleagues have published several recent articles on chemoprevention with finasteride—cost-effectiveness, age at start of therapy, duration of therapy, quality of life.^4,5 Could you speak to this issue and to the findings?

Prostate cancer chemoprevention with finasteride or dutasteride remains extremely controversial. On the one hand, these drugs have some tremendous benefits: they will shrink the prostate. They will improve a patient’s symptoms (lower urinary tract symptoms), and they typically will cut the PSA level by about one-half. They also have the benefit of being approved to treat benign prostatic hyperplasia [BPH]. Finasteride is generic as well, so it is not expensive. For the patient with BPH, and in our practices, the drugs have made a huge impact. Those are the good things.

The challenge is that some experts, including the FDA, feel that the drugs might slightly increase the rate of high-grade cancers. So, the FDA was thumbs down on dutasteride for a pure chemoprevention indication, noting a slight chance of increasing the risk of high-grade cancer. Right now, neither finasteride nor dutasteride is approved for chemoprevention. On the other hand, urologists commonly prescribe these drugs for BPH. I personally think that the benefit may outweigh the risk for chemoprevention. There are also other data to suggest that the drugs might delay prostate cancer progression in men who are on active surveillance for low-grade, low-stage prostate cancer as well.

What new data from the American Urological Association [AUA] or American Society of Clinical Oncology [ASCO] this year were especially exciting and potentially meaningful to the urology community in the treatment of prostate cancer?

One of the things I thought was really a bombshell revelation at ASCO in June was reported by Maha Hussain, MD, an investigator with the Southwest Oncology Group [SWOG], who presented long-term follow-up results on the intermittent versus continuous hormone therapy trial.⁶ In patients with traditional metastatic prostate cancer, intermittent hormone therapy was inferior to continuous hormone therapy. That was quite interesting and probably something that many urologists may not be aware of.

The practical implications of this are significant. For patients with traditional advanced prostate cancer who are initiated on hormone therapy, the new standard may return to continuous androgen-deprivation therapy, away from intermittent hormone therapy. This suggests that some of the more potent hormone therapies such as degarelix or abiraterone or enzalutamide may make sense. For a while we were wondering what it all means, that if intermittent was just as good as continuous hormone therapy, then what is the big deal about keeping the testosterone level low? With this new intermittent data, at least for traditional advanced prostate cancer patients with bone metastasis, continuous hormone therapy appears to be better, and perhaps some of the newer agents that keep the testosterone levels really low may be better.

Significant controversy has erupted over the recent US Preventive Services Task Force [USPSTF] recommendation against PSA testing. A number of professional groups representing urologists, such as the AUA, men’s health groups, and LUGPA, have issued strong statements of disagreement—even rejection—of the USPSTF recommendation. What are your and your colleagues’ views on the issue of PSA testing for asymptomatic men, and how might it affect your clinical decision-making?

I was very fortunate to be part of a group of authors that published a rebuttal to the US Preventive Services Task Force. My views were put in writing in the Annals of Internal Medicine in May 2012.⁷

I think the biggest reason that urologists are frustrated is the fact that the USPSTF really did not recognize PSA as having any value in any man. They did not take into account some newer data suggesting that a baseline PSA level at age 40 is a powerful tool to stratify men for future risk of prostate cancer. They didn’t take into consideration African-American men, whom we know to be at much higher risk for prostate cancer. And they did not take into account men who have a strong family history of prostate cancer. They made a blanket statement that PSA should not be used in anyone.

While I agree that PSA is probably overutilized in elderly men, I disagree in that they threw the baby out with the bath water, and did not recognize PSA to be of value in high-risk groups nor its role in risk stratification. With a D recommendation, the Medicare program will not pay for PSA screening. We can code for diagnostic PSA or to follow patients. In North Carolina, if a Medicare patient comes in and if I code for “screening PSA,” patients must pay $205 out of pocket.

References

1. Nelson JB, Fizazi K, Miller K, et al. Phase 3, randomized, placebo-controlled study of zibotentan (ZD4054) in patients with castrate-resistant prostate cancer metastatic to bone [published online ahead of print July 11, 2012]. Cancer. doi:10.1002/cncr.27674.
2. Yu EY, Miller K, Nelson J, et al. Detection of previously unidentified metastatic disease as a leading cause of screening failure in a phase III trial of zibotentan versus placebo in patients with nonmetastatic, castration resistant prostate cancer [published online ahead of print May 12, 2012]. J Urol. 2012;188(1):103-109.
3. Stewart SB, Banez LL, Robertson CN, et al. Utilization trends at a multidisciplinary prostate cancer clinic: initial 5-year experience from the Duke Prostate Center. J Urol. 2012;187:103-108.
4. Stewart SB, Scales CD, Moul JW, Reed, SD. Does variation in either age at start of therapy or duration of therapy make chemoprevention with finasteride cost-effective? [published online ahead of print July 10, 2012]. Prostate Cancer Prostatic Dis. doi:10.1038/pcan.2012.26.
5. Reed SD, Scales CD, Stewart SB et al. Effects of family history and genetic polymorphism on the cost-effectiveness of chemoprevention with finasteride for prostate cancer. J Urol. 2011;185:841-847.
6. Hussain M, Tangen CM, Higano CS, et al. Intermittent versus continuous androgen deprivation in hormone sensitive metastatic prostate cancer patients: results of S9346 (INT-0162), an international phase III trial. J Clin Oncol. 2012;30(suppl; abstr 4).
7. Catalano WJ, D’Amico AV, Fitzgibbons WF, et al. What the U.S. Preventive Services Task Force missed in its prostate cancer screening recommendation. Ann Intern Med. 2012;157(2):137-138.