Prostate Cancer Guideline Classifies Patients By Risk Status

FORT LAUDERDALE, Fla--The duration of anticipated survival aftera prostate cancer diagnosis, and therefore the period of timeat risk in the disease, is unique to prostate cancer in the influenceit exerts on selection of therapy.

If life expectancy is less than 5 years, in the asymptomatic patient,observation is "prudent, appropriate, and good therapy,"said Christopher Logothetis, MD, in his presentation of the preliminaryprostate cancer guideline developed for the National ComprehensiveCancer Network (NCCN).

The evidence that therapy can alter the course of prostate cancerin the first 5 years is very limited, and thus the goal in thesepatients is to avoid symptoms, "and that is defeated by earlytreatment of the asymptomatic patient," he said at the NCCN'sfirst annual conference.

On the contrary, if life expectancy is greater than 5 years, theclinician must try to divide patients into risk categories andselect appropriate therapy.

In the NCCN guideline, based on stage, Gleason score, and degreeof elevation of the PSA, patients are divided into low, intermediate,or high probability of having organ-confined disease, the predictorof adverse outcome after local therapy, said Dr. Logothetis, ofthe M.D. Anderson Cancer Center.

The Prostatectomy Paradox

The first questions for the prostate panel from the conferenceaudience related to the logic of choosing initial therapy. A physicianfrom Wisconsin asked for an explanation of the pros-tatectomyparadox: "If a patient has a high probability of organ-confineddisease and life expectancy less than 10 years, observation orradiotherapy is recommended and prostatectomy is considered apoor option. But if expected survival is longer, why does prostatectomythen become a good treatment?" he asked.

Dr. Logothetis responded that there are no data that prostatectomyin patients with a high probability of having organ-confined diseasealters the course of the disease, "and the toxicity dataseem to suggest that prostatectomy is more morbid than radiotherapyin most people's hands."

Based on those two pieces of information, the panel felt thatpatients with lower life expectancy could be treated with radiationtherapy or observation, he said, "but that a prostatectomy,whose only potential advantage over radiation therapy is a fractionallyhigher long-term cure rate, did not play a role in patients likelyto live less than 10 years."

For those patients likely to live more than 10 years, the advantagesof prostatec-tomy may be real, albeit unproven, he said, and thetwo treatments are on equal footing. He noted, however, that inthis situation, most physicians have a bias toward prostatectomy,"but that bias is not supported by the facts on survival."

Patients continue to die on their own despite the prostate cancer,he said, and the prostate cancer doesn't continue to progressin all patients. "When you look at the hard facts--not PSArelapses but survival data--there are no data showing that surgeryis superior to radiation therapy," he said, "even inthat subset with expected 10 year survival."

A Michigan physician asked what the panel would do when a radicalprostatec-tomy is performed and microscopic disease is found throughthe capsule or in the seminal vesicle, with negative nodes. "Isthere any role for radiotherapy after the resection?" heasked.

Dr. Logothetis called this question very controversial, sayingthat the panel ultimately felt that positive margins were notan absolute indication for radiation therapy. "If the PSAwas persistently elevated or subsequently rose, radiation therapycould be used if local presence of disease was documented,"he said.

Metastatic Disease

When asked if androgen ablation was the only option for patientswith M1 disease, Dr. Logothetis answered that "observationis an option in all the non-curable subsets of patients who areasymptomatic."

He also clarified the guideline recommendation regarding patientswith androgen-independent progression. "Although there isno established curative therapy for patients with androgen-independentdisease, there is a strong suggestion that these patients canbe palliated with chemotherapy." The guideline includes fivepossible chemotherapy combinations for use in this situation.

The prostate cancer guideline "is based on the assumptionthat you each can talk to your patients, describe the optionsthat are available to them in an honest way, and help them makea decision that suits their needs," Dr. Logothetis said.

He joked that "when you speak to a surgeon about therapyoptions, he'll describe a choice between radical retropubic orperitoneal prostatectomy. And if you talk to a radiotherapist,he'll say the options are external beam or brachytherapy. Obviously,there are many more options to be considered."

A medical oncologist in the audience said that he believes patientsare not being properly informed as to the potential value of radiotherapy,including a comparison of rates of impotence, incontinence, andmajor complications.

"Wouldn't it be helpful to suggest, early on in the guidelines,a multidiscipli-nary consultation, so that the medical oncologistsand radiotherapists also get an opportunity to educate a man makingthis difficult decision?" he asked.

Dr. Logothetis responded that this was addressed in the guidelineby the requirement for informed discussions with patients basedon the facts. "The very fact that we say that radiation therapyis equal to prostatectomy and put it in print and offer it topatients and publicize it, I think, puts a certain pressure oneverybody to have a valid discussion."

He went on to say that urologists are probably best at managinglocal symptoms and probably know the disease better than medicaloncologists "and, I suspect, better than radiotherapists.What we need to do is oblige the urologists to discuss the issueshonestly."

A physician from Boca Raton, Fla, a community with many retirees,indicated that urologists are routinely treating prostate cancermore aggressively than the guideline recommends.

"Some of the therapies that you denoted as experimental [eg,brachytherapy, cryotherapy] are being offered to patients as first-linetherapies," she said.

Dr. Logothetis commented that the guideline was designed to befiscally prudent and based on the existing data, "so we onlylooked at therapies with established effectiveness, either forpalliation, survival, or local control." But, he added, allof the NCCN guidelines expressly recognize that "enteringpatients into clinical trials is permitted and supported."

The Florida physician also qustioned whether elderly patientswill routinely accept observation. "If you tell someone whois 75 to 80 years old, 'we are just going to observe you becauseyour life expectancy may be less than 5 years,' they will shoparound for another opinion."

Dr. Logothetis disagreed somewhat, saying that "patientsare bright and want to make an informed decision." He believesthat physicians "routinely and effectively, talk to patientsand tell them: 'The reason we don't want to give you therapy isbecause we are optimistic that you are going to outlive this disease,and there is a good chance that by us intervening, we could shortenit.'"

Such patient education requires communication skills, honesty,and time, he said. "It takes more time to talk people intono therapy than it does to talk them into therapy, or even tomake them understand that no therapy is an option."

Dr. Logothetis reminded the audience that the prostate guideline,like the other NCCN guidelines presented at the meeting, "isa research effort, and continued assessment and modification areexpected." The challenge for the clinician, he said, is totake the guideline and, using his or her clinical experience andexpertise, apply it to individual patients.

NCCN Prostate Cancer Practice Guidelines Panel

Laurence H. Baker, DO, Chairman, University of Michigan ComprehensiveCancer Center

Gerald Hanks, MD, Fox Chase Cancer Ctr

Phillip Kantoff, MD, Dana-Farber Cancer Institute

Chris Logothetis, MD, M.D. Anderson Cancer Center

Howard Sandler, MD, University of Michigan Medical Center

Patrick Walsh, MD, The Johns Hopkins Hospital