Physicians Take Aim at Localized Prostate Cancer Treatment Controversy in 'Shootout'

CHICAGO--Until recently, physicians would have offered watchfulwaiting only to a select group of older men with localized prostatecancer. Now, because of concerns about the quality as well asthe length of life, physicians are vigorously debating whetherwatchful waiting may be an option for men as young as the early50s.

"Surveillance should be offered to all patients who are newlydiagnosed with prostate cancer because the data do not providea compelling argument that there is a lower age at which surveillanceis not acceptable," argued Ian M. Thompson, Jr., MD, at theChicago Prostate Cancer Shootout, a debate over the treatmentfor localized prostate cancer sponsored by the Chicago RadiologicalSociety, Chicago Urological Society, and Chicago Medical Society.

Dr. Thompson, chief of the Urological Service, Brooke Army MedicalCenter, Fort Sam Houston, Texas, reported that he recently hadextended the watchful waiting option to a 52-year-old man witha small tumor and a prostate-specific antigen (PSA) value of 4.2ng/mL because surveillance is the only form of treatment thatcarries no side effects.

Even in the best of hands, Dr. Thompson pointed out, radical prostatectomyresults in impotence in at least 30% of patients. Among men whoare capable of erections before radical prostatectomy, only about40% can achieve erection afterwards, and only 12% can accomplishpenetration. At least one study indicated that 63% of men hada problem with incontinence after surgery, which may have affectedtheir quality of life.

Glenn S. Gerber, MD, assistant professor of surgery and urology,University of Chicago Medical School, acknowledged that disease-and metastasis-free survival at 10 years is similar regardlessof the method of treatment for men with grade 1 prostate cancer.

The data suggest that most men with mild or moderately differentiatedcancer will survive 10 years if left untreated, and that overallsurvival or life expectancy of 10 years or less will not improvewith surgery or radiation, Dr. Gerber said.

However, the same study showed that after 10 years, more than40% of patients exhibited bone metastases. "While it is certainlytrue that patients who are placed on watchful waiting will avoidthe side effects of radical prostatectomy and radiotherapy, theymay suffer tremendous morbidity because of metastatic disease,"Dr. Gerber stated.

Other research indicates that watchful waiting may be a dangerouschoice because it allows the primary tumor to progress. The hazardrate, which is defined as the probability of cancer recurrencein any given year after treatment, is not dramatically differentfor men who were treated conservatively or with surgery in thefirst 5 years after treatment.

After 10 years, however, the hazard rate falls dramatically amongmen treated with surgery, and it rises among men followed withsurveillance. "This is a very strong suggestion that gettingrid of the primary tumor really does alter the natural historyof the disease," reported Peter T. Scardino, MD, professorand chairman, Scott Department of Urology, Baylor College of Medicine,Houston.

Two radiotherapy series published by Stanford University and MemorialSloan-Kettering Cancer Center also lead to the conclusion that"if the local prostate cancer is not controlled, the patientpays the price of progressive development of tumor, later spread,metastasis, and ultimately death from cancer," Dr. Scar-dinosaid.

On the other hand, because only about 4% of the population isat risk of death from prostate cancer, Dr. Thompson contends thatthe impact of the disease on society is extremely low and, therefore,morbidity should be of prime importance. "If any treatmentother than surveillance is offered, physicians and patients mustbe assured that the impact on quality of life is minimal,"he said.

Although prostatectomy has had a major adverse effect on the qualityof patients' lives in the past, the risk of serious side effectsfrom prostatectomy is on the decline, Dr. Scardino said. Among3,500 patients managed surgically in major prostate cancer treatmentcenters, only 0.11% died, fewer than 1% had rectal injuries, 2.4%had thrombotic complications, 6% had anastomotic stricture, 13%were incontinent, and 2.7% had severe incontinence, he said.

In a series of 315 patients from Baylor College of Medicine whohad been followed for at least a year after radical prostatectomy,only 7% had severe incontinence and 7% had stress incontinence,he said. After modifications in surgical techniques were made,the rate of incontinence fell to 6%, and the duration of incontinencedropped from a median of 4.5 months to 1.7 months.

Using nerve-sparing operative techniques, surgeons also have beenable to reduce the rate of impotence. "There is no questionthat the most important factor in preserving potency is the degreeof damage to the neurovascular bundle. If you resect the bundle,there will be almost no potency. If you resect part of the bundle,the potency rate decreases significantly," Dr. Scardino said.

He noted that prior potency, age, and the clinical or pathologicalstage of the tumor, which all affect potency after prostatectomy,are beyond the control of the physician. "But as surgeonswe can control how much damage we do to the neurovascular bundle,"he added.

Advancements in radiotherapy likewise have reduced the side effectsof treatment. Gerald E. Hanks, MD, professor and chairman of theDepartment of Radiation Oncology, Fox Chase Cancer Center, Philadelphia,has been using conformal radiation since 1989.

This technique protects normal tissue and bombards cancerous areaswith radiation daily throughout a formal course of therapy. In374 of 632 patients, conformal therapy has decreased the numberof acute symptoms associated with radiotherapy by about 50%, hesaid.

Even after the dosage of radiation was increased to 75 Gy, conformaltherapy caused few side effects. The primary problem associatedwith high-dose radiation is rectal bleeding. However, only 5.7%of patients who received high-dose conformal therapy at Fox Chasehad rectal bleeding requiring laser therapy or prolonged use ofmedication, and none of the patients had a colostomy or incontinence,Dr. Hanks said.

Conformal radiotherapy appears to be increasing the extent ofcontrol of the disease. While only 39% of patients responded toconventional radiotherapy, more than 50% responded to conformalradiotherapy as shown by a PSA level that was less than 1.5 ng/mLand was not rising 4 to 5 years after treatment, Dr. Hanks reported.

Downside of Radiotherapy

"Decreased morbidity is one of the most powerful advantagesof radiotherapy," Dr. Scardino acknowledged. "Patientsavoid any operation and may be able to work full-time during radiotherapy.There is little or no risk of incontinence, and although it isnot clear what proportion of patients become impotent eventually,impotence develops more slowly with radiotherapy than with surgery,"Dr. Scardino said.

The major problem with radiotherapy, however, is the lack of certaintythat the treatment will eradicate the cancer. Investigators haveno clear definition of the PSA level that should be achieved afterradiotherapy and when this level should appear, Dr. Scardino said.

One large series of patients indicated that 64% had no evidenceof a rising PSA level 5 years after radiotherapy. In other series,however, only 40% of patients met this criterion.

Radical prostatectomy is still the most effective interventionat this time for long-term cure of localized prostate cancer,Dr. Scardino said. Citing two of many clinical studies of prostatectomy,he noted that localized prostate cancer was completely eradicatedafter 5 years in 80% of more than 500 patients who underwent radicalprostatectomy at Baylor, and that 70% of men who had surgery atJohns Hopkins Medical Center were free of metastatic cancer at5 years.

Nevertheless, Dr. Thompson pointed out, approximately 30% of menwho have supposedly curative radical surgery require additionaltherapy within 3 years.

Dr. Hanks believes that prostatectomy has not been shown to besuperior to radiation therapy. He said that the low rates of deathand severe side effects among surgery patients have been reportedat the best treatment centers.

"The mortality, morbidity, and cancer control outside ofthe major treatment centers are unknown, and there is no knowledgeof what happens in the greater USA," Dr. Hanks said. Lookingat data from the Medicare population, the death rate followingradical prosta-tectomy is up to 2%, incontinence is 6%, stressincontinence is 30%, and impotence is 60%, he added.

'Everything Is Changing'

After 10 years during which treatment for prostate cancer remainedessentially unchanged, scientists are now beginning to identifythe factors that influence outcomes. "Everything is changing;what we knew last year just doesn't apply this year," Dr.Hanks said.

Physicians will have to continue to wait for definitive conclusionsregarding the benefits of radiotherapy and prosta-tectomy whileinvestigators apply new measurements of comparison between thetwo interventions.

Until the randomized Prostate Cancer Intervention vs ObservationTrial (PIVOT) is completed, physicians will not have a solid basisof comparison regarding the value of watchful waiting and prostatectomy.However, Dr. Hanks predicted: "We will answer the questionof which treatment for localized prostate cancer is better, withinthe next 5 years."