Researchers take important step with prostate cancer vaccine

August 15, 2008

Research presented on advanced prostate cancer gives urologists information they can use now in daily practice and highlights an important step forward in the development of vaccine therapy.

Key Points

Following prostatectomy, initial observation followed by delayed salvage radiation therapy is optimal for patients with positive surgical margins and extracapsular tumor extension, Select patients with seminal vesicle invasion also can benefit. Lymph node-positive patients are unlikely to benefit from the therapy.

In men found to have positive surgical margins or extracapsular extension at the time of prostatectomy, most practicing urologists are waiting to refer patients for radiation therapy at least until continence returns and there is a rise in PSA. The information reported at this year's AUA meeting supports this approach, Dr. Thrasher said.

"Starting immediate therapy is not altering the patient's course from a disease-specific standpoint. Delaying treatment minimizes over-treatment and, as the data presented at this year's AUA meeting showed, it is still beneficial," he said.

Among prostate cancer patients with involvement of regional lymph nodes, those who still underwent prostatectomy had more favorable progression-free survival and cancer-specific survival than did the patients in whom the prostatectomy was abandoned.

This important message provides guidance on how to proceed when patients are identified intraoperatively to have low-volume lymph node involvement. For years, it has been taught that prostatectomy should be abandoned in this situation, where "the cat is already out of the bag," Dr. Thrasher noted.

On the other hand, some urologists have believed that surgery should be completed, based on the results of Eastern Cooperative Oncology Group study EST 3886, which showed survival benefits for immediate versus deferred ADT in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy.

"ECOG EST 3886 was not really designed to answer the question of whether there is a benefit for completing prostatectomy," Dr. Thrasher said. "Other studies support proceeding with the operation, although their populations were small.

"The relevant new information reported at the AUA meeting comes from several investigations, including a multi-institution study, and importantly, provides outcomes data that specifically address survival."

A phase I study of an adenovirus/PSA vaccine found it to be safe and effective in 32 patients. In another vaccine study, single-dose 177Lu-J591 was well tolerated and demonstrated anti-tumor activity in patients with metastatic, progressive, androgen-independent prostate cancer.

Almost a decade ago, a flurry of research was presented at the AUA annual meeting on adenovirus- and retrovirus-based therapeutic vaccines for prostate cancer. In the interim, little information has been presented on this topic. However, hope is being renewed by results of animal studies and this first clinical trial from the University of Iowa that reports that a vaccine targeting PSA-producing cells is safe and may be very effective in reducing PSA.

"Currently, the Iowa researchers and groups from other institutions are looking at designing phase II studies, and it is very exciting to see vaccine research coming to fruition," Dr. Thrasher said.

Dr. Thrasher anticipates the vaccine would be most beneficial in men with PSA recurrence after definitive treatment.

"Having a viral vector that can seek out and destroy cancer cells in men with a very low PSA and low-volume cancer not detectable by imaging modalities would be tremendously beneficial, considering the number of men who develop a PSA recurrence after definitive treatment," he said.

In a large study of pa-tients who received androgen deprivation therapy for longer than 1.5 years, dementia and chronic pulmonary disease were the only morbidities associated with ADT.

The importance of this take-home message is that it reinforces the need to use ADT judiciously. Previous studies have identified a number of serious side effects associated with ADT, including cardiovascular disease and diabetes. The information presented at the 2008 AUA meeting adds chronic pulmonary disease and cognitive problems to the list.

"There have been several articles suggesting that ADT is overused and also misused in patients with early-stage prostate cancer who are not in a high-risk group," Dr. Thrasher said. "This is additional information to suggest that the practice may not be safe. Urologists should keep in mind that ADT is not innocuous, so it should be added only after careful consideration of whether it represents a meaningful addition to existing treatment."