Vaccine for men with advanced prostate cancer shows promise

May 15, 2008

The advent of the taxanes has been an important recent breakthrough in the treatment of advanced prostate cancer, and the availability of these new chemotherapeutic agents has been accompanied by an explosion in research investigating new protocols, especially involving multimodal regimens combining a taxane with immunotherapy or hormonal therapy.

Key Points

The advent of the taxanes has been an important recent breakthrough in the treatment of advanced prostate cancer, and the availability of these new chemotherapeutic agents has been accompanied by an explosion in research investigating new protocols, especially involving multimodal regimens combining a taxane with immunotherapy or hormonal therapy. At the AUA annual meeting in Orlando, FL, urologists can expect to hear more about these new approaches to improve outcomes for men with advanced prostate cancer.

While the vaccine research represents promise for the future, researchers are continuing to focus on issues that hold immediate pragmatic interest. Within this realm, a number of reports at the meeting relate to existing challenges, including the management of men found to have regional lymph node involvement at the time of radical prostatectomy, the efficacy of salvage cryotherapy for men who are primary radiotherapy failures, and strategies for mitigating adverse effects accompanying androgen deprivation therapy (ADT).

He noted that vaccines appear to have the greatest potential for efficacy when the tumor burden is low, and that has great relevance to clinical practice, considering that recurrences are being detected earlier now than ever before.

"Although chemotherapy with the taxanes has been an important advance, this chemotherapy is not a home run. Vaccine therapy, especially approaches that aim to induce the host immune response against multiple tumor-associated antigens, has enormous curative potential, and we can look forward to much more research in this area," Dr. Thrasher said.

At the AUA meeting, researchers will be reporting findings from a trial evaluating the toxicity, immune responses, changes in PSA doubling times, and patient survival among men with stage D2 or D3 prostate cancer treated with one of three doses of an adenoviral/PSA vaccine. Watch for findings about the vaccine's safety and its ability to induce an immune response to PSA.

Lymph node involvement

The question of how well men fare after surgery when low-volume lymph node involvement is discovered at the time of radical prostatectomy will be addressed by several groups of investigators. Overall, their reports indicate favorable long-term outcomes can be achieved in a significant proportion of men with administration of adjuvant hormonal or radiation treatment combined with extended lymph node dissection and radical prostatectomy.

One study comparing groups of men whose surgery was abandoned or continued after being found to have positive lymph nodes during radical prostatectomy showed better clinical progression-free survival and prostate cancer-specific survival when the surgery was completed. Researchers examining a multi-institution patient cohort also confirmed that excellent clinical outcomes could be achieved in node-positive patients who had radical prostatectomy with pelvic lymph node dissection and adjuvant treatments. These researchers went on to use their data to develop a nomogram to predict prostate cancer-specific survival within this patient population.

"This is an area of interest for practicing urologists considering that traditional teaching has been to abandon surgery when involvement of regional lymph nodes is found intraoperatively," Dr. Thrasher said. "These reports indicate long-term survival can be achieved in select patients with low-volume nodal disease."

Managing effects of ADT

Management of side effects of hormonal therapy represents another important focus of research at the meeting. Various groups will be reporting on their positive experiences using acupuncture to reduce hot flashes, tamoxifen (Nolvadex, Soltamox) as prophylaxis against the development of breast enlargement and tenderness, and zoledronic acid (Zometa) to prevent osteoporosis in men receiving prolonged ADT or who are otherwise at high risk for significant bone loss.

"Caring for men suffering from adverse effects of hormonal therapy is a challen-ge faced by urologists in daily practice," Dr. Thrasher pointed out. "Up to 90% of prostate cancer patients treated with hormone therapy are bothered by hot flashes, and gynecomastia and tenderness are common and very worrisome to patients. Information on strategies for alleviating these treatment-related side effects is of critical importance to the practicing urologist."

The management of men with locally recurrent disease after primary radiation therapy represents another clinical challenge. Thus, positive information being reported on 10-year outcomes of salvage cryotherapy is welcome news, noted Dr. Thrasher.

"Treatment with newer cryotherapy technology appears to be safer and more effective compared with use of previous generation equipment, but there has been a lack of long-term outcomes data on its use in patients who are radiotherapy failures. This initial information is encouraging in suggesting salvage cryotherapy can be a viable strategy," he said.