Combo treatment in high-risk prostate cancer may reshape paradigm

August 15, 2007

The AUA take-home messages on management of localized prostate cancer.

Key Points

However, in the opinion of Richard D. Williams, MD, professor and chairman, department of urology, University of Iowa, Iowa City, information on the use of neoadjuvant treatment with hormone therapy and chemotherapy ranks as the most important message because it is a first encouraging report of a possible new paradigm for improved disease management.

Treatment with neoadjuvant hormone therapy and chemotherapy with docetaxel (Taxotere) prior to radical prostatectomy in men with high-risk prostate cancer led to complete pathologic response in two patients and a microfocus of disease in 12 patients.

"Those studies should investigate the role of chemotherapy as neoadjuvant treatment for downstaging locally extensive disease prior to surgery, as well as whether docetaxel has benefit as adjuvant treatment postprostatectomy in men with poor prognostic features, such as high-grade or high-volume cancer, positive margins, or positive seminal vesicles. Importantly, confirmation of the initial anecdotal reports needs to be obtained in randomized studies," Dr. Williams said.

He also noted that, while the anatomic findings in this first study are very encouraging and suggest that patients treated in this manner will ultimately benefit with a decreased risk of biochemical or tumor recurrence, those longer-term outcomes also need to be demonstrated in rigorous prospective trials.

"At present, this report does not provide a basis for changing practice. Only if future studies confirm that neoadjuvant chemotherapy improves disease stage and grade and decreases recurrence rates would patients with high-risk disease be considered for this treatment," Dr. Williams said.

After a mean 2-year follow-up of men treated with primary cryoablation, biochemical recurrence-free survival was 80% based on American Society for Therapeutic Radiology and Oncology criteria. But nearly one-fourth of men who underwent post-treatment biopsy were found to have residual cancer and a high rate of erectile dysfunction.

The bottom-line message from these data is that primary cryoablation is not a very effective treatment for prostate cancer, Dr. Williams concluded. Based on only 2 years of follow-up, the reported biochemical recurrence-free survival rate has little relevance and it is unimpressive, considering that the same outcome would be expected with hormone therapy alone.

The positive biopsy rate is also unacceptably high and the association with erectile dysfunction disappointing, he noted.

"Until data from long-term studies demonstrate otherwise, cryoablation cannot be considered an equivalent alternative to standard primary therapies for prostate cancer," Dr. Williams said.

In patients undergoing unilateral nerve-sparing prostatectomy, no difference in potency rates was seen between sural nerve grafts and early penile rehabilitation. Results with sural nerve grafts during robotic prostatectomy are similar to those for unilateral nerve sparing without nerve grafts.

Urologists began using sural nerve grafts approximately 8 years ago as a strategy to improve potency rates after patients underwent radical prostatectomy. While some reports have suggested it was beneficial as a treatment, two studies reported at this year's AUA meeting refute that idea.

"Based on these data, it appears that urologists need to start thinking about new approaches for improving erectile function after radical prostatectomy when nerve-sparing surgery is not possible," Dr. Williams said.

Authors of a study to determine the reliability of PSA velocity to predict biochemical recurrence after prostatectomy found that a cutoff of 2.0 ng/mL per year provided optimal results.

These data are evidence that many aggressive, fast-growing tumors will have metastasized or extended locally prior to surgery. They do not alter the current recommendation to use a PSA velocity of 0.75 ng/mL per year as the threshold for biopsy in middle-aged men, but this new study underscores the need to follow PSA longitudinally to enable prompt treatment if the PSA level begins to rise.

"These data will not change clinical practice, but they are important for reinforcing that there is a benefit for earlier diagnosis," Dr. Williams said.

A 22-core, transrectal saturation biopsy better predicted Gleason score and tumor volume than did a standard 12-core biopsy, but neither technique accurately predicted pathologic stage.

This finding confirms that increasing the number of cores obtained results in a more accurate prediction of Gleason score, tumor volume, and prognosis. The association is intuitive because biopsy for prostate cancer, especially when only a few samples are taken, is like looking for a needle in a haystack, noted Dr. Williams.

"The less the prostate is sampled, the greater the likelihood that the biopsy will find only a small amount of tumor or will miss a site with the highest grade. In fact, after radical prostatectomy, both tumor volume and Gleason score are upgraded about 30%. So it is clear that more biopsies would be expected to provide better information," he explained.

These data support a shift toward increasing the number of cores obtained in prostate biopsy, particularly in men representing equivocal cases in which suspicion for prostate cancer remains high, despite two or three previous negative standard biopsies. While not routinely necessary, the ability to more accurately determine Gleason score and tumor volume by performing saturation biopsy would enhance the ability to make decisions about what constitutes optimal treatment for selected patients.

Adverse outcomes from prostatectomy, such as positive margin rate, biochemical failure, the need for secondary treatment, and erectile dysfunction, decrease with increasing surgical experience.

This study corroborates the findings from numerous other studies that show a relationship between the amount of surgeon experience and outcomes, and the data are not surprising.

"One reason for residency programs to exist is so newly trained physicians can perform enough surgical cases to become proficient," Dr. Williams explained. "This study takes that relationship to the next level in demonstrating that surgeons become even better as they accumulate even more experience."

These data are important to practicing urologists because patients are shopping for surgical services and are asking the physicians they visit about the number of procedures they've performed.

"A possible extrapolation of the data is that in large group practices, consideration should be given to procedural specialization, wherein a particular surgeon becomes primarily responsible for performing a given procedure," Dr. Williams said.