Management of Locally Advanced Prostate Cancer

The treatment of advanced prostate cancer continues to be an enigma. Every few years, it seems, a new variation in treatment is espoused and offered to the public. To date, two trends seem to have emerged: For men under 70 years of age, there seems to be a consensus that definitive treatment should be pursued for low-grade, low-stage, localized tumors. Prostatectomy or radiation therapy may cure or at least increase survival; for men over age 70, less vigorous treatment is often the preferred choice [1,2]. Nevertheless, outside of these two points of agreement, many other controversial questions remain and will persist for some time.

The Prostate Cancer Intervention vs Observation Trial (PIVOT) is a randomized investigation that will compare radical prostatectomy to observation in patients with early-stage disease. Perhaps, this clinical trial will answer two crucial questions posed in 1994 by Drs. Warner and Whitmore [3]:

1) When cure is possible, is it necessary?

2) When cure is necessary, is it possible?

Possibly, the Markov model, which predicts the natural history of prostate cancer, can help us find definitive answers and ultimately guide patients into the optimal treatment program that will maximize their survival and quality of life [4].

The article by Mordkin et al represents a timely overview of the management of locally advanced prostate cancer. Although the paper does, indeed, address all of the significant treatments, it is definitely slanted toward the radiation oncologist's point of view.

The authors nicely cover the natural history and staging of locally advanced disease, demonstrating the difficulty in accurately estimating disease extent. The shortcomings of digital rectal examination (DRE) and transrectal ultrasound (TRUS) are due to the lack of precise detail with the former and the inability of the latter to yield a diagnosis. The DRE is helpful in recognizing the presence of cancer and its possible extent, while TRUS serves as an excellent guide for needle biopsy to confirm periprostatic disease extension.

Computed tomography has never been shown to be an accurate diagnostic tool for prostate cancer. Magnetic resonance imaging (MRI) with an endorectal coil, with or without the use of intravenous gadolinium, has improved staging accuracy, but newer hardware and improved pulse sequences are necessary to raise the accuracy of MRI interpretation of localized extraprostatic disease [5].

Treatment Options

Surgical treatment without neoadjuvant hormonal therapy will too often result in a pathologic finding of positive surgical margins. On the other hand, the addition of neoadjuvant hormonal treatment will result in a decrease in the volume of the prostate and a decrease in serum prostate-specific antigen

(PSA) to a normal or undetectable level, and yet the tumor is not eradicated. Thus, the concept of downstaging should be abandoned and replaced with the more realistic term, "downsizing."

Radiation therapy has been improved by the availability of conformal external-beam techniques and conformal interstitial boost treatments. Theoretically, focused higher doses of radiation to the prostate should improve local control; however, so far, documentation of this is lacking. Again, cytoreductive hormonal therapy shows promise, but long-term follow-up is wanting.

Lastly, cryotherapy has been reintroduced as a treatment modality after a 15-year hiatus. This treatment, too, shows promise. Pretreatment with hormones shrinks larger glands, which allows for a better freeze of the entire gland. However, aggressive therapy, especially by the less experienced physician, can lead to significant complications. Other issues concerning cryo- ablation of the prostate, such as the correct temperature for the urethral warmer, cryoprobe placement, and thermocouple monitoring, still need refinement.

Summary

In summary, the authors adequately discuss the efficacy of each treatment modality for locally advanced prostate cancer. As they note, the addition of hormonal therapy to other treatments may offer some therapeutic improvement. However, we must await survival data to confirm which therapy will ultimately prove to be most effective.

Further improvements in the treatment of this disease will continue to be made. The advent of molecular markers, as well as newer and more accurate tumor markers, will be beneficial, and some form of gene therapy may also have clinical applications. At the very end of the article, the authors astutely comment that patients with advanced prostate cancer should be directed to institutions conducting prospective trials, which ultimately may improve patient survival and quality of life.