Management of Locally Advanced Prostate Cancer

September 1, 1996

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 treatment of advanced prostate cancer continues to be an enigma.Every few years, it seems, a new variation in treatment is espousedand 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 thatdefinitive treatment should be pursued for low-grade, low-stage,localized tumors. Prostatectomy or radiation therapy may cureor at least increase survival; for men over age 70, less vigoroustreatment is often the preferred choice [1,2]. Nevertheless, outsideof these two points of agreement, many other controversial questionsremain and will persist for some time.

The Prostate Cancer Intervention vs Observation Trial (PIVOT)is a randomized investigation that will compare radical prostatectomyto observation in patients with early-stage disease. Perhaps,this clinical trial will answer two crucial questions posed in1994 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 historyof prostate cancer, can help us find definitive answers and ultimatelyguide patients into the optimal treatment program that will maximizetheir survival and quality of life [4].

The article by Mordkin et al represents a timely overview of themanagement of locally advanced prostate cancer. Although the paperdoes, indeed, address all of the significant treatments, it isdefinitely slanted toward the radiation oncologist's point ofview.

The authors nicely cover the natural history and staging of locallyadvanced disease, demonstrating the difficulty in accurately estimatingdisease extent. The shortcomings of digital rectal examination(DRE) and transrectal ultrasound (TRUS) are due to the lack ofprecise detail with the former and the inability of the latterto yield a diagnosis. The DRE is helpful in recognizing the presenceof cancer and its possible extent, while TRUS serves as an excellentguide for needle biopsy to confirm periprostatic disease extension.

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

Treatment Options

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

(PSA) to a normal or undetectable level, and yet the tumor isnot eradicated. Thus, the concept of downstaging should be abandonedand replaced with the more realistic term, "downsizing."

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

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

Summary

In summary, the authors adequately discuss the efficacy of eachtreatment modality for locally advanced prostate cancer. As theynote, the addition of hormonal therapy to other treatments mayoffer some therapeutic improvement. However, we must await survivaldata to confirm which therapy will ultimately prove to be mosteffective.

Further improvements in the treatment of this disease will continueto be made. The advent of molecular markers, as well as newerand more accurate tumor markers, will be beneficial, and someform of gene therapy may also have clinical applications. At thevery end of the article, the authors astutely comment that patientswith advanced prostate cancer should be directed to institutionsconducting prospective trials, which ultimately may improve patientsurvival and quality of life.

References:

1. Johansson JE, Adami HO, Andersson SO, et al: High 10 year survivalrate in patients with early, untreated prostatic cancer. JAMA167:2191, 1992.

2. Johnansson JE: Expectant management of early stage prostaticcancer: Swedish experience. J Urol 152:1753, 1994.

3. Warner J, Whitmore WF Jr: Expectant management of clinicallylocalized prostatic cancer. J Urol 152:1761, 1994.

4. Cowen ME, Chartrand M, Weitzel WF: A Markov model of the naturalhistory of prostate cancer. J Clin Epidemiol 47:3, 1994.

5. Milestone BN, Seidmon EJ: Endorectal coil magnetic resonanceimaging of prostate cancer. Semin Urol 13:113, 1995.