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 :
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 .
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
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 .
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.
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
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.
1. Johansson JE, Adami HO, Andersson SO, et al: High 10 year survival
rate in patients with early, untreated prostatic cancer. JAMA
2. Johnansson JE: Expectant management of early stage prostatic
cancer: Swedish experience. J Urol 152:1753, 1994.
3. Warner J, Whitmore WF Jr: Expectant management of clinically
localized prostatic cancer. J Urol 152:1761, 1994.
4. Cowen ME, Chartrand M, Weitzel WF: A Markov model of the natural
history of prostate cancer. J Clin Epidemiol 47:3, 1994.
5. Milestone BN, Seidmon EJ: Endorectal coil magnetic resonance
imaging of prostate cancer. Semin Urol 13:113, 1995.