Prostate Cancer: Of Turtles, Birds, and
Rabbits…
Frank Hinman, Jr, alluded to our limited knowledge of prostate
cancer behavior by using the metaphor of the "barnyard pen." To paraphrase his
statement, prostate cancer was compared to a barnyard pen in which there were turtles
going nowhere (incidental, nonlethal cancers), rabbits ready to hop out any time
(potentially lethal cancers that might benefit from treatment), and birds (cancers that
are beyond cure at diagnosis).
We still know very little regarding the mechanisms leading to the
induction, promotion, and progression of prostate cancer. We still lack the ability to
distinguish lethal from nonlethal prostate cancer. The optimal definitive treatment for
localized prostate cancer is currently controversial. When the cancer is advanced, the
disease is incurable. Despite this bleak landscape, the past decade has seen momentous
advances in the understanding of prostate cancer at different levels.
The widespread use of the serum prostate-specific antigen (PSA)
beginning in the late 1980s defined populations of men at variable risks of having
prostate cancer. This phenomenon brought a tremendous increase in the annual incidence of
newly diagnosed prostate cancer cases in the early 1990s. This trend has recently
reverted, and now we are seeing a decrease in this incidence.1 Mortality from
prostate cancer has decreased as well.2 Some speculate that this decrease in
mortality is a consequence to the use of PSA and early detection. An alternative
explanation may be that advanced prostate cancer is been detected earlier than in the past
(PSA failure after local treatment). Many patients are treated at this stage with hormonal
therapy. Is hormonal therapy the real culprit in improving survival?
Should we screen for prostate cancer? Early detection is more
precise now than it was only five years ago. The introduction of the percent-free PSA
defines better which men may benefit from a prostate biopsy when the total serum PSA is
marginally elevated.3 A large US screening trial makes a compelling argument
for screening. An improvement in the detection of clinically significant, earlier cancers
when men are followed up with yearly PSAs is reported.4 A recent Canadian study
by Labrie et al5 presented at this year’s annual meeting of the American
Society of Clinical Oncology and the American Urological Association reports improved
survival in men followed with periodic determinations of PSA compared with a non-followed
control group. Statisticians have cautioned on the methodology of the study and the
disproportionate increase in survival therein reported.
Scandinavian investigators have recently published conflicting
reports arguing both excellent cancer-specific survivals and an unacceptable high risk of
progression in men with prostate cancer follow-up by observation.6-8 A selected
group of elderly men with newly diagnosed early prostate cancer will definitely benefit
from non-intervention.
Recent series report9,10 excellent long-term outcomes
from both surgery and brachytherapy for early prostate cancer. Complication rates
associated with these procedures have markedly decreased in the past 10 years, along with
an improvement in quality of life.
This issue of Cancer Control highlights several timely issues
regarding prostate cancer.
Accurate staging of prostate cancer is critical to establish optimal
treatment. Current imaging modalities have improved in accuracy but still are limited in
both sensitivity and specificity. Michael J. Manyak, MD, discusses the use of monoclonal
antibody-derived radioimmunoscintigraphy. In selected cases, this imaging modality may
provide information not attainable by computed tomography or magnetic resonance imaging.
Claudia G. Berman, MD, and Norman J. Brodsky, MD, summarize advances in these imaging
modalities and their current use in the staging of prostate cancer.
Accurate histopathologic diagnosis is pivotal both at the time of
diagnosis and follow-up of patients with cancer. William M. Murphy, MD, discusses the
complexities associated with histologic interpretation and unclear terminology. He
advocates a concept keen to our institution: the pooling of knowledge from each individual
involved in the care of a particular patient to create a coordinated approach to patient
care at the point of delivery.
Molecular techniques have been recently developed to assess for
circulating tumor cells. This "molecular staging" of prostate cancer uses the
reverse transcriptase polymerase chain reaction (RT-PCR) to detect PSA or PSMA containing
cells in the bloodstream. The clinical application of this concept is currently
controversial. Jose G. Moreno, MD, and Leonard G. Gomella, MD, discuss the limitations of
the technology and the need for a better understanding of the biology of tumor cells
present in the circulatory system.
Hormonal therapy has been the mainstay for the treatment of advanced
prostate cancer for more than 50 years. Many questions remain unanswered regarding the
timing, completeness, and extent of androgen blockade. When the cancer becomes refractory
to hormonal treatment, current chemotherapy is ineffective. Randall Rago, MD, reviews the
use of hormonal therapy in different clinical circumstances and the current status of
chemotherapy in the management of advanced prostate cancer.
Finally, gene therapy appears to have come of age. Still in its
embryonic stage, this treatment modality is now a reality. Several institutions around the
country are actively experimenting with this approach. Mohammad R. Nowroozi, MD, and Louis
L. Pisters, MD, present a state-of-the-art report and summarize the available protocols to
date with gene therapy for the treatment of prostate cancer.
Julio M. Pow-Sang, MD
Program Leader, Genitourinary Oncology Program
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida
References
1. Landis S, Murray T, Bolden S, et al. Cancer statistics, 1998. Ca Cancer J Clin.
1998;48:6-29.
2. Hoeksema M, Law C. Cancer mortality rates fall: a turning point for the nation. J
Natl Cancer Inst. 1996;88:1706-1707.
3. Catalona W, Smith D, Wolfert R, et al. Evaluation of percentage of free serum
prostate-specific antigen to improve specificity of prostate cancer screening. JAMA.
1995;274:1214-1220.
4. Catalona W, Richie J, Ahmann F, et al. Comparison of digital rectal examination and
serum prostate specific antigen in the early detection of prostate cancer: results of a
multicenter trial of 6,630 men. J Urol. 1994;151:1283-1290.
5. Labrie F, Dupont A, Candas B, et al. Decrease of prostate cancer death by screening:
first data from the Quebec prospective and randomized study. Proc Annu Meet Am Soc Clin
Oncol. 1998;17:4. Abstract.
6. Johansson J, Holmberg L, Johansson S, et al. Fifteen-year survival in prostate
cancer: a prospective, population-based study in Sweden. JAMA. 1997;277:467-471.
7. Gronberg H, Damber J, Jonsson H, et al. Patient age as a prognostic factor in
prostate cancer. J Urol. 1994;152:892-895.
8. Aus G, Pileblad E, Hugosson J. Impact in competing mortality on the cancer-related
mortality in localized prostate cancer. Urology. 1995;46:672-675.
9. Ohori M, Goad J, Wheeler T, et al. Can radical prostatectomy alter the progression
of poorly differentiated prostate cancer? J Urol. 1994;152:1843-1849.
10. Ragde H, Elgamal A, Snow P, et al. Ten-year disease free survival
after transperineal sonography-guided iodine-125 brachytherapy with or without 45-gray
external beam irradiation in the treatment of patients with clinically localized, low to
high Gleason grade prostate carcinoma. Cancer. 1998;83:989-1001.
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