Download Comparing the Age at Prostate Cancer Diagnosis in Humans and

have a long way to go before reliable
clinical utility can be achieved.
CORRESPONDENCE
JEROME J. DECOSSE
Comparing the Age at Prostate
Cancer Diagnosis in Humans
and Dogs
WANDA J. CENNERAZZO
References
Re: A Quality-Adjusted Time
Without Symptoms or Toxicity
(Q-TWiST) Analysis of
Adjuvant Radiation Therapy
and Chemotherapy for
Resectable Rectal Cancer
To our knowledge, Gelber et al. (7)
have provided the first quantitative
scrutiny of quality-of-life management
of patients treated for locally advanced
rectal cancer. The authors conclude,
"Use of combined chemotherapy and
radiation therapy as an adjuvant to
surgery for patients with poor-prognosis
resectable rectal cancer is justified." To
which may be added—in comparison
with postoperative adjuvant radiation
therapy alone. There also appears to be
an assumption, which generally conforms with the literature, that adjuvant
postoperative radiation therapy alone
does not improve survival.
However, the usual treatment decision confronting the patient is combined treatment versus no treatment. In
the absence of a comparison, have the
authors examined their data by deleting
the impact of those toxic events or
delayed reactions attributable to radiation therapy in the control group? Such
complications, including death, were
cited in the published manuscript from
which the current study is derived (2).
Reasonably predictive estimates of
quality of life after various treatment
options are valuable in helping the
patient with rectal cancer to make difficult choices. By embracing the side effects of treatment alternatives, Gelber et
al. are to be congratulated for their accomplishment in this difficult field.
However, quality of life has many elements. Some dimensions, such as performance status and economic considerations, can be quantified.
Other elements, such as pain, psychological factors, and genitourinary function, are more difficult to integrate. We
1686 CORRESPONDENCE
(/) Gelber RD, Goldhirsch A, Cole BF, Wieand
HS, Schroeder G, Krook JE. A quality-adjusted time without symptoms or toxicity (QTWiST) analysis of adjuvant radiation therapy
and chemotherapy for resectable rectal cancer.
J Nad Cancer Inst 1996;88:1039-45.
(2) Krook JE, Moertel CG, Gunderson LL,
Wieand HS, Collins RT, Beart RW, et al. Effective surgical adjuvant therapy for high-risk
rectal carcinoma [see comment citations in
Medline]. N Engl J Med 1991 ;324:709-15.
Note
Correspondence to: Jerome J. DeCosse, M.D.,
Department of Surgery, New York Hospital-Cornell Medical Center, 525 East 68th St., Suite F1917, New York, NY 10021.
Response
We thank Dr. DeCosse and Ms. Cennerazzo for their compliments regarding
our work. The requested examination of
our data can be performed simply by
taking the average months in TOX (i.e.,
time with toxicity) associated with the
radiation therapy-alone arm and putting
them into the TWiST clinical health
state for the analysis. The results in this
case continue to demonstrate a substantial advantage for the combined-modality approach. This analysis, however, is
based on the assumption that radiation
therapy alone does not improve diseasefree survival or overall survival. We
agree that more evaluations that incorporate aspects of quality of life into
treatment decision-making are needed.
RICHARD D. GELBER
ARON GOLDHIRSCH
BERNARD F. COLE
JAMES E. KROOK
Note
Correspondence to: Richard D. Gelber, Ph.D.,
Division of Biostatistics, Dana-Farber Cancer Institute, 44 Binney SL, Boston, MA 02115.
Prostate cancer is the most frequently
diagnosed noncutaneous cancer in U.S.
men and kills more than 40 000 men annually in this country (7). It is interesting that the dog is the only nonhuman
species in which spontaneous prostate
cancer occurs frequently (2). Clinically
apparent prostate cancer in pet dogs exhibits aggressive biologic behavior, with
metastasis to regional lymph nodes or
lungs present frequently at the time of
diagnosis (3,4). Canine prostate cancer
also shares with its human counterpart a
high propensity for skeletal metastasis.
Recently, we documented that highgrade prostatic intraepithelial neoplasia
(PIN), the likely precursor of many
human prostate cancers (5), occurs
spontaneously in the canine prostate in
association with invasive carcinoma (<5).
Canine PIN shares many of the morphologic and immunophenotypic features of human PIN, including basal
layer disruption, an increased proliferative index, and increased microvessel
density compared with that of benign
epithelium (6).
Our work (6,7) suggests that pet dogs
offer a naturally occurring animal model
to study factors that regulate the initiation and progression of prostate cancer.
Recently, we developed an algorithm to
convert the chronologic age of dogs to
physiologic age in human years. This algorithm is based on mortality data from
more than 23 000 pet dogs in the computerized Veterinary Medical Data Base
and takes into consideration breed- and
body size-specific differences in life expectancy (8). The purpose of this study
was to compare the age at prostate cancer diagnosis in dogs with previously
published age-specific incidence data
from humans.
The age at diagnosis of spontaneous
prostate cancer in 686 pet dogs was obtained from the Veterinary Medical
Data Base. For each dog, chronologic
age at diagnosis was converted to physiologic age expressed in human years by
use of the following algorithm (8):
Journal of the National Cancer Institute, Vol. 88, No. 22, November 20, 1996
Physiologic age (human
{[(-0.0013 * X) + 0.0221]
{[(-0.0285 * X) - 0.107]
{[(0.2911 * X) + 4.9979]
(-3.6437 * X) + 37.4,
years)
* C3}
* C2}
* C)
=
+
+
+
where X is the breed- or body sizespecific median age at death (years) and
C is the chronologic age of dogs in
years. Physiologic age at diagnosis for
the 686 dogs with prostate cancer was
compared with the age of 110 men diagnosed with prostate cancer prior to the
use of serum prostate-specific antigen
screening (9). These human data were
selected for comparison because the
canine prostate cancers were diagnosed
following the onset of clinical signs,
rather than by screening with a biochemical marker.
The physiologic age at prostate cancer diagnosis, expressed in human
years, was similar between the two
species (Fig. 1). In both species, prostate
cancer was uncommon in young males.
Only 4% of cases occurred in dogs
younger than the equivalent of 45
human years; only 1% of cases in
humans were diagnosed before the age
of 50 years. Mean and median
physiologic ages at the diagnosis of
prostate cancer in dogs, expressed in
human age equivalents, were 67 years
and 73 years, respectively. Mean age at
diagnosis for the men with prostate cancer was 70 years. Forty-four percent of
prostate cancers were diagnosed in dogs
at greater than 70 years of physiologic
age. Similarly, 56% of the human cancers were diagnosed in men 70 years of
age or older.
Because dogs of small body size (versus large body size) or mixed breed
(versus pure breed) have increased longevity (8), we have used an algorithm
that standardizes the chronologic age of
dogs of different breeds and body sizes
to physiologic age expressed in human
D Dog
• Human
Fig. 1. Age at prostate cancer
diagnosis in dogs (n = 686)
and men (n = 110) diagnosed
without use of serum prostate-specific antigen screening. Human data from
Jacobsen et al. (9).
<50
50-69
70-79
>80
Physiological age at diagnosis (years)
years. This analysis has important implications for comparative oncology research, because this approach can be
used to determine the influence of
physiologic age on the development of
prostate cancer and other naturally occurring cancers in pet dogs.
We conclude that the development of
spontaneous prostate cancer in dogs and
humans is similarly influenced by age.
Appropriate in vivo animal models are
needed to study factors that regulate the
development and progression of prostate
cancer. Our data further strengthen the
hypothesis that pet dogs may serve as a
relevant model to increase our understanding of prostate carcinogenesis.
DAVID
GARY J.
DAVID G.
LARRY T.
J. WATERS
PATRONEK
BOSTWICK
GLICKMAN
(3) Leav I, Ling GV. Adenocarcinoma of the
canine prostate. Cancer 1960;22:1329-45.
(4) Bell FW, Klausner JS, Hayden DW, Feeney
DA, Johnston SD. Clinical and pathologic
features of prostatic adenocarcinoma in
sexually intact and castrated dogs: 31 cases
(1970-1987). J Am Vet Med Assoc 1991;
199:1623-30.
(5) Montironi R, Bostwick DG, Bonkhoff H,
Cockett AT, Helpap B, Troncoso P, et al.
Origins of prostate cancer. Cancer 1996;78:
362-5.
(<5) Waters DJ, Hayden DW, Bell FW, Klausner
JS, Qian J, Bostwick DG. Prostatic intraepithelial neoplasia in dogs with spontaneous
prostate cancer. Prostate. In press.
(7) Waters DJ, Bostwick DG. Prostatic intraepithelial neoplasia occurs spontaneously in
the canine prostate. J Urol. In press.
(S) Patronek GJ, Waters DJ, Glickman LT. Comparative longevity of pet dogs and humans:
implications for gerontology research. J
Gerontol. In press.
(9) Jacobsen SJ, Katusic SK, Bergstralh EJ,
Oesterling JE, Ohrt D, Klee GG, et al. Incidence of prostate cancer diagnosis in the
eras before and after serum prostate-specific
antigen testing. JAMA 1995;274:1445-9.
Notes
References
(/) Wingo PA, Tong T, Bolden S. Cancer statistics, 1995 [published erratum appears in CA
Cancer J Clin 1995;45:127-8]. CA Cancer J
Clin 1995;45:8-30.
(2) Rivenson A, Silverman J. The prostatic carcinoma in laboratory animals: a bibliographic
survey from 1900 to 1977. Invest Urol 1979;
16:468-72.
Journal of the National Cancer Institute, Vol. 88, No. 22, November 20, 1996
Affiliations of authors: D. J. Waters (Department of Veterinary Clinical Sciences), G. J.
Patronek, L. T. Glickman (Department of Veterinary Pathobiology), Purdue University, West
Lafayette, IN; D. G. Bostwick, Department of
Pathology and Laboratory Medicine, Mayo Clinic,
Rochester, MN.
Correspondence to: David J. Waters, D.V.M.,
Ph.D., Purdue University, Cancer Biology
Laboratory, 1296 Lynn Hall, West Lafayette, IN
47907-1248.
CORRESPONDENCE 1687