Table of Contents
1
UI - 11525289
AU - Thurman SA; Ramakrishna NR; DeWeese TL
TI -
Radiation therapy for the treatment of locally advanced and metastatic
prostate cancer.
SO - Hematol Oncol Clin North Am 2001 Jun;15(3):423-43
AD - Department of Radiation Oncology, The Johns Hopkins University School of
Medicine, Baltimore, Maryland 21231, USA.
Radiation therapy for locally advanced PCa continues to evolve. A
current treatment recommendation for nonmetastatic, high-risk disease
includes AS combined with RT. The precise duration and sequencing of AS
has not been established but most frequently includes treatment in the
neoadjuvant, concomitant and, occasionally, adjuvant periods. As
technology allows higher doses without significant increases in
morbidity and as clinical data provide proof of a radiation dose
response, RT doses continue to escalate. The goal of therapy for
metastatic disease continues to focus on the relief of pain and the
improvement in quality of life. Multiple studies document the
significant role RT plays in achieving these goals. Focal RT and
systemic radioisotopes have become the mainstay of management in this
patient group and the development of newer isotopes that cause less
marrow toxicity will improve the therapeutic ratio and provide an
opportunity for their use with systemic chemotherapy. As molecular and
genomic technologies advance, directed targeting of critical cellular
radiation-response pathways hold the promise of improved radiation
response and individualized, tailored therapy.
2
UI - 11525293
AU - Ferrer FA; Rodriguez R
TI -
Prostate cancer gene therapy.
SO - Hematol Oncol Clin North Am 2001 Jun;15(3):497-508
AD - The James Buchanan Brady Urological Institute, The Johns Hopkins
Hospital, Baltimore, Maryland 21287-2101, USA.
Cancer-specific gene therapy is still in its infancy. Although the first
gene therapy trials were initiated in the late 1980s, it was only more
recently that the first successful treatment of a genetic disease was
reported.3 The current problems with low efficiency of gene transfer
coupled with the immunologic difficulties with certain vectors indicate
that more effort needs to be directed at the basic science of gene
transfer. Ultimately, successful cancer-specific gene therapy will
require combinations of the lessons learned from the ex vivo and in vivo
paradigms. The next generation of gene therapy trials likely will focus
on combination therapy with conventional chemotherapeutic agents,
differentiating agents, or radiation therapy. The obstacles to the
development of gene-based human therapeutics (i.e., molecular medicine)
are formidable, but the benefits are so great that eventually the
technical issues of gene transfer methodology will be worked out, and
ultimately this will become the standard of care, not only for inborn
errors of metabolism, but also for cancer.
3
UI - 11525295
AU - Obasaju C; Hudes GR
TI -
Paclitaxel and docetaxel in prostate cancer.
SO - Hematol Oncol Clin North Am 2001 Jun;15(3):525-45
AD - Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia,
Pennsylvania 19111, USA.
Although their ultimate value in prostate cancer therapy remains to be
defined in randomized trials, docetaxel and paclitaxel are active agents
in HRPC. Combination therapies using either of these taxanes plus oral
EMP show reproducible antitumor activity that appears to be greater and
more durable than that of single-agent treatment. Although the optimal
combination and schedule have not been determined, weekly paclitaxel and
EMP and docetaxel given every 3 weeks or by weekly infusion with EMP are
useful treatment options for patients with progressive HRPC. The
gastrointestinal toxicity of EMP has been reduced by intermittent rather
than continuous administration, and other toxicities may be reduced
further by use of intravenous EMP. Although there has been progress, the
median time to progression of 5 to 6 months for current taxane-based
therapies suggests that they will not have major impact on overall
survival for patients with HRPC. Greater benefit may be possible earlier
in the course of prostate cancer, and the activity of the taxane-EMP
combinations is sufficient to justify clinical trials of adjuvant or
neoadjuvant chemotherapy for selected groups of patients with locally
advanced and poor-prognosis tumors. Armed with many new molecularly
targeted agents that may interact favorably with taxanes, it should be
possible to build on current antimicrotubule regimens to improve
activity in HRPC. Taxane-EMP combinations provide a platform on which to
test additional agents that may enhance the apoptotic response or
circumvent cellular stress adaptations that confer drug resistance.
Further elucidation of signaling pathways that regulate microtubule
dynamics and programmed cell death after exposure to microtubule
inhibitors would provide a more rational guide for integrating specific
inhibitors of signal transduction with current taxane-based therapies.
Pharmacokinetic and pharmacodynamic studies will play a key role in the
development of future taxane-based therapies for prostate cancer.
4
UI - 11525297
AU - Smith MR
TI -
Complementary and alternative therapies for advanced prostate cancer.
SO - Hematol Oncol Clin North Am 2001 Jun;15(3):559-71
AD - Division of Hematology and Oncology, Massachusetts General Hospital
Cancer Center, Boston, USA. smith.matthew@mgh.harvard.edu
This article reviews complementary and alternative therapies for
advanced prostate cancer. This is not a comprehensive survey of
nontraditional therapies for prostate cancer. Rather, this review
focuses on alternative and complementary therapies with published
studies to evaluate efficacy and safety. Three areas are addressed:
alternative forms of hormonal therapy, management of side effects of
hormonal therapy, and management of skeletal complications.
5
UI - 11525298
AU - Sinibaldi VJ; Arzoomanian RZ
TI -
Clinical conduct and nursing quality of life in prostate cancer.
SO - Hematol Oncol Clin North Am 2001 Jun;15(3):573-81
AD - Medical Oncology, Genitourinary Malignancies, The Johns Hopkins
University, Baltimore, Maryland, USA.
Recent advances in cancer therapy and supportive care have increased
patient survival and improved quality of life. These advances have led
to an increase in the responsibilities of nurses caring for these
patients. Knowledge of new drugs, mode of action, expected side effects,
and benefits, including effects on QOL, are essential. Nurses are vital
to the safety and the quality of life that patients may experience while
participating in clinical trials.
6
UI - 11573856
AU - Giordano N; Nardi P; Santacroce C; Geraci S; Gennari C
TI -
Acute hepatitis induced by cyproterone acetate.
SO - Ann Pharmacother 2001 Sep;35(9):1053-5
AD - Institute of Internal Medicine, University of Siena, Italy.
Giordanon@unisi.it
OBJECTIVE: To report a case of acute hepatitis resulting from the use of
cyproterone acetate, an adjuvant treatment for prostate cancer. CASE
SUMMARY: An 87 year-old white man, admitted to surgery for prostate
cancer, received cyproterone acetate 300 mg/d orally and developed acute
hepatitis, which initially was diagnosed clinically. A liver biopsy
showed changes suggestive of acute cholestatic hepatitis. Cyprotorone
was stopped immediately, and the patient was subsequently treated with
corticosteroids. He then improved rapidly. DISCUSSION: Cyproterone
acetate is thought to be well tolerated, but some authors have reported
severe hepatic reactions, in particular acute hepatitis, fatal fulminant
hepatic failure, and hepatocellular carcinoma. The above-mentioned
hepatotoxicity represents an idiosyncratic drug reaction, probably due
to the hepatomitogen action of cyproterone, causing an increase of
hepatocytes expressing placental glutathione S-transferase, which are
considered preneoplastic elements. CONCLUSION: This case suggests the
possibility of hepatotoxicity from cyproterone.
7
UI - 11772129
AU - Harris KA; Reese DM
TI -
Treatment options in hormone-refractory prostate cancer: current and
future approaches.
SO - Drugs 2001;61(15):2177-92
AD - Urologic Oncology Program, Department of Medicine, UCSF Comprehensive
Cancer Center, University of California, San Francisco, USA.
Prostate cancer is the second leading cause of cancer mortality among
men in Western countries. The initial treatment of advanced prostate
cancer is suppression of testicular androgen production by medical or
surgical castration, but nearly all men with metastases will develop
disease progression. Patients with hormone refractory prostate cancer
(HRPC) have a median survival of approximately 18 months and no therapy
has yet demonstrated a definitive survival advantage. However, in the
past several years, a number of promising new treatment strategies have
emerged. One of the most important new treatment strategies involves
secondary hormonal manipulation after the failure of primary androgen
deprivation. This approach is predicated on the recognition that HRPC is
a heterogeneous disease and some patients may respond to alternative
hormonal interventions despite the presence of castrate levels of
testosterone. Until recently, cytotoxic chemotherapy was felt to be
relatively ineffective in the treatment of HRPC. Combination regimens
incorporating new active agents have demonstrated significant activity
in this setting, renewing interest in the use of chemotherapy to treat
HRPC. Recent advances in the understanding of prostate cancer biology
have led to the development of drugs directed against precise molecular
alterations in the prostate tumour cell. Biologic agents now in
development include those capable of altering signal transduction,
blocking angiogenesis, inhibiting cell cycle progression, and
stimulating apoptosis. In addition, many types of immune therapies are
showing promise. Evaluating these agents, and incorporating them into
existing regimens, are major goals of ongoing clinical research in
advanced prostate cancer.
8
UI - 11554628
AU - Hargreave TB; Ghosh C
TI -
Recovery of androgens after prostate cancer therapy.
SO - Clin Oncol (R Coll Radiol) 2001;13(4):289-90
9
UI - 11554629
AU - Shahidi M; Norman AR; Gadd J; Huddart RA; Horwich A; Dearnaley DP
TI -
Recovery of serum testosterone, LH and FSH levels following neoadjuvant
hormone cytoreduction and radical radiotherapy in localized prostate
cancer.
SO - Clin Oncol (R Coll Radiol) 2001;13(4):291-5
AD - Academic Department of Radiotherapy and Oncology, The Royal Marsden NHS
Trust, The Institute of Cancer Research, Sutton, UK.
mehdi.shahi-di@rmh.nthames.nhs.uk
This study was carried out to evaluate the possible long-term endocrine
effect of short-term neoadjuvant leuteinizing hormone-releasing hormone
analogue (LHRHa) administration in localized prostate cancer. A total of
419 men were treated for 3-6 months at The Royal Marsden NHS Trust by
neoadjuvant androgen suppression using monthly depot injections of LHRHa
before radical radiotherapy. Serum testosterone (852 measurements),
leuteinizing hormone (LH) (799 measurements), and follicle-stimulating
hormone (FSH) levels (801 measurements) were grouped according to their
timing in relation to hormonal treatment and then analysed. Suppression
of pituitary gonadotrophins and testosterone after the administration of
LHRHa and their recovery after cessation of the drug was clearly
observed. Median serum testosterone levels decreased from 16 nmol/l to
14 nmol/l when comparing prehormonal and follow-up phases. The same
comparison showed an increase in median serum LH and FSH levels, with
the median LH rising from 5 u/l to 8 u/l and the median serum FSH rising
from 6 u/l to 20 u/l. On long-term follow-up, three of 256 men have
remained with testosterone levels in the castrate range. Similar highly
significant results were seen in subgroup of 103 men who had both
pre-LHRHa and follow-up hormone levels analysed (P=0.012, P<0.001,
P<0.001 for testosterone, LH and FSH respectively). Our data suggest the
possibility of residual gonadal dysfunction after short-term LHRHa
administration and radical radiotherapy in localized prostate cancer.
Serum testosterone levels are restored to normal levels in the majority
of patients, with a compensatory increase in serum levels of LH.
10
UI - 11797466
AU - Popov I; Radosevic-Jelic Lj
TI -
[Prostate specific antigen (PSA) in the diagnosis and treatment of
prostate carcinoma: advances and controversies]
SO - Srp Arh Celok Lek 2001 May-Jun;129(5-6):159-62
AD - Institut za onkologiju i radiologiju Srbije 11 000 Beograd, Pasterova
14. ipopov@ncrc.ac.yu
11
UI - 11561685
AU - Dreicer R; See WA; Klein EA
TI -
Phase II trial of GM-CSF in advanced prostate cancer.
SO - Invest New Drugs 2001;19(3):261-5
AD - Department of Hematology/Oncology, Cleveland Clinic Foundation, OH
44195, USA. Dreicer@ccf.org
OBJECTIVES: Prostate-specific antigen only disease progression following
definitive therapy is significant therapeutic dilemma. The benefit of
hormonal therapy remains unproven and is associated with significant
toxicity, more pronounced with chronic use. Biochemical progression
following hormonal therapy has no standard treatment. New approaches to
the management of this subset of patients are needed. A previous study
in advanced prostate cancer demonstrated biologic activity of
granulocyte macrophage-colony stimulating factor. The purpose of this
study was to evaluate the activity of granulocyte macrophage-colony
stimulating factor in a less heavily pretreated population. MATERIALS
AND METHODS: Sixteen patients with advanced prostate cancer, 7
hormonally naive, and 9 androgen independent, were treated with
granulocyte macrophage-colony stimulating factor administered
subcutaneously at 250 microg three times a week for up to 6 months.
Prostate-specific antigen measurements were obtained every 2 weeks.
RESULTS: No patient achieved an objective response. Six patients
demonstrated a 10-15% decline in their baseline prostate-specific
antigen which was maintained during the entire treatment period. Five of
these 6 patients demonstrated a rise in their prostate-specific antigen
following study completion. Therapy was well tolerated, with only 1
grade 3 event which was not treatment-related. CONCLUSIONS: Granulocyte
macrophage-colony stimulating factor demonstrates modest biologic
evidence of activity in prostate cancer as manifested by
prostate-specific antigen response. Further investigation of the
mechanism of activity and additional clinical evaluation of this agent
seems warranted.
12
UI - 11807787
AU - Suenaga M; Soda H; Oka M; Yamaguchi A; Nakatomi K; Shiozawa K; Kawabata
TI -
S; Kasai T; Yamada Y; Kamihira S; Tei C; Kohno S
Histone deacetylase inhibitors suppress telomerase reverse transcriptase
mRNA expression in prostate cancer cells.
SO - Int J Cancer 2002 Feb 10;97(5):621-5
AD - First Department of Internal Medicine, Faculty of Medicine, Kagoshima
University, Kagoshima, Japan.
Telomerase activity is involved in cellular immortality. We have
recently demonstrated that telomerase activity is closely associated
with cell proliferation in prostate cancers. Telomerase is composed
primarily of the catalytic subunit (hTERT) and the RNA template (hTERC),
and hTERT expression is regulated by several factors such as c-MYC and
p21(Waf1). Histone deacetylase (HDAC) inhibitors are known to modulate
transcription and exhibit antiproliferative effects on cancer cells. The
present study was designed to evaluate the effects of HDAC inhibitors on
hTERT mRNA expression in prostate cancer cells. LNCaP and PC-3 cells
were treated with HDAC inhibitors, trichostatin A (TSA) and sodium
butyrate (NaB); mRNA expression and telomerase activity were evaluated
by RT-PCR and the TRAP assay, respectively. In LNCaP cells, hTERT mRNA
expression was suppressed at 1 and 3 hr after treatment with 1 microM
TSA and 4 mM NaB, respectively, followed by inhibition of telomerase
activity. The inhibition of hTERT mRNA expression preceded suppression
of cell proliferation. In PC-3 cells, TSA and NaB also inhibited cell
proliferation, hTERT mRNA expression and telomerase activity. In both
cell lines, TSA and NaB had no effect on hTERC expression, or on
expression of c-myc and p21(Waf1) mRNA. These effects of TSA and NaB
were unlikely to be consequences of cell cycle arrest, apoptosis, or
cell differentiation. Thus, HDAC inhibitors down-regulated telomerase
activity via suppression of hTERT mRNA expression. Our study identified
a novel mechanism for the antiproliferative effects of HDAC inhibitors
on prostate cancer cells. Copyright 2001 Wiley-Liss, Inc.
13
UI - 11693901
AU - Kupelian PA; Willoughby TR
TI -
Short-course, intensity-modulated radiotherapy for localized prostate
cancer.
SO - Cancer J 2001 Sep-Oct;7(5):421-6
AD - Department of Radiation Oncology, Cleveland Clinic Foundation, Ohio
44195, USA.
PURPOSE: The purpose of this study was to compare the toxicity,
particularly rectal, between short-course, intensity-modulated
radiotherapy (SCIM-RT) delivering 70 Gy in 28 fractions and
three-dimensional conformal radiotherapy (3D-CRT) delivering 78 Gy in 39
fractions. MATERIALS AND METHODS: A total of 191 patients were treated
with SCIM-RT. Seventy Gy was delivered using five intensity-modulated
fields via a Varian dynamic multileaf collimator. The BAT transabdominal
ultrasound system was used for localization. The comparison group
consisted of 101 contemporary cases treated with 3D-CRT to 78.0 Gy (2.0
Gy per fraction). The study sample therefore comprised 292 cases.
Seventy Gy in 28 fractions was equivalent to 78 Gy in 39 fractions for
late-reacting tissues, according to the linear quadratic model. The
median follow-up was 9 months. Radiation Therapy Oncology Group toxicity
scores were used. RESULTS: The rates of acute rectal Radiation Therapy
Oncology Group toxicity scores 0, 1, 2, and 3 were 30%, 55%, 14%, and
0%, respectively, with SCIM-RT, versus 14%, 67%, 19%, and 0%,
respectively, with 3D-CRT. The rates of acute urinary toxicity scores 0,
1, 2, and 3 were 17%, 62%, 20%, and 1%, respectively, with SCIM-RT,
versus 22%, 58%, 20%, and 0%, respectively, with 3D-CRT. To date, only
two patients who underwent SCIM-RT had grade 2 late urinarytoxicity. No
grade 3 late urinary or rectal complications occurred with SCIM-RT. The
actuarial late rectal grade 2 toxicity observed at 18 months was 10%
after SCIM-RT, versus 12% after 3D-CRT. Only three patients had grade 3
late rectal toxicity; all of them had undergone 3D-CRT. A multivariate
analysis of factors affecting grade 2-3 late rectal toxicity was
performed by use of the following: age (continuous), race (black vs
white), androgen deprivation (yes vs no), technique (SCIM-RT vs 3D-CRT),
grade 2-3 acute rectal toxicity (yes vs no), and volume of rectum
receiving the prescription dose (VrPr) (< or = 15 mL vs >15 mL). Only
the VrPr was a significant independent factor predicting grade 2-3 late
rectal toxicity. Only 15 SCIM-RT (7%) and 20 3D-CRT cases (20%) had a
VrPr > 15 mL. With SCIM-RT, the grade 2-3 late rectal toxicity rate at
18 months with a VrPr > 15 mL was 29%, versus 5% with a VrPr < or = 15
mL. With 3D-CRT, the grade 2-3 late rectal toxicity rate at 18 months
with a VrPr > 15 mL was 25%, versus 8% with a VrPr < or = 15 mL.
CONCLUSIONS: SCIM-RT, delivering 70.0 Gy at 2.5 Gy per fraction, had an
acute and late toxicity profile up to 18 months after therapy that was
similarto that of 3D-CRT delivering 78.0 Gy at 2.0 Gy per fraction. The
grade 2 actuarial combined rectal toxicity rate is low (10%) at 18
months, although it increased when rectal volumes > 15 mL received 70 Gy
with SCIM-RT. Only 7% of SCIM-RT cases received 70 Gy to > 15 ml of the
rectum. If longer follow-up confirms the low late toxicity rates,
SCIM-RT will be an alternative and more convenient method of
dose-escalation in the treatment of localized prostate cancer.
14
UI - 11464107
AU - Schmitz-Drager BJ; Eichholzer M; Beiche B; Ebert T
TI -
Nutrition and prostate cancer.
SO - Urol Int 2001;67(1):1-11
AD - Urology, EuromedClinic, Furth, Germany. bsd@euromed.de
Nutrition is apparently a major risk factor for the development and
progression of prostate cancer. Based on experimental studies and
epidemiologic data mainly from case-control studies or cohort studies,
there is strong evidence that reduction of the total energy consumption,
a diet comprising less than 30% fat, and increased intake of
phytoestrogens, vitamins D and E and selenium could yield a decreased
prostate cancer incidence. Furthermore, some of these measures appear to
have antitumoral capacity even in the presence of the disease. These
observations have provided a rationale to forward large prospective
trials on dietary interventions to prove the efficacy of the concept and
further delineate the correlation between nutritional compounds and
prostate cancer risk. These chemoprevention trials are either aiming a
reduction prostate cancer incidence or a decrease in tumor progression.
Depending on the study design, large numbers of individuals need to be
enrolled and long follow-up intervals are required thus making such
trials highly complex and cost-intensive. However, regarding the
potential relevance of chemoprevention on public health, further efforts
to identify nutritional factors affecting prostate cancer growth are
warranted.
15
UI - 11464109
AU - Altay B; Kefi A; Nazli O; Killi R; Semerci B; Akar I
TI -
Comparison of Gleason scores from sextant prostate biopsies and radical
prostatectomy specimens.
SO - Urol Int 2001;67(1):14-8
AD - Department of Urology, University of Ege Medical School, Izmir, Turkey.
baltay@mail.koc.net
OBJECTIVES: We compared the Gleason scores obtained from sextant
prostate biopsy and radical prostatectomy (RP) specimens in patients
with localized prostate cancer. PATIENTS AND METHODS: Sixty-one patients
having a clinical diagnosis of localized prostate cancer underwent
needle biopsy under transrectal ultrasonography (TRUS) and RP. Grading
and staging were assigned based on Gleason scores and the TNM system,
respectively. RESULTS: Mean patient age was 65.5 +/- 13.43 years and
mean PSA level was 14.69 +/- 3.95. Mean Gleason score for prostate
biopsy and RP specimen were 5.85 +/- 0.7 and 6.34 +/- 1.44,
respectively. With respect to clinical stage, there were 20 patients in
stage 1 and 41 patients in stage 2 prostate cancer. Comparing the
Gleason scores, the biopsy score was lower in 26 (42.26%) and higher
than RP specimens in 7 (11.84%) cases, and there was agreement between
the biopsy and RP specimens in 28 (45.9%) patients. The difference
between the two Gleason scores was +/- 1 for 18 patients (29.5%) and +/-
2 or more for 17 patients (27.86%). CONCLUSION: In our study, high
Gleason score biopsies with elevated PSA level (>10 ng/ml) were risk
factors for extraprostatic extension, and we demonstrated that Gleason
scores were significantly correlated with seminal vesicle and lymph node
invasion (p < 0.05). The Gleason scores of biopsy and RP specimens
agreed with 45.9% of TRUS-guided sextant prostate biopsies, and this
ratio was 91.1% in moderately differentiated tumors Copyright 2001 S.
Karger AG, Basel
16
UI - 11464110
AU - Stolzenburg JU; Pfeiffer H; Neuhaus J; Sommerfeld M; Dorschner W
TI -
Repair of inguinal hernias using the mesh technique during
extraperitoneal pelvic lymph node dissection.
SO - Urol Int 2001;67(1):19-23
AD - Department of Urology, University of Leipzig, Germany.
stolj@medizin.uni-leipzig.de
PURPOSE: This article describes our experience of using a totally
extraperitoneal approach for endoscopic pelvic lymphadenectomy and
inguinal hernia repair with the mesh technique in one procedure.
MATERIALS AND METHODS: A total of 52 patients underwent modified pelvic
lymph node dissection for the staging of prostate cancer. Eight of them
had hernia defects; 1 was recurrent. Five patients with direct and 3
patients with indirect inguinal hernias were treated by totally
extraperitoneal hernia repair with the placement of a mesh measuring at
least 10 x 15 cm (prolene mesh with incision and flap). RESULTS: The
mean duration of the lymphadenectomy itself was decreased from 150 min
(first 20 patients) to 70 min (n = 21-52). The mean additional procedure
time for hernioplasty was 15 min. The overall lymph node-positive rate
was 9.6%. The complication rate was 7.7%. Four patients developed
symptomatic lymphoceles, 1 of whom developed deep venous thrombosis. No
complications occurred which were attributed to hernia repair. Morbidity
did not rise, and hospitalization time did not increase for the patients
who underwent hernioplasty. There were no recurrences or neuralgias on
follow-up up to 2 years. CONCLUSIONS: By avoiding entry into the
peritoneal cavity, the extraperitoneal approach obviates intra-abdominal
complications (ileus, bowel injury, peritonitis) in both techniques. The
extraperitoneal approach for pelvic lymph node dissection allows
concomitant inguinal hernia to be repaired with low morbidity and within
an acceptable operating time. Copyright 2001 S. Karger AG, Basel
17
UI - 11603136
AU - Koh JS; Cheng CW; Foo KT
TI -
Spectrum of prostate cancer in the Singapore General Hospital (1980 to
1985).
SO - Ann Acad Med Singapore 2001 Sep;30(5):513-5
AD - Department of Urology, Singapore General Hospital, 1 Hospital Drive,
Singapore 169608.
INTRODUCTION: Serum prostate specific antigen (PSA) testing has
contributed to a dramatic rise in the incidence of prostate cancer
diagnosed in the last decade in the West as well as in Singapore. Now
prostate cancer is ranked as the sixth commonest cancer among men in
Singapore. To form the basis for comparisons and to assess the trends
and impact of these changes, we analysed the presentation, disease
characteristics and outcome of treatment of patients with prostate
cancer diagnosed in the pre-PSA era at the Singapore General Hospital
(SGH). MATERIALS AND METHODS: Of the 149 patients (1980 to 1985)
registered in the database, 134 (90%) records with full follow-up data
were available for the analysis. All patients were diagnosed and managed
at SGH. Follow-up and death data were collected through clinic visit,
phone interviews of the patients, relatives, family physicians and the
death registry. Survival analysis was carried out using the Kaplan-Meier
product limit method. RESULTS: The mean age at diagnosis was 69.8 years.
There were no significant changes with reference to each year during
1980 to 1985 and the mean number of diagnoses per year was 22.3. Of the
134 patients, 86% had either retention of urine or severe lower urinary
tract symptoms and 14% had metastatic disease at presentation. Most
histological diagnosis was made during prostatectomy; wherein 82% was
found with transurethral resection of the prostate (TURP) and 12% in
open prostatectomy, respectively. Pathological analysis during diagnosis
revealed that 72.4% patients had metastatic disease. Of which, 57.5% had
high-grade (Gleason > 7) tumours. Among these, 82% underwent TURP to
relieve urinary obstruction, while 26.1% received local irradiation to
the prostate. Majority had hormone therapy shortly after diagnosis in
the form of orchidectomy or oral diethylstilbestrol (76.1%). The median
crude survival (26 months) was minimal for metastatic patients.
CONCLUSION: The spectrum of prostate cancer in the pre-PSA era was
characterised by high stages of high-grade disease, with very limited
opportunity for successful treatment and hence survival.
18
UI - 10477007
AU - Gelblum DY; Potters L; Ashley R; Waldbaum R; Wang XH; Leibel S
TI -
Urinary morbidity following ultrasound-guided transperineal prostate
seed implantation.
SO - Int J Radiat Oncol Biol Phys 1999 Aug 1;45(1):59-67
AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center
at Mercy Medical Center, Rockville Centre, NY 11570, USA.
gelblumd@mskcc.org
PURPOSE: To assess the urinary morbidity experienced by patients
undergoing ultrasound-guided, permanent transperineal seed implantation
for adenocarcinoma of the prostate. METHODS AND MATERIALS: Between
with a diagnosis of clinically localized adenocarcinoma of the prostate,
and were treated with ultrasound-guided transperineal interstitial
permanent brachytherapy (TPIPB). Ninety-three patients are excluded from
this review, having received neoadjuvant antiandrogen therapy. TPIPB was
performed with 125I in 165 patients and with 103Pd in 435 patients.
Patients treated with implant alone received 160 Gy with 125I (pre TG43)
or 120 Gy with 103Pd. One hundred two patients received preimplant,
pelvic external beam radiation (XRT) to a dose of either 41.4 or 45 Gy
because of high-risk features including PSA > or = 10 and/or Gleason
score > or = 7. Combined modality patients received 120 Gy and 90 Gy,
respectively for 125I or 103Pd. All patients underwent postimplant
cystoscopy and placement of an indwelling Foley catheter for 24-48 h.
Follow-up was at 5 weeks after implant, every 3 months for the first 2
years, and then every 6 months for subsequent years. Patients completed
AUA urinary symptom scoring questionnaires at initial consultation and
at each follow-up visit. Urinary toxicity was classified by the RTOG
toxicity scale with the following adaptations; grade 1 urinary toxicity
was symptomatic nocturia or frequency requiring none or minimal medical
intervention such as phenazopyridine; grade 2 urinary toxicity was early
obstructive symptomatology requiring alpha-blocker therapy; and grade 3
toxicity was considered that requiring indwelling catheters or
posttreatment transurethral resection of the prostate for symptom
relief. Log-rank analysis and Chi-square testing was performed to assess
AUA score, prostate size, isotope selection, and the addition of XRT as
possible prognosticators of postimplant urinary toxicity. The prostate
volume receiving 150% of the prescribed dose (V150) was studied in
patients to assess its correlation with urinary toxicity. RESULTS:
Median follow-up was 37 months (range 6-68). Within the first 60 days,
37.3% of the patients reported grade 1 urinary toxicity, 41% had grade
2, and 2.2% had grade 3 urinary toxicity. By 6 months, 21.4% still
reported grade 1 urinary toxicity, whereas 12.8% and 3% complained of
grade 2 and 3 urinary difficulties, respectively. Patients with a
preimplant AUA score < or = 7 had significantly less grade II toxicity
at 60 days compared to those with an AUA score of >7 (32% vs. 59.2%,
respectively, p = 0.001). Similarly, prostatic volumes < or = 35 cc had
a significantly lower incidence of grade II urinary toxicity (p =
0.001). There was no difference in toxicity regarding the isotope used
(p = 0.138 at 60 days, p = 0.45 at 6 months) or the addition of
preimplant XRT (p = 0.069 at 60 days, p = 0.84 at 6 months).
Twenty-eight patients (4.7%) underwent TURP after 3 isotope half-lives
for protracted obstructive symptoms. Five of these men (17%) developed
stress incontinence following TURP, but all patients experienced relief
of their obstructive symptoms without morbidity at last follow-up. The
percent of the prostate receiving 150% of the prescribed dose (V150) did
not predict urinary toxicity. CONCLUSIONS: TPIPB is well tolerated but
associated with mild to moderate urinary morbidity. Pretreatment
prostatic volume and AUA scoring were shown to significantly predict for
grade 2 toxicity while the use of preimplant, pelvic XRT and isotope
selection did not. Patients undergoing TURP for protracted symptoms
following TPIPB did well with a 17% risk of developing stress
incontinence. V150 did not help identify patients at risk for urinary
morbidity. As transperineal prostate implantation is used more
frequently the associated toxicities and the definition of possible
pretreatment prognostic factors is necessary to
19
UI - 10487561
AU - Cha CM; Potters L; Ashley R; Freeman K; Wang XH; Waldbaum R; Leibel S
TI -
Isotope selection for patients undergoing prostate brachytherapy.
SO - Int J Radiat Oncol Biol Phys 1999 Sep 1;45(2):391-5
AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center
at Mercy Medical Center, Rockville Center, NY 11570, USA.
PURPOSE: Ultrasound-guided transperineal interstitial permanent prostate
brachytherapy (TIPPB) is generally performed with either 103Pd or 125I.
The use of 125I for low Gleason score tumors and 103Pd for higher
Gleason scores has been suggested based on isotope dose rate and cell
doubling time observed in in vitro studies. While many centers follow
these isotope selection criteria, other centers have elected to use only
a single isotope, regardless of Gleason score. No clinical data have
been published comparing these isotopes. This study was undertaken to
compare outcomes between 125I and 103Pd in a matched pair analysis for
patients undergoing prostate brachytherapy. METHODS AND MATERIALS: Six
hundred forty-eight consecutively treated patients with clinically
1997. Five hundred thirty-two patients underwent TIPPB alone, whereas
116 received pelvic external beam irradiation and TIPPB. Ninety-three
patients received androgen deprivation therapy prior to TIPPB. The
prescribed doses for TIPPB were 160 Gy for 125I (pre-TG43) and 120 Gy
for 103Pd. Patients treated with combination therapy received 41.4 or 45
Gy (1.8 Gy/fraction) external beam irradiation followed by a 3- to
5-week break and then received either a 120-Gy 125I or a 90-Gy 103Pd
after which the isotope selection was based on either Gleason score
(Gleason score 2-5:125I; Gleason 5-8:103Pd) or isotope availability. A
matched pair analysis was performed to assess any difference between
isotopes. Two hundred twenty-two patients were matched according to
Gleason score, prostate-specific antigen (PSA), and stage. PSA
relapse-free survival (PSA-RFS) was calculated based on the American
Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Group
definition of failure. Kaplan-Meier actuarial survival curves were
compared to assess differences in pretreatment PSA and Gleason score.
RESULTS: Univariate analysis of the 648 patients identified Gleason
score, pretreatment PSA value, and stage as significant factors to
predict PSA-RFS, but failed to identify isotope selection as
significant. To address the significance of isotope selection further,
the matched pair groupings were performed. The minimum follow-up for all
222 matched patients is 24 months with a median follow-up of 42 months
(24-82). The actuarial PSA-RFS at 5 years for all 222 patients is 86.5%.
One hundred eleven of the 222 matched patients received a 103Pd implant
with an 87.1% 5-year PSA-RFS. The remaining 111 patients underwent a
125I implant with an 85.9% 5-year PSA-RFS (p = n.s.). Analysis of
Gleason score subgroups 2-4, 5-6, and 7-9 failed to show any significant
difference in PSA-RFS comparing isotopes. Pretreatment PSA subgroups of
< or = 10 or > 10 ng/ml also failed to show any significant difference
in PSA-RFS survival comparing isotopes. Analysis of postimplant
dosimetry using dose delivered to 90% of the prostate volume (D90) did
not identify any difference between the isotope groups. CONCLUSIONS:
This matched pair analysis failed to demonstrate a difference for 125I
and 103Pd in PSA-RFS for patients undergoing TIPPB. In addition, there
were no observed advantages for either 125I or 103Pd in either the low
or high Gleason score groups. This data indicates that the role of
isotope selection for patients undergoing TIPPB requires further
clarification.
20
UI - 11265653
AU - Lee PC; Moran BJ
TI -
125 Gy or 135 Gy? Comments on the American Brachytherapy Society article
by Beyer et al. IJROBP 2000;47:273-275.
SO - Int J Radiat Oncol Biol Phys 2001 Mar 1;49(3):897-8
21
UI - 11265656
AU - Michalski JM; Williamson JF
TI -
In regard to Beyer, Nath, and Butler et al. IJROBP 2000;47:273-275.
SO - Int J Radiat Oncol Biol Phys 2001 Mar 1;49(3):900
22
UI - 11686937
AU - Miles BJ; Shalev M; Aguilar-Cordova E; Timme TL; Lee HM; Yang G; Adler
TI -
HL; Kernen K; Pramudji CK; Satoh T; Gdor Y; Ren C; Ayala G; Wheeler TM;
Butler EB; Kadmon D; Thompson TC
Prostate-specific antigen response and systemic T cell activation after
in situ gene therapy in prostate cancer patients failing radiotherapy.
SO - Hum Gene Ther 2001 Nov 1;12(16):1955-67
AD - Matsunaga-Conte Prostate Cancer Research Center, Scott Department of
Urology, Baylor College of Medicine, Houston, TX 77030, USA.
In an extended phase I/II study we evaluated 36 prostate cancer patients
with local recurrence after radiotherapy who received single or repeated
cycles of replication-deficient adenoviral vector (ADV)-mediated herpes
simplex virus-thymidine kinase (HSV-tk) plus ganciclovir (GCV) in situ
gene therapy with respect to serum PSA levels, alterations in immune
cells, and numbers of apoptotic cells in needle biopsies. An initial
cycle of HSV-tk plus GCV gene therapy caused a significant prolongation
of the mean serum PSA-doubling time (PSADT) from 15.9 to 42.5 months (p
= 0.0271) and in 28 of the injected patients (77.8%) there was a mean
PSA reduction (PSAR) of 28%. It took a mean of 8.5 months for the PSA to
return to the initial PSA (TR-PSA) value. A repeated cycle of gene
therapy failed to significantly extend PSADT but did result in
significant increases in PSAR (29.4%) and TR-PSA (10.5 months).
Moderately increased serum adenovirus antibody titers were generally
observed 2 weeks after initial vector injection. Also at this time there
was a statistically significant increase in the mean percent of CD8(+) T
cells positive for the HLA-DR marker of activation in peripheral blood
(p = 0.0088). Studies using prostate biopsies obtained at the same time
point demonstrated that vector DNA was detectable by PCR in most samples
yet all patients remained positive for prostate cancer in at least one
biopsy core. Further analysis demonstrated a correlation between the
level of CD8(+) cells and the number of apoptotic cells in biopsies
containing cancer cells (p = 0.042). We conclude that repeated cycles of
in situ HSV-tk plus GCV gene therapy can be administered to prostate
cancer patients who failed radiotherapy and have a localized recurrence.
Biological responses to this experimental therapy including increases in
PSADT, PSAR, and TR-PSA, and activated CD8(+) T cells present in the
peripheral blood, were demonstrated. Interestingly, the density of
CD8(+) cells in posttreatment biopsies correlated with the number of
apoptotic cells.
23
UI - 11795433
AU - Nelson WG; De Marzo AM; Deweese TL; Lin X; Brooks JD; Putzi MJ; Nelson
TI -
CP; Groopman JD; Kensler TW
Preneoplastic prostate lesions: an opportunity for prostate cancer
prevention.
SO - Ann N Y Acad Sci 2001 Dec;952():135-44
AD - The Johns Hopkins Comprehensive Cancer Center, Baltimore, Maryland
21231-1000, USA. bnelson@jhmi.edu
Environmental factors, especially the diet, play a prominent role in the
epidemic of prostate cancer (PCA), in the United States. Many candidate
dietary components have been proposed to influence human prostatic
carcinogenesis, including fat, calories, fruits and vegetables,
anti-oxidants, and various micronutrients, but the specific roles
dietary agents play in promoting or preventing PCA remain controversial.
We have collected evidence to suggest that GSTP1, the gene encoding the
pi-class glutathione S-transferase (GST), may serve a "caretaker"
function for prostatic cells. Although GSTP1 can be detected in normal
prostatic epithelium, in almost all PCA cases, PCA cells fail to express
GSTP1 polypeptides, and lack of GSTP1 expression most often appears to
be the result of somatic "CpG island" DNA methylation changes. Loss of
GSTP1 function also appears to be characteristic of prostatic epithelial
neoplasia (PIN) lesions, thought to represent PCA precursors. We have
recently learned that a new candidate early PCA precursor lesion,
proliferative inflammatory atrophy (PIA), characterized by proliferating
prostatic cells juxtaposed to inflammatory cells, contains epithelial
cells that express high levels of GSTP1. These findings have formed the
basis for a new model of prostatic carcinogenesis, in which prostatic
cells in PIA lesions, subjected to a barrage of inflammatory oxidants,
induce GSTP1 expression as a defense against oxidative genome damage.
When cells with defective GSTP1 genes appear amongst the PIA cells, such
cells become vulnerable to oxidants and electrophiles that inflict
genome damage that tends to promote neoplastic transformation to PIN and
PCA cells. Subsequently, PIN and PCA cells with defective GSTPI genes
remain vulnerable to similar stresses tending to promote malignant
progression. This new model for prostatic carcinogenesis has
implications for the design of new prostate cancer prevention
strategies. Rational prevention approaches might include: (i)
restoration of GSTPI expression via treatment with inhibitors of CpG
methylation, (ii) compensation for inadequate GSTPI activity via
treatment with inducers of general GST activity, and (iii) abrogation of
genome-damaging stresses via avoidance of exogenous carcinogens and/or
reduction of endogenous carcinogenic (particularly oxidant) stresses.
24
UI - 11795434
AU - Brawley OW; Barnes S; Parnes H
TI -
The future of prostate cancer prevention.
SO - Ann N Y Acad Sci 2001 Dec;952():145-52
AD - Office of the Director, National Cancer Institute, Bethesda, Maryland
20852, USA.
The dramatic international variation in prostate cancer mortality rates
suggest an environmental influence. This combined with a building
understanding of the genetic mechanisms of carcinogenesis encourages a
search for ways to prevent it. Androgenic stimulation over a period of
time has been suggested a cause of prostate cancer. The corollary to
this hypothesis is that lowering androgenic stimulation over time will
prevent prostate cancer. Decreasing androgenic stimulation of the
prostate with 5-alpha-reductase inhibitors such as finasteride has been
shown to decrease prostate size and may prevent prostate cancer. A
large, long-term clinical trial is underway using finasteride to
determine if it can prevent prostate cancer. Results are expected in
2004. Epidemiologic and laboratory studies also suggest that high
selenium and vitamin E intake lowers risk of prostate cancer. Recent
serendipitous findings of two randomized clinical trials support the
hypothesis that selenium and vitamin administration will decrease
prostate cancer risk. A study to assess these compounds is beginning.
Other promising, but less developed, interventions in chemoprevention of
prostate cancer include vitamin D supplementation and diet modification.
All will need to be rigorously evaluated before they can be advocated
for prostate cancer prevention.
25
UI - 11790276
AU - Errejon A; Crawford ED; Dayhoff J; O'Donnell C; Tewari A; Finkelstein J;
TI -
Gamito EJ
Use of artificial neural networks in prostate cancer.
SO - Mol Urol 2001 Winter;5(4):153-8
AD - ANNs in CaP Project, Denver, Colorado 80209, USA.
Artificial neural networks (ANNs) are a type of artificial intelligence
software inspired by biological neuronal systems that can be used for
nonlinear statistical modeling. In recent years, these applications have
played an increasing role in predictive and classification modeling in
medical research. We review the basic concepts behind ANNs and examine
the role of this technology in selected applications in prostate cancer
research.
26
UI - 11790277
AU - Porter C; O'Donnell C; Crawford ED; Gamito EJ; Errejon A; Genega E;
TI -
Sotelo T; Tewari A
Artificial neural network model to predict biochemical failure after
radical prostatectomy.
SO - Mol Urol 2001 Winter;5(4):159-62
AD - Department of Urology, Veterans Affairs Medical Center, Washington, DC,
USA.
BACKGROUND: Biochemical failure, defined here as a rise in the serum
prostate specific antigen (PSA) concentration to >0.3 ng/mL or the
initiation of adjuvant therapy, is thought to be an adverse prognostic
factor for men who undergo radical prostatectomy (RP) as definitive
treatment for clinically localized cancer of the prostate (CAP). We have
developed an artificial neural network (ANN) to predict biochemical
failure that may benefit clinicians and patients choosing among the
definitive treatment options for CAP. MATERIALS AND METHODS: Clinical
and pathologic data from 196 patients who had undergone RP at one
institution between 1988 and 1999 were utilized. Twenty-one records were
deleted because of missing outcome, Gleason sum, PSA, or clinical stage
data. The variables from the 175 remaining records were analyzed for
input variable selection using principal component analysis, decision
tree analysis, and stepped logistic regression. The selected variables
were age, PSA, primary and secondary Gleason grade, and Gleason sum. The
records were randomized and split into three bootstrap training and
validation sets of 140 records (80%) and 35 records (20%), respectively.
RESULTS: Forty-four percent of the patients suffered biochemical
failure. The average duration of follow up was 2.5 years (range 0-11.5
years). Forty-two percent of the patients had pathologic evidence of
non-organ-confined disease. The average area under the receiver operator
characteristic (ROC) curve for the validation sets was 0.75 +/- 0.07.
The ANN with the highest area under the ROC curve (0.80) was used for
prediction and had a sensitivity of 0.74, a specificity of 0.78, a
positive predictive value of 0.71, and a negative predictive value of
0.81. CONCLUSION: These results suggest that ANN models can predict PSA
failure using readily available preoperat
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