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NCI CANCERLIT® Search: Therapy of Prostate Cancer - September 2001

Imprima English

Ultima Vez Modificado: 1 de noviembre del 2001

Table of Contents

CancerMail from the National Cancer Institute

1
UI - 21198520
AU - Nagata C; Takatsuka N; Shimizu H; Hayashi H; Akamatsu T; Murase K
TI - Effect of soymilk consumption on serum estrogen and androgen concentrations in Japanese men.
SO - Cancer Epidemiol Biomarkers Prev 2001 Mar;10(3):179-84
AD - Department of Public Health, Gifu University School of Medicine, Japan.
Soy consumption has been associated with a reduced risk of prostate cancer. The mechanism for this association may involve the effect of soy on the endocrine system. We conducted a randomized dietary intervention study to determine the effects of soy consumption on serum levels of steroid hormones in men. Thirty-five men were randomly assigned to either a soymilk-supplemented group or a control group. The men in the soy-supplemented group were asked to consume 400 ml of soymilk daily for 8 weeks. The men in the control group maintained their usual diet. Blood samples were obtained just before the initiation of the dietary period and thereafter every two weeks for 12 weeks. Changes in hormone concentrations were analyzed and compared between the two groups using the mixed linear regression model against weeks from the start of the dietary period. The mean (SD) soymilk intake estimated from dietary records during the dietary study period was 342.9 (SD, 74.2) ml in the soymilk-supplemented group. There was a significant difference between the two groups in terms of changes in serum estrone concentrations, which tended to decrease in the soy-supplemented group and increase in the control group over time. None of the other hormones measured (estradiol, total and free-testosterone, or sex hormone-binding globulin) showed any statistical difference between the two groups in terms of patterns of change. The results of the study indicate that soymilk consumption may modify circulating estrone concentrations in men.

2
UI - 21234496
AU - Ruutu M; Mikkola A; Petas A
TI - Treatment of prostate cancer--any news?
SO - Ann Chir Gynaecol 2001;90(1):5-9
AD - Department of Urology, Helsinki University Central Hospital, Finland. mirja.ruutu@hus.fi

3
UI - 21243931
AU - Arango Toro O; Lorente Garin JA; Bielsa Gali O; Grino Garreta J; Gelabert Mas A
TI - [Anemia and neoadjuvant hormone therapy in radical surgery of localized cancer of the prostate]
SO - Actas Urol Esp 2001 Feb;25(2):105-9
AD - Servicio y Catedra de Urologia, Hospital del Mar, Universidad Autonoma de Barcelona, Barcelona.
RATIONALE: Erythropoiesis is stimulated by androgens either through a direct action on bone marrow cells or through increased erythropoietin production. Androgen deprivation is a known cause for anaemia. The aim of this study was to evaluate the effect of neoadjuvant hormone therapy prior to radical surgery on haemoglobin (Hb) and haematocrit (Ht) levels in localised prostate cancer. MATERIAL AND METHOD: 47 patients with clinical localised prostate cancer were given LH-RH analogs plus flutamide for complete androgenic blockade (CAB) for at least 3 months prior to radical prostatectomy. A blood profile was obtained prior to start CAB and 3 months after therapy, and peri-operative transfusional requirements were evaluated. To assess any significant changes. Student's t test was used in the statistical analysis of paired data. RESULTS: In our study all patients (100%) showed decreased Hb and Ht levels after 3 months on CAB. Mean decline for Hb was 1.9 g/dL (range 1.6-2.2) p:0.0001, and for Ht 5.8% (range 4.8-6.8) p:0.0001. Hb was lower than 12 g/dL in 10.6% patients after hormone therapy and anaemia results were normocytic-normochromic. 60% patients needed peri-operative blood transfusion, 2 units of packed cells on average. CONCLUSIONS: Neoadjuvant CAB prior to radical prostatectomy results in a significant decline of Hb and Ht levels after 3 months treatment. Such decline may contribute to increase peri-operative transfusional requirements in a group of patients undergoing aggressive surgery which in itself involves a significant blood loss.

4
UI - 21379544
AU - Vallancien G; Guillonneau B
TI - [Laparoscopic radical prostatectomy]
SO - Ann Chir 2001 Jul;126(6):505-7

5
UI - 21376174
AU - Smathers S; Wallner K; Sprouse J; True L
TI - Temporary PSA rises and repeat prostate biopsies after brachytherapy.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1207-11
AD - Department of Radiation Oncology, University of Washington, Seattle, Washington, USA.
PURPOSE: The long-standing confusion regarding the clinical relevance of postimplant biopsies is complicated by the common occurrence of temporary PSA rises between 1 and 2 years after brachytherapy. We report here 4 patients with temporary, self-limited PSA rises and postimplant biopsies, for whom radical prostatectomy was strongly advised but for whom surgery would probably have been the wrong choice. MATERIALS AND METHODS: Transperineal I-125 or Pd-103 implants were performed as previously described. After implantation, patients were followed routinely, with repeat PSA and physical examination at approximately every 4 to 6 months. Timing of postimplant PSAs was at the discretion of the patient and his doctors. Postimplant biopsies were performed in all cases out of concern for a persistently elevated serum PSA. Sections of fixed and embedded tissue were stained with standard hematoxylin and eosin. RESULTS: All 4 patients presented here were advised to have a salvage prostatectomy based primarily on their PSA changes. However, all of the patients have subsequently had a dramatic PSA fall, consistent with long-term cancer control, despite the fact that 3 of the 4 had histologic evidence of persistent cancer on repeat prostate biopsy. CONCLUSIONS: It is crucial that clinicians be aware of the potential for the doubly confusing situation of temporary PSA rises and apparently positive rebiopsies and the pressure it puts on both patients and their physicians to go ahead with inappropriate salvage therapy.

6
UI - 21376175
AU - Taylor JM; Griffith KA; Sandler HM
TI - Definitions of biochemical failure in prostate cancer following radiation therapy.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1212-9
AD - Department of Biostatistics, University of Michigan, Ann Arbor, MI 48104, USA. jmgt@umich.edu
PURPOSE: The American Society for Therapeutic Radiology and Oncology (ASTRO) published a consensus panel definition of biochemical failure following radiation therapy for prostate cancer. In this paper, we develop a series of alternative definitions of biochemical failure. Using data from 688 patients, we evaluated the sensitivity and specificity of the various definitions, with respect to a defined "clinically meaningful" outcome. METHODS AND MATERIALS: The ASTRO definition of biochemical failure requires 3 consecutive rises in prostate-specific antigen (PSA). We considered several modifications to the standard definition: to require PSA rises of a certain magnitude, to consider 2 instead of 3 rises, to require the final PSA value to be greater than a fixed cutoff level, and to define biochemical failure based on the slope of PSA over 1, 1.5, or 2 years. A clinically meaningful failure is defined as local recurrence, distant metastases, initiation of unplanned hormonal therapy, unplanned radical prostatectomy, or a PSA > 25 later than 6 months after radiation. RESULTS: Requiring the final PSA in a series of consecutive rises to be larger than 1.5 ng/mL increased the specificity of biochemical failure. For a fixed specificity, defining biochemical failure based on 2 consecutive rises, or the slope over the last year, could increase the sensitivity by up to approximately 20%, compared to the ASTRO definition. Using a rule based on the slope over the previous year or 2 rises leads to a slightly earlier detection of biochemical failure than does the ASTRO definition. Even with the best rule, only approximately 20% of true failures are biochemically detected more than 1 year before the clinically meaningful event time. CONCLUSION: There is potential for improvement in the ASTRO consensus definition of biochemical failure. Further research is needed, in studies with long follow-up times, to evaluate the relationship between various definitions of biochemical failure and true clinical outcome.

7
UI - 21376176
AU - Do T; Dave G; Parker R; Kagan AR
TI - Serum PSA evaluations during salvage radiotherapy for post-prostatectomy biochemical failures as prognosticators for treatment outcomes.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1220-5
AD - Department of Radiation Oncology, UCLA Medical Center, Los Angeles, CA, USA.
INTRODUCTION: Serum prostate specific antigen (PSA) levels have proved to be sensitive markers for the diagnosis of prostate cancer. In addition, PSA levels are useful for detecting and monitoring prostate cancer progression after radiotherapy. Serum PSA evaluations during radiotherapy, however, have not been well documented. In this study, we investigate the prognostic value of PSA evaluations during salvage radiotherapy for prostatectomy failures. METHODS: Forty-one patients with biochemical failures after prostatectomy treated with salvage radiotherapy consented to have their serum PSA levels evaluated at 30 Gy and 45 Gy of irradiation. All 41 patients had negative metastatic workup and pathologically uninvolved pelvic lymph nodes at the time of referral for salvage radiotherapy. Radiation therapy was delivered with 10--25 MV photons, with doses of 59.4--66.6 Gy. No patients received hormonal ablation therapy before irradiation. RESULTS: The mean follow-up for all patients was 30.9 months. At last follow-up, 28/41 patients (68.3%) were free from biochemical failure, with 20 of 41 patients (48.8%) expressing undetectable PSA levels. Serum PSA evaluations at 30 Gy did not significantly predict for either biochemical (p = 0.0917) or clinical (p = 0.106) disease-free outcome. However, serum PSA evaluations at 45 Gy significantly predicted for both biochemical (p = 0.0043) and clinical (p = 0.0244) disease-free outcomes, with PSA elevations at 45 Gy significantly associated with poor outcomes. On univariate analysis of prognosticators for biochemical failures, the following were significant: an elevation in serum PSA levels at 45 Gy, detectable serum PSA immediately after prostatectomy, Gleason score 7--10, and serum PSA level >1 ng/ml before salvage radiotherapy. CONCLUSION: Evaluation of serum PSA level at 45 Gy of salvage radiotherapy for biochemical relapses after prostatectomy may serve as a significant prognosticator for both biochemical and clinical disease-free outcomes.

8
UI - 21376177
AU - Martinez AA; Yan D; Lockman D; Brabbins D; Kota K; Sharpe M; Jaffray DA; Vicini F; Wong J
TI - Improvement in dose escalation using the process of adaptive radiotherapy combined with three-dimensional conformal or intensity-modulated beams for prostate cancer.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1226-34
AD - Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA. amartinez@beaumont.edu
PURPOSE: Advances in technology allow the creation of complex treatment plans with tightly conforming doses. However, variations in positioning of the organ/patient with respect to treatment beams necessitate the use of an appreciable margin, potentially limiting dose escalation in many patients. To (1) reduce this margin and (2) test the hypothesis that the achievable level of dose escalation is patient dependent, a patient-specific, confidence-limited planning target volume (cl-PTV) was constructed using an adaptive radiotherapy (ART) process for prostate cancer treatment developed in-house. The potential dose escalation achievable with this ART process is quantified for both conformal radiotherapy (CRT) delivery and intensity-modulated radiotherapy (IMRT) delivery. MATERIAL AND METHODS: Patients with organ confined prostate cancer were entered prospectively into an ART process developed in-house. This ART process has been designed to improve accuracy and precision of dose delivery, consequently enhancing dose escalation. In this process, a cl-PTV is constructed for each patient in the second week of treatment based upon on-line portal and CT images acquired during the first week of treatment. The treatment prescription dose, defined as the minimum dose to the cl-PTV, is selected based on predefined dose-volume constraints for rectum/bladder and derived from the pretreatment planning CT image. In addition, the treatment modality (CRT or IMRT) is determined based on the level of dose escalation achievable and the risk of inaccurate targeting. The potential for both dose escalation and the application of IMRT was evaluated by comparing the prescription doses delivered using the ART process, with the cl-PTV, to those in the traditional treatment process, with a conventional generic PTV. In addition, the distributions of potential geometric target underdosing and normal tissue overdosing were also calculated to evaluate the quality of the conventional treatment plans. RESULTS: One hundred and fifty patients have been treated with the ART process. When compared to the treatment dose delivered with the conventional treatment process (generic PTV), an average 5% (2.5--10%) more dose could be delivered using the ART process with CRT, and 7.5% (2.5--15%) more dose could be delivered with IMRT. Of the 150 patients, 70% were treated to a minimum cl-PTV dose > or = 77.4 Gy (81.3 Gy ICRU isocenter dose). Dosimetric analysis revealed that 81 Gy to the cl-PTV (or 86.7 Gy ICRU) could be prescribed to at least 50% of patients if IMRT was applied using the ART process. In contrast, IMRT did not yield an obvious dose escalation gain if patients were treated using the generic PTV. Our results also demonstrate that the cl-PTV is significantly smaller than the conventional generic PTV for most patients, with a mean volume reduction of 24% (range, 5--43%). CONCLUSION: These results support our hypothesis that the achievable level of dose escalation using ART is patient dependent. By using the ART process to develop a cl-PTV, one can (1) optimize the dose level, (2) increase the applicability of IMRT, and (3) improve the quality of dose delivery. The ART process provides the foundation to identify a suitable option (CRT or IMRT) for the delivery of a safe treatment and dose escalation. It is now our standard of practice for prostate cancer treatment.

9
UI - 21376178
AU - Potters L; Torre T; Fearn PA; Leibel SA; Kattan MW
TI - Potency after permanent prostate brachytherapy for localized prostate cancer.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1235-42
AD - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center at Mercy Medical Center, Rockville Center, NY 11570, USA. PottersL@mskcc.org
PURPOSE: The evaluation of potency preservation after treatment of localized prostate cancer with transperineal permanent prostate brachytherapy (PPB) and the efficacy of sildenafil were studied. METHODS AND MATERIALS: This study comprised 482 patients who were able to maintain an erection suitable for intercourse before treatment from a cohort of 1166 patients with clinically localized prostate cancer treated with PPB. All patients have been followed prospectively, and actuarial analysis was performed to assess potency preservation over time. Patients treated with sildenafil were evaluated as to its efficacy. RESULTS: The median follow-up of this cohort was 34 months (6--92), with a median age of 68 years (47--80). Potency was preserved in 311 of the 482 patients, with a 5-year actuarial potency rate of 52.7%. The 5-year actuarial potency rate for patients treated with PPB as monotherapy was 76%, and, for those treated with combination external beam radiotherapy (EBT) + PPB, 56% (p = 0.08). Patients treated with neoadjuvant androgen deprivation (NAAD) + PPB had a 5-year potency rate of 52%, whereas those with combination EBT + PPB + NAAD had a potency rate of 29% (p = 0.13). Cox regression analysis identified that pretreatment use of NAAD and patient age predicted for impotence (p = 0.0001 and 0.04, respectively). Of 84 patients treated with sildenafil, 52 had a successful outcome (62%). The response to sildenafil was significantly better in those patients not treated with NAAD (p = 0.04). CONCLUSIONS: The actuarial potency rates at 5 years for patients treated with PPB are lower than generally acknowledged, except for those patients treated with PPB as monotherapy. Patients who received sildenafil exhibited improved potency in a majority of cases.

10
UI - 21376179
AU - Pilepich MV; Winter K; John MJ; Mesic JB; Sause W; Rubin P; Lawton C; Machtay M; Grignon D
TI - Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1243-52
AD - Department of Radiation Oncology, Ann Arbor Regional CCOP, Ann Arbor, MI, USA. pilepicm@trinity-health.org
PURPOSE: To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival. METHODS AND MATERIALS: The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2--T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II. RESULTS: As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%, p = 0.004), biochemical disease-free survival = PSA <1.5 (24% vs. 10%, p < 0.0001), and cause-specific mortality (23% vs. 31%, p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2--6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%, p = 0.015). In patients with Gleason 7--10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival. CONCLUSION: In patients with Gleason score 2--6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.

11
UI - 21376180
AU - Merrick GS; Butler WM; Lief JH; Galbreath RW
TI - Five-year biochemical outcome after prostate brachytherapy for hormone-naive men < or = 62 years of age.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1253-7
AD - Schiffler Cancer Center, Wheeling Hospital, Wheeling, WV 26003-6300, USA. schifonc@wheelinghosp.com
PURPOSE: To evaluate 5-year biochemical disease-free outcome for hormone naive men 62 years of age or less who underwent transperineal ultrasound-guided permanent prostate brachytherapy. METHODS AND MATERIALS: 76 patients underwent transperineal ultrasound guided prostate brachytherapy using either (103)Pd or (125)I for clinical T1b--T2b NxM0 (1997 AJCC) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up, and no patient underwent pathologic lymph-node staging. 47 patients were implanted with either (103)Pd or (125)I monotherapy, and 29 patients received moderate-dose external-beam radiation therapy followed by a prostate brachytherapy boost. No patient received hormonal manipulation. The median patient age was 58 years (range, 48--62 years). The median follow-up was 37 months (range, 14--70 months). Follow-up was calculated from the day of implantation. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO) consensus definition. RESULTS: The actuarial 5-year biochemical disease-free survival rate was 98.7%. For patients with low-, intermediate-, and high-risk disease, 97.7%, 100%, and 100%, respectively, were free of biochemical failure. The median posttreatment prostate-specific antigen (PSA) for the entire group was 0.2 ng/mL. When stratified by risk group, the median posttreatment PSA was 0.2, 0.15, and 0.1 for patients with low-, intermediate-, and high-risk disease, respectively. CONCLUSION: With a median follow-up of 37 months, hormone naive patients < or = 62 years of age have a high probability of 5-year biochemical disease-free survival following permanent prostate brachytherapy with an apparent plateau on the PSA curve.

12
UI - 21388256
AU - Abdul M; Hoosein N
TI - Inhibition by anticonvulsants of prostate-specific antigen and interleukin-6 secretion by human prostate cancer cells.
SO - Anticancer Res 2001 May-Jun;21(3B):2045-8
AD - Rumbaugh-Goodwin Institute for Cancer Research, Plantation, Florida 33313, USA.
BACKGROUND: Anticonvulsants/antiepileptics inhibit high-frequency firing of action potentials that occur during an epileptic seizure, by mechanisms such as blocking sodium and calcium ion conductances. High sodium channel expression has been previously associated with aggressive behavior of prostate cancer (PCa) cell lines. The anticonvulsant phenytoin is known to inhibit the secretory activity and growth of human osteoblastic cells. MATERIALS AND METHODS: The effect of four anticonvulsants on the secretion of prostate-specific antigen (PSA) and interleukin-6 (IL-6) by human PCa cell lines (LNCaP, DU-145 and PC-3) was studied using immunoanalysis. RESULTS: Phenytoin and carbamazepine, which inactivate voltage-gated sodium channels, inhibited the secretion of PSA by LNCaP and IL-6 by DU-145 and PC-3 cell lines. Valproate and ethosuximide, which block calcium channels, had somewhat lower antisecretory effects. The growth of the three PCa cell lines in Matrigel was inhibited by all four anticonvulsants, at clinically-relevant doses. CONCLUSION: Further study of the usefulness of anticonvulsants in PCa therapy is warranted.

13
UI - 21379850
AU - Hammond LA; Van Krinks CH; Durham J; Tomkins SE; Burnett RD; Jones EL; Chandraratna RA; Brown G
TI - Antagonists of retinoic acid receptors (RARs) are potent growth inhibitors of prostate carcinoma cells.
SO - Br J Cancer 2001 Aug 3;85(3):453-62
AD - Division of Cancer Studies, University of Birmingham Medical School, Edgbaston, Birmingham, B15 2TT, UK.
Novel synthetic antagonists of retinoic acid receptors (RARs) have been developed. To avoid interference by serum retinoids when testing these compounds, we established serum-free grown sub-lines (>3 years) of the prostate carcinoma lines LNCaP, PC3 and DU145. A high affinity pan-RAR antagonist (AGN194310, K(d) for binding to RARs = 2-5 nM) inhibited colony formation (by 50%) by all three lines at 16-34 nM, and led to a transient accumulation of flask-cultured cells in G1 followed by apoptosis. AGN194310 is 12-22 fold more potent than all-trans retinoic acid (ATRA) against cell lines and also more potent in inhibiting the growth of primary prostate carcinoma cells. PC3 and DU145 cells do not express RARbeta, and an antagonist with predominant activity at RARbeta and RARgamma (AGN194431) inhibited colony formation at concentrations (approximately 100 nM) commensurate with a K(d)value of 70 nM at RARgamma. An RARalpha antagonist (AGN194301) was less potent (IC(50) approximately 200 nM), but was more active than specific agonists of RARalpha and of betagamma. A component(s) of serum and of LNCaP-conditioned medium diminishes the activity of antagonists: this factor is not the most likely candidates IGF-1 and EGF. In vitro studies of RAR antagonists together with data from RAR-null mice lead to the hypothesis that RARgamma-regulated gene transcription is necessary for the survival and maintenance of prostate epithelium. The increased potencies of RAR antagonists, as compared with agonists, suggest that antagonists may be useful in the treatment of prostate carcinoma. Copyright 2001 Cancer Research Campaign.

14
UI - 21416729
AU - Uchida T; Ohori M; Egawa S
TI - [Minimally invasive therapy for bladder and prostate cancer]
SO - Gan To Kagaku Ryoho 2001 Aug;28(8):1094-8
AD - Dept. of Urology, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Recently, minimally invasive therapy has been a key word in the medical field. Many new therapies have been developed in the field of urology. In this area, bacillus Calmette-Guerin (BCG) instillation therapy, transurethral resection of the bladder tumor and intra-arterial infusion with irradiation therapy are noted as minimally invasive therapies for bladder cancer. Laparoscopic prostatectomy, brachytherapy, three-dimensional conformal radiotherapy (3D-CRT) and high-intensity focused ultrasound (HIFU) have also been developed as minimally invasive therapies for prostate cancer. Though the establishment of the validity of each treatment will still take time, the best treatment for each patient should be chosen case by case, including considerations of postoperative quality of life and economic efficiency.

15
UI - 21237436
AU - Galbraith ME; Ramirez JM; Pedro LW
TI - Quality of life, health outcomes, and identity for patients with prostate cancer in five different treatment groups.
SO - Oncol Nurs Forum 2001 Apr;28(3):551-60
AD - School of Nursing, Loma Linda University, Loma Linda, CA, USA. mgalbraith@sn.llu.edu
PURPOSE/OBJECTIVES: To describe how different treatments for prostate cancer affect health-related quality of life (QOL), health status, and masculinity. DESIGN: Longitudinal survey design with descriptive, correlational, and comparative elements. SETTING: A tertiary medical center and associated clinics in a suburban community in the Southwestern United States. SAMPLE: 185 men with localized prostate cancer were enrolled from five treatment groups: watchful waiting (n = 30), surgery (n = 59), conventional radiation (n = 25), proton-beam radiation (n = 24), and a combination of conventional radiation and proton-beam radiation or mixed-beam radiation (n = 47). At six months, 163 remained on the study; at 12 months, 154 remained: and at 18 months, 153 remained. The average age was 68 years, and 82% of the men were white. METHODS: Men were enrolled at treatment and given a questionnaire with a self-addressed, stamped envelope for return. Questionnaires were mailed again at 6, 12, and 18 months. MAIN RESEARCH VARIABLES: Health-related QOL health status, prostate treatment-specific symptoms, and sex-role identity. FINDINGS: No overall difference in health-related QOL or health status was found, but post-hoc analysis revealed specific differences. The differences existed in sexual functioning and gastrointestinal treatment-specific symptoms. No relationship existed between masculinity and health-related QOL. CONCLUSIONS: Health-related QOL and health status are similar regardless of type of treatment. Radiation tends to produce more gastrointestinal symptoms, and surgery tends to produce more sexual functioning symptoms. Watchful waiting is associated with poorer general health. IMPLICATIONS FOR NURSING PRACTICE: Nurses can provide specific treatment-related information to men who are faced with making treatment decisions for prostate cancer and, in consultation with the health care team, can select a treatment best sulted to them.

16
UI - 21304139
AU - Koutrouvelis P; Lailas N; Hendricks F; Gil-Montero G; Sehn J; Katz S
TI - Three-dimensional computed tomography-guided monotherapeutic pararectal brachytherapy of prostate cancer with seminal vesicle invasion.
SO - Radiother Oncol 2001 Jul;60(1):31-5
AD - Uro-Radiology Prostate Institute, 8320 Old Courthouse Road #150, Vienna, Virginia 22182, USA.
PURPOSE: To treat patients with prostate cancer and seminal vesicle invasion with monotherapeutic three dimensional computed tomography (3-DCT)-guided posterior pararectal brachytherapy. METHODS AND MATERIALS: Three hundred and sixty two patients with clinical stage T1 a,b or T2 a,b of prostate cancer were referred for 3-DCT-guided brachytherapy. Each underwent ftirther staging with 3-D CT-guided pararectal biopsy of the seminal vesicles under local anesthesia during the pre-treatment CT-planning. Forty-three patients (12%) were upstaged to T3 cNoMo disease. In the set of 43 patients, Eight had Gleason's score< or =6, 24 Gleason's score=7, and 11 patients > or =8. Initial PSA was <10 ng/ml in 14 patients, 10-20 ng/ml in 11 patients, and >20 in 18 patients. Of the 43 patients, 37 patients were treated monotherapeutically with 3-D CT-guided brachytherapy. No patients received hormone therapy after the implant. The prescribed dosage to the seminal vesicles and prostate is 120 Gy with Pd-103 seeds and 144 Gy with 1-125 seeds. RESULTS: The prescribed dosage was achieved in all 37 patient's throughout the seminal vesicles whose range of target radiation extended 5-10 mm outside the target in the adjacent fat as calculated with post-implant CT-dosimetry with Varian Brachy Vision or MMS software. Prostate Specific Antigen (PSA) outcome data were available in 34 patients treated with monotherapy and follow up ranged from 12-56 months (median, 24 months). Decreased PSA levels were stratified into six groups based on the presenting Gleason's score and initial PSA. In the first group (with Gleason's score< or =6 and initial PSA <20 ng/ml), PSA levels decreased to less than 0.5 ng/ml in all seven patients (100%) after brachytherapy. In the second group (with Gleason's=7 and initial PSA<20 ng/ml), PSA levels decreased to less than 1 ng/ml in 11 of 13 patients (85%); additionally PSA levels decreased to less than 0.5 ng/ml in ten patients (77% in this group). In the third group (with Gleason's score=7 and initial PSA> 20 ng/ml), PSA decreased to less than 0.5 ng/ml in four out of eight patients (50%). All of the patients in the fourth group (with Gleason's score> or =8 and initial PSA<20 ng/ml) decreased their PSA levels to less than 0.5 ng/ml in three of three patients. PSA decreased less than 0.5 ng/ml in two out of three patients (67% in the last group with Gleason's score> or =8 and initial PSA> 20 ng/ml). There were no patients with Gleason's score of 1-6 and greater than 20 ng/ml initial PSA. Patients, irrespective of the Gleason's score and PSA, had an overall response of decreased PSA (less than 1 ng/ml) of 79%. CONCLUSION: 3-D CT-guided brachytherapy delivers adequate dosage to the seminal vesicles. Clinical and biochemical results are encouraging in patients with low initial PSA levels regardless of their Gleason's scores, but longer-term data in a greater number of patients is necessary.

17
UI - 21304140
AU - Perrin BA; Jordan TJ; Hounsell AR
TI - The design and evaluation of a phantom for the audit of the treatment chain for prostate radiotherapy.
SO - Radiother Oncol 2001 Jul;60(1):37-43
AD - North Western Medical Physics, Christie Hospital NHS Trust, Wilmslow Road, Withington, Manchester, M20 4BX, UK.
BACKGROUND AND PURPOSE: A phantom has been designed and built for a multi-institutional technique audit of the planning and delivery for radiotherapy to the prostate. The phantom was designed to test both the geometric and dosimetric accuracy of each aspect of the process. MATERIALS AND METHODS: The phantom consists of two curved water filled perspex tanks either side of a central block of solid water equivalent material. There are two options for the central section; a target defining block and a dose measurement block. The target defining block uses air holes to define a 3-D target volume for imaging via a CT scanner or a simulator. These holes can subsequently be filled with steel pins to allow megavoltage imaging. The dose measurement block allows thimble chamber measurements to be made at pre-selected points in a 5x5mm array. Five dose measurement points, typical for a prostate planning target volume (PTV) were selected. Initial evaluation of the phantom was performed by auditing the prostate radiotherapy planning and treatment chain at one institution. RESULTS: Agreement between the phantom and planned geometry confirmed that the stages of image acquisition, transfer and manipulation were accurately performed. Agreement within 0.5% was found between phantom and water tank measurements for dose calibration at a reference point. The measured dose delivered was within 2% of the dose calculated by the planning computer for all of the selected measurement points. The target volume marked by the steel pins was visible using electronic portal imaging. CONCLUSIONS: The phantom is a useful tool for the technique audit of prostate radiotherapy.

18
UI - 21336978
AU - Mueller-Lisse UG; Swanson MG; Vigneron DB; Hricak H; Bessette A; Males RG; Wood PJ; Noworolski S; Nelson SJ; Barken I; Carroll PR; Kurhanewicz J
TI - Time-dependent effects of hormone-deprivation therapy on prostate metabolism as detected by combined magnetic resonance imaging and 3D magnetic resonance spectroscopic imaging.
SO - Magn Reson Med 2001 Jul;46(1):49-57
AD - Magnetic Resonance Science Center, Department of Radiology, University of California-San Francisco, 1 Irving Street, San Francisco, CA 94143-1290, USA.
Combined MRI and 3D spectroscopic imaging (MRI/3D-MRSI) was used to study the metabolic effects of hormone-deprivation therapy in 65 prostate cancer patients, who underwent either short, intermediate, or long-term therapy, compared to 30 untreated control patients. There was a significant time-dependent loss of the prostatic metabolites choline, creatine, citrate, and polyamines during hormone-deprivation therapy, resulting in the complete loss of all observable metabolites (total metabolic atrophy) in 25% of patients on long-term therapy. The amount and time-course of metabolite loss during therapy significantly differed for healthy and malignant tissues. Citrate levels decreased faster than choline and creatine levels during therapy, resulting in an increase in the mean (choline + creatine)/citrate ratio with duration of therapy. Due to a loss of all MRSI detectable citrate, this ratio could not be used to identify cancer in 69% of patients on long-term therapy. In the absence of citrate, however, residual prostate cancer could still be detected by elevated choline levels (choline/creatine ratio > or =1.5), or the presence of only choline in the proton spectrum. The loss of citrate and the presence of total metabolic atrophy correlated roughly with decreasing serum prostatic specific antigen levels with increasing therapy. In summary, MRI/3D-MRSI provided both a measure of residual cancer and a time-course of metabolic response following hormone-deprivation therapy. Magn Reson Med 46:49-57, 2001. Copyright 2001 Wiley-Liss, Inc.

19
UI - 21340751
AU - Jackson A
TI - Partial irradiation of the rectum.
SO - Semin Radiat Oncol 2001 Jul;11(3):215-23
AD - Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA.
Data gathered from dose escalation protocols for the treatment of prostate cancers conducted in the past 10 years have shown that rectal toxicity can be controlled by the use of careful conformal techniques. The most severe complications of rectal irradiation (obstruction and fistula requiring colostomy) have been essentially eliminated. The most frequent gastrointestinal complications of conformal radiotherapy of prostate cancer are now rectal bleeding associated with telangiectatic changes to the vasculature of the submucosa, and in severe cases, ulceration requiring cautery procedures and or transfusion. The benefits of 3-dimensional conformal radiotherapy (3D-CRT) are strongly technique dependent, with a strong dose response for single techniques for prescription doses over 70 Gy. Studies of rectal motion show that the anterior wall can move approximately 1 cm during treatment, so portions of the anterior rectal wall will regularly receive the full prescription dose if posterior margin sizes >/= 1 cm are used in designing the planning target volume (PTV). There is strong evidence that increased rectal shielding and posterior PTV margin sizes approximately 0.6 cm reduce rectal complication rates. Despite uncertainties due to rectal motion, studies of dose-volume histograms (DVHs) show that rectal toxicity is strongly influenced by the percent volumes of rectal wall exposed to doses approximately 70 Gy and higher. Recent data suggests that percent volumes of rectal wall exposed doses between 40 to 50 Gy, and the existence of a reserve of unexposed tissue may also play a role in determining rectal bleeding rates. Copyright 2001 by W.B. Saunders Company

20
UI - 21371755
AU - Parr C; Davies G; Nakamura T; Matsumoto K; Mason MD; Jiang WG
TI - The HGF/SF-induced phosphorylation of paxillin, matrix adhesion, and invasion of prostate cancer cells were suppressed by NK4, an HGF/SF variant.
SO - Biochem Biophys Res Commun 2001 Aug 3;285(5):1330-7
AD - Department of Surgery, Department of Oncology, University of Wales College of Medicine, Heath Park, Cardiff, CF14-4XN, United Kingdom. parrc@cardiff.ac.uk
Hepatocyte growth factor/scatter factor (HGF/SF) plays a crucial role in cancer cell migration, matrix adhesion, invasion, and angiogenesis, via the phosphorylation of the c-met tyrosine kinase. This study examined the ability of NK4, a recently discovered HGF/SF variant, to inhibit the influence of HGF/SF on cell-matrix interaction, paxillin phosphorylation, and invasion of prostate cancer cells. HGF/SF was shown to dramatically enhance tumour cell motility, invasion, cell-matrix adhesion, together with an increase in the degree of paxillin phosphorylation and formation of focal adhesion complexes. However, these HGF/SF-induced effects were suppressed by the presence of NK4. NK4 effectively inhibited the degree of HGF/SF-induced paxillin phosphorylation and matrix adhesion. As a consequence, the matrix invasion of these prostate cancer cells was also suppressed by NK4. In conclusion, this study shows that these HGF/SF-enhanced events, which are critical steps in metastasis, can be inhibited through the addition of NK4, thus warranting further in vivo studies on the implication of NK4 as a potential antimetastasis agent in prostate cancer. Copyright 2001 Academic Press.

21
UI - 21402385
AU - Kalapurakal JA; Mittal BB; Sathiaseelan V
TI - Re-irradiation and external hyperthermia in locally advanced, radiation recurrent, hormone refractory prostate cancer: a preliminary report.
SO - Br J Radiol 2001 Aug;74(884):745-51
AD - Division of Radiation Oncology, Robert H Lurie Comprehensive Cancer Center, Northwestern Memorial Hospital, 251 East Huron Street, Galter Pavilion LC-178, Chicago, IL 60611, USA.
The purpose of this report is to present the preliminary results of re-irradiation and external hyperthermia in patients with locally advanced, previously irradiated, hormone refractory prostate cancer. Three consecutive patients with symptomatic, locally advanced, previously irradiated and hormone refractory prostate cancer were treated with further irradiation (30.6-50 Gy) and external hyperthermia (5-8 treatments). All patients had complete resolution of symptoms lasting for 12-24 months. Significant tumour shrinkage, including complete tumour response, was demonstrated by CT and endoscopy. In one case, at 2 years after re-treatment, there is continued tumour regression and bone regeneration in the pelvis. Two patients had local control of tumour, which continued until most recent follow-up at 12 months and more than 24 months, respectively. Another case developed local recurrence at 17 months. At most recent follow-up, no patient has experienced significant treatment-related side effects. In these patients with no other therapeutic alternatives, re-irradiation and hyperthermia can provide durable tumour response for more than a year, resulting in significant improvement in quality of life. Further clinical studies are warranted.

22
UI - 21413539
AU - Pinski J; Parikh A; Bova GS; Isaacs JT
TI - Therapeutic implications of enhanced G(0)/G(1) checkpoint control induced by coculture of prostate cancer cells with osteoblasts.
SO - Cancer Res 2001 Sep 1;61(17):6372-6
AD - Johns Hopkins Oncology Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA.
Osteoblastic metastases are common in lethal prostate cancer. Effective therapy for bone metastases is lacking. Thus, developing an appropriate in vitro screening system is critical to prioritize which of the newly developed agents should undergo additional expensive and time-consuming in vivo evaluation in bone metastases animal models. In the past, such in vitro screening evaluated the response of prostate cancer cells to chemotherapeutic agents in monoculture without the presence of osteoblasts. In such monoculture, prostate cancer cells have a high (i.e., >90%) proliferative growth fraction. In contrast, the growth fraction (i.e., mean: 7.1 +/- 0.8%; median: 3.1%) in 117 metastatic sites of prostate cancer obtained from 11 androgen ablation failing patients at "warm" autopsy was found to be >10-fold lower. To better mimic the lower growth fraction observed clinically, LNCaP human prostate cancer cells were cocultured with membrane-separated hFOB human osteoblasts. Such coculturing significantly lowered the growth fraction of the LNCaP cells (i.e., from >90 to <30%) without enhancing their low rate (i.e., <5%) of apoptosis. This lowering of the growth fraction was documented using flow cytometry, Ki-67 immunohistochemistry, and 5-bromo-2-deoxyuridine incorporation. Using RNase protection assays, it was documented that coculture with osteoblasts causes enhanced p53, p27, and p21 expression leading to a decrease in the number of LNCaP cells entering the cell cycle (i.e., enhanced number of LNCaP cells in G(0)-G(1) and a decrease in S and G(2)-M and thus the growth fraction). This osteoblast-induced enhanced G(0)-G(1) checkpoint control affected the chemosensitivity of LNCaP cells. This was documented by coculturing LNCaP cells with hFOB cells to condition the medium for 3 days to lower the growth fraction to <30% before exposing the LNCaP cells for 48 h to various concentrations of Taxol, doxorubicin, or thapsigargin (TG). In standard high (i.e., >90%) growth fraction cultures (i.e., cultures in the absence of osteoblast-conditioned medium), there was a dose-dependent and significant (P < 0.05) increase in apoptosis of LNCaP cells exposed to Taxol or doxorubicin. In contrast, even the highest dose of Taxol (1 microM) did not enhance apoptosis of lower growth fraction LNCaP cells cultured in osteoblast-conditioned medium. Similarly, only the highest concentration of doxorubicin (1 microM) enhanced apoptosis in lower growth fraction cells. In contrast, 100 nM TG induced high levels of apoptosis in both lower and high-growth fraction LNCaP cultures. These results demonstrate that the osteoblast/LNCaP coculture system is a better in vitro screen than monoculture to identify proliferation-independent agents for the treatment of prostate cancer bone metastases, and TG is such an agent.

23
UI - 20488076
AU - Olson KB; Pienta KJ
TI - Use of bisphosphonates in the treatment of prostate cancer.
SO - Oncology (Huntingt) 2000 Sep;14(9):1361-4; discussion 1364-7
AD - University of Michigan, Comprehensive Cancer Center, USA.

24
UI - 21239583
AU - Small EJ
TI - Docetaxel in prostate cancer.
SO - Anticancer Drugs 2001 Feb;12 Suppl 1():S17-20
AD - Urologic Oncology Program, UCSF Comprehensive Cancer Center, 1600 Divisadero St., 3rd Floor, San Francisco, CA 94115, USA. smalle@medicine.ucsf.edu
In contrast to several other tumor types, there has been relatively little experience with docetaxel in hormone-refractory prostate cancer. However, two phase II trials investigated the combination of docetaxel with estramustine, and reported prostate-specific antigen response rates of 69 and 74% and objective responses in 23% and 57% of patients. This activity is comparable with that of other estramustine combinations. However, there is uncertainty about whether estramustine itself should be omitted from therapy because of its emetogenic and thromboembolic potential, and also over the optimal schedule of docetaxel to avoid neutropenia. Preliminary data suggest that weekly docetaxel, with or without limited exposure to estramustine, may provide the right balance between efficacy and tolerability. Phase III studies now in progress are comparing regimens containing docetaxel and estramustine with a recent standard therapy consisting of mitoxantrone plus prednisone. In the future, the efficacy of docetaxel plus estramustine may be enhanced by adding agents to this regimen.

25
UI - 21367164
AU - Buchler EF
TI - [Prostate cancer: prevention and patient education--wishes and demands from the viewpoint of patients]
SO - Wien Med Wochenschr 2001;151(9-10):206-7
AD - Selbsthilfe Prostatakrebs, Medizinisches Selbsthilfezentrum, Obere Augartenstrasse 26-28, A-1020 Wien. ekkehard.buechler@newsclub.at
Everyone is personally responsible for his/her yearly medical checks. But who is responsible for the fact that everybody knows about them? Prostate cancer is the most common malicious illness of men in Austria. How good are the chances to detect prostate cancer by various means of examinations? With the cost of one man whose cancer has been detected too late you can do the PSA test for about 10,000 men.

26
UI - 21381626
AU - Kucuk O; Sarkar FH; Sakr W; Djuric Z; Pollak MN; Khachik F; Li YW; Banerjee M; Grignon D; Bertram JS; Crissman JD; Pontes EJ; Wood DP Jr
TI - Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy.
SO - Cancer Epidemiol Biomarkers Prev 2001 Aug;10(8):861-8
AD - Division of Hematology and Oncology, Wayne State University, and Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA. kucuko@karmanos.org
An inverse association has been observed between dietary intake of lycopene and the risk of prostate cancer. We investigated the effects of lycopene supplementation in patients with prostate cancer. Twenty-six men with newly diagnosed, clinically localized (14 T(1) and 12 T(2)) prostate cancer were randomly assigned to receive 15 mg of lycopene (n = 15) twice daily or no supplementation (n = 11) for 3 weeks before radical prostatectomy. Biomarkers of differentiation and apoptosis were assessed by Western blot analysis on benign and malignant parts of the prostate gland. Prostatectomy specimens were entirely embedded, step-sectioned, and evaluated for pathological stage, Gleason score, volume of cancer, and extent of high-grade prostatic intraepithelial neoplasia. Plasma levels of lycopene, insulin-like growth factor-1 (IGF-1), IGF binding protein-3, and prostate-specific antigen were measured at baseline and after 3 weeks of supplementation or observation. Eleven (73%) subjects in the intervention group and two (18%) subjects in the control group had no involvement of surgical margins and/or extra-prostatic tissues with cancer (P = 0.02). Twelve (84%) subjects in the lycopene group and five (45%) subjects in the control group had tumors <4 ml in size (P = 0.22). Diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia was present in 10 (67%) subjects in the intervention group and in 11 (100%) subjects in the control group (P = 0.05). Plasma prostate-specific antigen levels decreased by 18% in the intervention group, whereas they increased by 14% in the control group (P = 0.25). Expression of connexin 43 in cancerous prostate tissue was 0.63 +/- 0.19 absorbance in the lycopene group compared with 0.25 +/- 0.08 in the control group (P = 0.13). Expression of bcl-2 and bax did not differ significantly between the two study groups. IGF-1 levels decreased in both groups (P = 0.0002 and P = 0.0003, respectively). The results suggest that lycopene supplementation may decrease the growth of prostate cancer. However, no firm conclusions can be drawn at this time because of the small sample size.

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