National Cancer Institute®
Last Modified: August 1, 2002
UI - 2029421
AU - Varenhorst E; Pedersen KV; Carlsson P; Berglund K; Lofman O
TI - Screening for carcinoma of the prostate in a randomly selected population using duplicate digital rectal examination.
SO - Acta Oncol 1991;30(2):273-5
AD - Department of Urology Norrkoping, Sweden.
Of 9,026 males, aged 50-69 years, 1,494 were randomly selected and invited to participate in a screening programme for carcinoma of the prostate. Of these 1,163 (78%) accepted. Rectal examination was performed independently by a general practitioner (GP) and by a urologist at the GP's surgery. Carcinoma of the prostate was suspected by one or both physicians in 45 cases, and subsequently confirmed by cytological investigation in 13 cases. Ten patients underwent radical prostatectomy, one received radiation treatment, one case was too advanced for curative treatment, and one was scheduled for subsequent reassessment. Screening, as a means of early diagnosis of carcinoma of the prostate by either a urologist or a GP, using digital rectal examination, thus appears to be a cost-effective procedure, though the question still remains whether this will lead to prolongation of survival or not.
UI - 12115487
AU - Suzuki K; Koike H; Matsui H; Ono Y; Hasumi M; Nakazato H; Okugi H;
TI - Sekine Y; Oki K; Ito K; Yamamoto T; Fukabori Y; Kurokawa K; Yamanaka H Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3.
SO - Int J Cancer 2002 Jun 20;99(6):846-52
AD - Department of Urology, Gunma University School of Medicine, Maebashi, Japan. email@example.com
Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells. Copyright 2002 Wiley-Liss, Inc.
UI - 12109135
AU - Norris JS; Hyer ML; Voelkel-Johnson C; Lowe SL; Rubinchik S; Dong JY
TI - The use of Fas Ligand, TRAIL and Bax in gene therapy of prostate cancer.
SO - Curr Gene Ther 2001 May;1(1):123-36
AD - Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, South Carolina 29425, USA. firstname.lastname@example.org
Prostate cancer is the second leading cause of cancer death in the United States. Treatment options for confined disease are generally successful in prolonging life but long-term cures (10-15 years) are elusive for the majority of patients. The prognosis for advanced extra-capsular prostate cancer is grim. However, we are now entering the era of gene therapy options for treatment of prostate cancer. The human genome project coupled with genomics and protemics are providing information that will lead to selection of genes for treatment of prostate cancer. The problem is the science of delivery lags behind knowledge of gene function. Thus, it is important to develop therapies that do not require delivery to 100% of tumor cells but which nevertheless kills the entire cancer by virtue of the bystander effect or other means. This review covers the use, in gene therapy, of apoptotic inducing molecules such as Fas Ligand, and TRAIL which are believed to induce bystander killing activity and Bax which also may function in a similar way.
UI - 12118020
AU - Papandreou CN; Daliani DD; Thall PF; Tu SM; Wang X; Reyes A; Troncoso P;
TI - Logothetis CJ Results of a phase II study with doxorubicin, etoposide, and cisplatin in patients with fully characterized small-cell carcinoma of the prostate.
SO - J Clin Oncol 2002 Jul 15;20(14):3072-80
AD - Department of Genitourinary Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. email@example.com
PURPOSE: To determine the activity and toxicity of doxorubicin in combination with cisplatin and etoposide in patients with small-cell prostate carcinoma (SCPCa) and to characterize the clinicopathologic features of SCPCa. PATIENTS AND METHODS: Patients with SCPCa (pure or mixed), measurable disease, good organ function, and no prior treatment with doxorubicin, etoposide, or cisplatin were treated every 4 weeks with doxorubicin 50 mg/m(2) as a 24-hour intravenous (IV) infusion followed by etoposide 120 mg/m(2)/d and cisplatin 25 mg/m(2)/d IV on days 2 to 4. RESULTS: Thirty-eight patients (36 assessable for response) were treated for a median of four cycles. Twenty-nine (81%) of 36 patients had prior hormonal therapy. Study patients had visceral metastases, lytic bone disease, and relatively low serum prostate-specific antigen (PSA). We observed 22 partial responses (response rate, 61% in an intent-to-treat analysis); toxicity was severe (grade 3 or 4 neutropenia 100%, thrombocytopenia 66%, mucositis 21%, and infection 68%). Three patients died of toxicity. Median time to progression and overall survival time were 5.8 months and 10.5 months, respectively. Performance status, serum albumin, and number of organs involved (but not PSA, carcinoembryonic antigen, or neuroendocrine markers) were predictors of survival. CONCLUSION: SCPCa presents unique clinicopathologic features. Addition of doxorubicin to the etoposide/cisplatin regimen caused higher toxicity in this patient population and failed to improve outcome. Given these results, we do not recommend further development of this regimen for patients with SCPCa. Improvement in therapy will come from understanding the biology of SCPCa progression and integrating new targeted therapies into the treatment of SCPCa.
UI - 12124817
AU - Moul JW
TI - Radical prostatectomy versus radiation therapy for clinically localized prostate carcinoma: the butcher and the baker selling their wares.
SO - Cancer 2002 Jul 15;95(2):211-4
UI - 12124826
AU - D'Amico AV; Saegaert T; Chen MH; Renshaw AA; George D; Oh W; Kantoff PW
TI - Initial decline in hemoglobin during neoadjuvant hormonal therapy predicts for early prostate specific antigen failure following radiation and hormonal therapy for patients with intermediate and high-risk prostate cancer.
SO - Cancer 2002 Jul 15;95(2):275-80
AD - Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. firstname.lastname@example.org
BACKGROUND: Declines in serum hemoglobin (Hgb) levels occur from the use of androgen suppression therapy (AST) in the treatment of prostate cancer patients. We studied whether time to prostate specific antigen (PSA) failure following external beam radiation therapy (RT) and AST could be predicted by the rate of decline in the Hgb level following the administration of neoadjuvant AST or by the Hgb level at presentation or at the start of RT. METHODS: The study cohort comprised 110 intermediate or high-risk prostate cancer patients who were managed using three-dimensional conformal RT (70 Gy) and 6 months of AST (2 months neoadjuvant, concurrent, and adjuvant). A Cox regression multivariable analysis was performed to evaluate the ability of the rate of decline of the Hgb from baseline to the start of RT, baseline PSA level, Gleason score, percent positive biopsies, and T-category to predict time to PSA failure. RESULTS: A decline in the Hgb level of 1 g/dL or more during the first month of AST was the only significant predictor of time to PSA failure (P = 0.02) on multivariable analysis. The relative risk of PSA failure (95% confidence interval) for patients with a decline in Hgb level during the first month (> or = 1 g/dL vs. < 1 g/dL) was 6.3 (2.4, 8.3) and the 3-year estimate of PSA outcome was 66% versus 82% (P = 0.04), respectively. There were no imbalances in the pretreatment prognostic factors or length of follow-up in each of these groups. CONCLUSION: A decline of 1 g/dL or more in Hgb level during the first month of neoadjuvant AST was a predictor of early PSA failure following RT and AST in intermediate and high-risk prostate cancer patients. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10673
UI - 12124827
AU - D'Amico AV; Whittington R; Malkowicz SB; Cote K; Loffredo M; Schultz D;
TI - Chen MH; Tomaszewski JE; Renshaw AA; Wein A; Richie JP Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era.
SO - Cancer 2002 Jul 15;95(2):281-6
AD - Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA. email@example.com
BACKGROUND: To the authors' knowledge, consensus is lacking regarding the relative long-term efficacy of radical prostatectomy (RP) versus conventional-dose external beam radiation therapy (RT) in the treatment of patients with clinically localized prostate carcinoma. METHODS: A retrospective cohort study of 2635 men treated with RP (n = 2254) or conventional-dose RT (n = 381) between 1988-2000 was performed. The primary endpoint was prostate specific antigen (PSA) survival stratified by treatment received and high-risk, intermediate-risk, or low-risk group based on the serum PSA level, biopsy Gleason score, 1992 American Joint Commission on Cancer clinical tumor category, and percent positive prostate biopsies. RESULTS: Estimates of 8-year PSA survival (95% confidence interval [95% CI]) for low-risk patients (T1c,T2a, a PSA level < or = 10 ng/mL, and a Gleason score < or = 6) were 88% (95% CI, 85, 90) versus 78% (95% CI, 72, 83) for RP versus patients treated with RT, respectively. Eight-year estimates of PSA survival also favored RP for intermediate-risk patients (T2b or Gleason score 7 or a PSA level > 10 and < or = 20 ng/mL) with < 34% positive prostate biopsies, being 79% (95% CI, 73, 85) versus 65% (95% CI, 58, 72), respectively. Estimates of PSA survival in high-risk (T2c or PSA level > 20 ng/mL or Gleason score > or = 8) and intermediate-risk patients with at least 34% positive prostate biopsies initially favored RT, but were not significantly different after 8 years. CONCLUSIONS: Intermediate-risk and low-risk patients with a low biopsy tumor volume who were treated with RP appeared to fare significantly better compared with patients who were treated using conventional-dose RT. Intermediate-risk and high-risk patients with a high biopsy tumor volume who were treated with RP or RT had long-term estimates of PSA survival that were not found to be significantly different. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10657
UI - 12124828
AU - Fowler FJ Jr; McNaughton Collins M; Walker Corkery E; Elliott DB; Barry
TI - MJ The impact of androgen deprivation on quality of life after radical prostatectomy for prostate carcinoma.
SO - Cancer 2002 Jul 15;95(2):287-95
AD - Center for Survey Research, University of Massachusetts, Boston, Massachusetts, USA. firstname.lastname@example.org
BACKGROUND: Androgen deprivation is commonly prescribed for men with a rising prostate specific antigen level after radical prostatectomy, despite scant evidence regarding its efficacy and side effects. In the current study, the authors compared measures of health-related quality of life (HRQOL) in men who were treated with androgen deprivation after radical prostatectomy with those for men who underwent surgery but were not treated with androgen deprivation. METHODS: Medicare Provider and Analysis and Review (MedPAR) files were used to identify men who had undergone radical prostatectomies between 1991-1992. Medicare Part B data then were used to select two samples: men who subsequently were androgen deprived and those who were not. In 1999, a mail survey was administered that addressed a range of disease-related and treatment-related issues, including HRQOL. Age-adjusted comparisons of responses to seven multiitem measures of HRQOL were performed. RESULTS: The overall response rate was 82%. On all seven HRQOL measures (impact of cancer and treatment, concern regarding body image, mental health, general health, activity, worries about cancer and dying, and energy), there were statistically significant decrements associated with androgen deprivation. CONCLUSIONS: Patients and physicians must weigh the price patients pay with regard to HRQOL against the uncertain benefits of early androgen deprivation. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10656
UI - 12124837
AU - Samson DJ; Seidenfeld J; Schmitt B; Hasselblad V; Albertsen PC; Bennett
TI - CL; Wilt TJ; Aronson N Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma.
SO - Cancer 2002 Jul 15;95(2):361-76
AD - Technology Evaluation Center, Blue Cross and Blue Shield Association, Washington, DC 20005, USA. email@example.com
BACKGROUND: The current systematic review and meta-analysis compared monotherapy and combined androgen blockade in the treatment of men with advanced prostate carcinoma. Outcomes of interest included overall, cancer specific, and progression-free survival; time to treatment failure; adverse events; and quality of life. METHODS: The literature search identified randomized trials comparing monotherapy (orchiectomy and luteinizing hormone-releasing hormone [LHRH] agonists) with combination therapy using orchiectomy or a LHRH agonist plus a nonsteroidal or steroidal antiandrogen. Dual independent review occurred. The meta-analysis used a random effects model. RESULTS: Twenty-one trials compared survival after monotherapy with survival after combined androgen blockade (n = 6871 patients). The meta-analysis found no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade and those treated with monotherapy (20 trials; hazard ratio [HR] = 0.970; 95% confidence interval [95% CI], 0.866-1.087). The authors determined a statistically significant difference in survival at 5 years that favored combined androgen blockade (10 trials; HR = 0.871; 95% CI, 0.805-0.942). For the subgroup of patients with a good prognosis, there was no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. To the authors' knowledge there is little evidence published to date comparing the effects of combined androgen blockade and monotherapy on quality of life, but the single randomized trial that adequately addressed this outcome reported an advantage for monotherapy over combined androgen blockade. CONCLUSIONS: A thorough examination of the usefulness of combined androgen blockade must balance the modest increase in expected survival observed at 5 years against the increased risk of adverse effects and the potential for adversely affecting the patient's overall quality of life. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10647
UI - 11842739
AU - Wachter S; Gerstner N; Mock U; Potter R
TI - Planning target volume and dose prescription in definitive radiotherapy for prostate cancer with favourable prognostic factors.
SO - Front Radiat Ther Oncol 2002;36():1-9
AD - Department of Radiotherapy and Radiobiology, University Hospital, Vienna, Austria. firstname.lastname@example.org
UI - 11842740
AU - Sandler HM
TI - Dose escalation for prostate cancer: which dose for which person?
SO - Front Radiat Ther Oncol 2002;36():10-5
AD - Department of Radiation Oncology, University of Michigan, Ann Arbor, Mich., USA. email@example.com
UI - 11842746
AU - Maurer U; Eble MJ
TI - The technique of 125I permanent implants.
SO - Front Radiat Ther Oncol 2002;36():159-65
AD - Universitatsklinikum der RWTH Aachen, Klinik fur Strahlentherapie, Aachen, Deutschland.
UI - 11842747
AU - Vordermark D; Flentje M
TI - Planning target volume definition in dose-escalation studies.
SO - Front Radiat Ther Oncol 2002;36():16-24
AD - Klinik und Poliklinik fur Strahlentherapie, Wurzburg, Germany. firstname.lastname@example.org
UI - 11842748
AU - Maurer U; Wiegel T; Hinkelbein W; Eble MJ
TI - Interstitial brachytherapy with permanent seed implants in early prostate cancer.
SO - Front Radiat Ther Oncol 2002;36():166-70
AD - Kliniken fur Strahlentherapie, Universitatsklinikum der RWTH, Aachen, Deutschland.
Excellent clinical results after permanent seed implantation have been reported by various centers in large cohorts of patients. However, all of these had extensive experience in this special field of radiotherapy and the therepy and the follow-up time is too short for definite conclusions. The fact that this option of treatment can be carried out on an outpatient basis and that it allows to get the patient back to normal as far as social environment and work are concerned, has led to wide acceptance of this particular mode of therapy. Therefore, permanent seed implantation is a possible treatment option for localized prostate cancer and can be offered to patients with T1- T2a tumors, PSA levels of < 10 and a Gleason score of < 7. By using permanent seed implantation in these selected patients, it seems possible to achieve results comparable with surgery alone or percutaneous, 3D-planned radiotherapy.
UI - 11842749
AU - Deger S; Bohmer D; Roigas J; Turk I; Budach V; Loening SA
TI - Interstitial hyperthermia using thermoseeds in combination with conformal radiotherapy for localized prostate cancer.
SO - Front Radiat Ther Oncol 2002;36():171-6
AD - Department of Urology, Charite Hospital, Humboldt University, Berlin, Germany. email@example.com
UI - 11842750
AU - Bohmer D; Deger S; Dinges S; Schnorr D; Loening SA; Budach V
TI - High-dose rate brachytherapy--the Charite experience.
SO - Front Radiat Ther Oncol 2002;36():177-82
AD - Department of Radiotherapy, Charite, Humboldt University of Berlin, Germany. firstname.lastname@example.org
UI - 11842751
AU - Galalae R; Kovacs G; Loch T; Bertermann H; Kohr P; Oldorp A; Kimmig B
TI - Anatomy-related and transrectal sonography-guided interstitial high-dose rate brachytherapy combined with elective irradiation of the pelvic lymphatics for localized prostate cancer: the Kiel experience.
SO - Front Radiat Ther Oncol 2002;36():183-90
AD - Interdisciplinary Brachytherapy Center, Christian Albrechts University, Kiel, Germany. email@example.com
UI - 11842752
AU - Debus J; Zierhut D; Didinger B; Schlegel W; Wannenmacher M
TI - Inverse planning and intensity-modulated radiotherapy in patients with prostate cancer.
SO - Front Radiat Ther Oncol 2002;36():25-34
AD - Radiologische Klinik, Universitatsklinikum Heidelberg, Deutsches Krebsforschungszentrum (dkfz), Heidelberg, Deutschland. firstname.lastname@example.org
Inverse planning and IMRT are methods with the potential to improve substantially clinical results in radiotherapy of prostate cancer. Available early clinical data demonstrate the feasibility and safety of high-dose IMRT for patients with localized prostate cancer and provide a proof-of-principle that this method improves dose conformality relative to tumor coverage and exposure to normal tissues.
UI - 11842753
AU - Wiegel T; Hinkelbein W
TI - Radiotherapy after radical prostatectomy in patients with prostate-specific antigen elevation.
SO - Front Radiat Ther Oncol 2002;36():35-42
AD - Department of Radiotherapy, University Hospital Benjamin Franklin, Freie Universitat, Berlin, Germany. email@example.com
UI - 11842754
AU - Eble MJ; Maurer U
TI - Is radiotherapy of pelvic lymph nodes successful in prostate cancer?
SO - Front Radiat Ther Oncol 2002;36():43-8
AD - Department of Radiotherapy, University Hospital, Aachen, Germany. firstname.lastname@example.org
UI - 11842755
AU - Forster TH; Stoffel F; Gasser TC
TI - Hormone therapy in advanced prostate cancer.
SO - Front Radiat Ther Oncol 2002;36():49-65
AD - Urologic Clinic, University of Basel, Switzerland.
UI - 11842757
AU - Heicappell R
TI - Controversies in chemotherapy of prostate cancer.
SO - Front Radiat Ther Oncol 2002;36():72-80
AD - Department of Urology, Universitatsklinikum Benjamin Franklin, Freie Universitat, Berlin, Germany. email@example.com
UI - 11842758
AU - Bolla M; de Reijke TM; Zurlo A; Collette L
TI - Adjuvant hormone therapy in locally advanced and localized prostate cancer: three EORTC trials.
SO - Front Radiat Ther Oncol 2002;36():81-6
AD - EORTC Radiotherapy and Genito-Urinary Cooperative Groups, EORTC Data Center, Brussels, Belgium. MBolla@chu-grenoble.fr
UI - 11842760
AU - Kirschner-Hermanns R; Jakse G
TI - Quality of life following radical prostatectomy.
SO - Front Radiat Ther Oncol 2002;36():99-105
AD - Urological Clinic, University Clinic, Rheinisch-Westfalische Technical University, Aachen, Germany.
UI - 12095577
AU - Levitt SH; Khan FM
TI - In regard to Purdy JA, Michalski JM. Does the evidence support the enthusiasm over 3D conformal radiation therapy and dose escalation in the treatment of prostate cancer? Int J Radiat Oncol Biol Phys 2001;51:867-870.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):1085; discussion 1085-6
UI - 12095581
AU - Aronowitz J; Schwartz J; Moran MJ
TI - In regard to Sherertz et al., IJROBP 2001; 51:1241-1245.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):1087; discussion 1088
UI - 12095555
AU - Lieberfarb ME; Schultz D; Whittington R; Malkowicz B; Tomaszewski JE;
TI - Weinstein M; Wein A; Richie JP; D'Amico AV Using PSA, biopsy Gleason score, clinical stage, and the percentage of positive biopsies to identify optimal candidates for prostate-only radiation therapy.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):898-903
AD - Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA 02215, USA. firstname.lastname@example.org
PURPOSE: An identification of prostate cancer patients most likely to benefit from prostate-only radiation was made based upon the pretreatment prostate-specific antigen (PSA), biopsy Gleason score, clinical stage, percentage of positive biopsies, and the 5-year postoperative PSA outcome. METHODS: Between 1989 and 2000, 2099 patients underwent radical prostatectomy for clinically localized prostate cancer. The primary end points were pathologic evidence of seminal vesicle invasion 2(SVI), extracapsular extension (ECE) with or without positive surgical margins, and the 5-year postoperative PSA outcome. RESULTS: Pretreatment PSA, biopsy Gleason score, and clinical stage were used to assign patients to low-, intermediate-, and high-risk groups. These risk groups were stratified by the percentage of positive biopsies and the primary pathologic and biochemical outcomes examined. The rates of SVI, ECE with positive margin, and no biochemical evidence of disease (bNED) for low-risk patients with < or =50% positive biopsies were 2%, 7%, and 93%, respectively. Patients with >50% positive biopsies had higher rates of SVI and ECE (5% and 11%, respectively) and 52% bNED (p < 0.0001). For intermediate-risk patients with < or =17% positive biopsies, the rates of SVI, ECE with positive margin, and bNED were 3%, 9%, and 90%, respectively. As the percentage of positive biopsies increased above 17% in intermediate-risk patients, there was a statistically significant increase in SVI and ECE and a significant decrease in bNED. CONCLUSIONS: Low-risk patients with < or =50% positive biopsies and intermediate-risk patients with < or =17% positive biopsies had a very low risk of SVI and ECE with positive surgical margins. Given that the presence of SVI and ECE with positive surgical margins was uncommon (<10%) with a > or =90% PSA failure-free survival after radical prostatectomy, these patients may be optimal candidates for radiation therapy directed at the prostate only (prostate gland + 1.5-cm margin).
UI - 12095556
AU - Kupelian PA; Reddy CA; Carlson TP; Altsman KA; Willoughby TR
TI - Preliminary observations on biochemical relapse-free survival rates after short-course intensity-modulated radiotherapy (70 Gy at 2.5 Gy/fraction) for localized prostate cancer.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):904-12
AD - Department of Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH 44195, USA. email@example.com
PURPOSE: To compare the preliminary biochemical relapse-free survival rates 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. METHODS AND treated with SCIM-RT and 116 with 3D-CRT. The SCIM-RT cases were treated to 70 Gy (2.5 Gy/fraction) using 5 intensity-modulated fields using a dynamic multileaf collimator. The BAT transabdominal ultrasound system was used for localization of the prostate gland in all SCIM-RT cases. The 116 3D-CRT cases were treated to 78.0 Gy (2.0 Gy/fraction). The study sample therefore comprised 282 cases; 70 Gy in 28 fractions is equivalent to 78 Gy in 39 fractions for late-reacting tissues, according to the linear-quadratic model. The median follow-up for all cases was 25 months (range 3-42). The median follow-up was 21 months for the SCIM-RT cases (range 3-31) and 32 months for the 3D-CRT cases (range 3-42). The follow-up period was shorter for the SCIM-RT cases, because SCIM-RT was consecutive rising prostate-specific antigen levels after reaching a nadir. The analysis was then repeated with a more stringent definition of biochemical control: reaching and maintaining a prostate-specific antigen level of < or =0.5 ng/mL. Radiation Therapy Oncology Group toxicity scores were used to assess complications. RESULTS: For the 282 patients, the biochemical relapse-free survival rate at 30 months was 91% (95% confidence interval 88-95%). The biochemical relapse-free survival rate at 30 months for 3D-CRT vs. SCIM-RT was 88% (95% confidence interval 82-94%) vs. 94% (95% confidence interval 91-98%), respectively. The difference was not statistically significant between the two treatment arms (p = 0.084). The multivariate time-to-failure analysis using the Cox proportional hazards model for clinical parameters showed the pretreatment prostate-specific antigen level (p <0.001) and biopsy Gleason score (p <0.001) to be the only independent predictors of biochemical relapse. Clinical T stage (p = 0.66), age (p = 0.15), race (p = 0.25), and neoadjuvant androgen deprivation (p = 0.66) were not independent predictors of biochemical failure. SCIM-RT showed only a trend toward a better outcome on multivariate analysis (p = 0.058). Late rectal toxicity was limited; the actuarial combined Grade 2 and 3 late rectal toxicity rate at 30 months was 5% for SCIM-RT vs. 12% for 3D-CRT (p = 0.24). Grade 3 late rectal toxicity (rectal bleeding requiring cauterization) occurred in a total of 10 patients. The actuarial Grade 3 late rectal toxicity rate at 30 months was 2% for the SCIM-RT cases and 8% for the 3D-CRT cases (p = 0.059). Late urinary toxicity was rare in both groups. CONCLUSION: With the currently available follow-up period (< or =30 months), the hypofractionated intensity-modulated radiotherapy schedule of 70.0 Gy delivered at 2.5 Gy/fraction had a comparable biochemical relapse profile with the prior 3D-CRT schedule delivering 78.0 at 2.0 Gy/fraction. The late rectal toxicity profile has been extremely favorable. If longer follow-up confirms the favorable biochemical failure and low late toxicity rates, SCIM-RT will be an alternative and more convenient way of providing dose escalation in the treatment of localized prostate cancer.
UI - 12095557
AU - Hurwitz MD; Kaplan ID; Hansen JL; Prokopios-Davos S; Topulos GP; Wishnow
TI - K; Manola J; Bornstein BA; Hynynen K Association of rectal toxicity with thermal dose parameters in treatment of locally advanced prostate cancer with radiation and hyperthermia.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):913-8
AD - Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. firstname.lastname@example.org
PURPOSE: Although hyperthermia has been used for more than two decades in the treatment of pelvic tumors, little is known about the potential impact of heat on rectal toxicity when combined with other treatment modalities. Because rectal toxicity is a concern with radiation and may be exacerbated by hyperthermia, definition of the association of thermal dose parameters with rectal toxicity is important. In this report, we correlate rectal toxicity with thermal dose parameters for patients treated with hyperthermia and radiation for prostate cancer. METHODS AND MATERIALS: Thirty patients with T2b-T3b disease (1992 American Joint Committee On Cancer criteria) enrolled in a Phase II study of external beam radiation +/- androgen-suppressive therapy with two transrectal ultrasound hyperthermia treatments were assessed for rectal toxicity. Prostatic and anterior rectal wall temperatures were monitored for all treatments. Rectal wall temperatures were limited to 40 degrees C in 19 patients, 41 degrees C in 3 patients, and 42 degrees C in 8 patients. Logistic regression was used to estimate the log hazard of developing National Cancer Institute Common Toxicity Criteria Grade 2 toxicity based on temperature parameters. The following were calculated: hazard ratios, 95% confidence intervals, p values for statistical significance of each parameter, and proportion of variability explained for each parameter. RESULTS: Gastrointestinal toxicity was limited to Grade 2. The rate of acute Grade 2 proctitis was greater for patients with an allowable rectal wall temperature of >40 degrees C. In this group, 7 of 11 patients experienced acute Grade 2 proctitis, as opposed to 3 of 19 patients in the group with rectal wall temperatures limited to 40 degrees C (p = 0.004). Preliminary assessment of long-term toxicity revealed no differences in toxicity. Hazard ratios for acute Grade 2 proctitis for allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax were 9.33 (p = 0.01), 3.66 (p = 0.03), and 2.29 (p = 0.08), respectively. A model combining these three parameters explained 48.6% of the variability among groups. CONCLUSION: Rectal toxicity correlates with maximum allowable rectal wall temperature, average rectal wall Tmax, and average prostate Tmax for patients undergoing transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer. Further definition of this association of thermal dose parameters with rectal toxicity in treatment of pelvic malignancies with hyperthermia should advance the goal of delivering thermal therapy in an effective yet safe manner.
UI - 12095558
AU - Hovdenak N; Wang J; Sung CC; Kelly T; Fajardo LF; Hauer-Jensen M
TI - Clinical significance of increased gelatinolytic activity in the rectal mucosa during external beam radiation therapy of prostate cancer.
SO - Int J Radiat Oncol Biol Phys 2002 Jul 15;53(4):919-27
AD - Department of Oncology, Bergen University Hospital, Bergen, Norway.
PURPOSE: Rectal toxicity (proctitis) is a dose-limiting factor in pelvic radiation therapy. Mucosal atrophy, i.e., net extracellular matrix degradation, is a prominent feature of radiation proctitis, but the underlying mechanisms are not known. We prospectively examined changes in matrix metalloproteinase (MMP)-2 and MMP-9 (gelatinase A and B) in the rectal mucosa during radiation therapy of prostate cancer, as well as the relationships of these changes with symptomatic, structural, and cellular evidence of radiation proctitis. METHODS AND MATERIALS: Seventeen patients scheduled for external beam radiation therapy for prostate cancer were prospectively enrolled. Symptoms of gastrointestinal toxicity were recorded, and endoscopy with biopsy of the rectal mucosa was performed before radiation therapy, as well as 2 and 6 weeks into the treatment course. Radiation proctitis was assessed by endoscopic scoring, quantitative histology, and quantitative immunohistochemistry. MMP-2 and MMP-9 were localized immunohistochemically, and activities were determined by gelatin zymography. RESULTS: Symptoms, endoscopic scores, histologic injury, and mucosal macrophages and neutrophils increased from baseline to 2 weeks. Symptoms increased further from 2 weeks to 6 weeks, whereas endoscopic and cellular evidence of proctitis did not. Compared to pretreatment values, there was increased total gelatinolytic activity of MMP-2 and MMP-9 at 2 weeks (p = 0.02 and p = 0.004, respectively) and 6 weeks (p = 0.006 and p = 0.001, respectively). Active MMP-2 was increased at both time points (p = 0.0001 and p = 0.002). Increased MMP-9 and MMP-2 at 6 weeks was associated with radiation-induced diarrhea (p = 0.007 and p = 0.02, respectively) and with mucosal neutrophil infiltration (rho = 0.62). CONCLUSIONS: Pelvic radiation therapy causes increased MMP-2 and MMP-9 activity in the rectal mucosa. These changes correlate with radiation-induced diarrhea and granulocyte infiltration and may contribute to abnormal connective tissue remodeling in radiation proctitis.
UI - 12137810
AU - Chodak GW; Keane T; Klotz L; Hormone Therapy Study Group
TI - Critical evaluation of hormonal therapy for carcinoma of the prostate.
SO - Urology 2002 Aug;60(2):201-8
AD - Midwest Prostate and Urology Health Center, Chicago, Illinois 60640, USA.
UI - 12137823
AU - Krahn MD; Bremner KE; Asaria J; Alibhai SM; Nam R; Tomlinson G; Jewett
TI - MA; Warde P; Naglie G The ten-year rule revisited: accuracy of clinicians' estimates of life expectancy in patients with localized prostate cancer.
SO - Urology 2002 Aug;60(2):258-63
AD - Department of Medicine, University of Toronto School of Medicine, Toronto, Ontario, Canada.
OBJECTIVES: To determine the accuracy of clinicians' predictions of life expectancy in patients with localized prostate cancer, when provided with information about age and comorbidity, and to determine whether life expectancy estimates predict the choice of initial treatment. METHODS: A survey was sent by facsimile to 191 Canadian urologists and radiation oncologists asking them to estimate the life expectancy and choose the initial therapy (radical prostatectomy, radiation, or watchful waiting) for 18 patient scenarios: two prostate cancer scenarios, each with three ages and three levels of comorbidi