HIGH DOSE RADIATION DELIVERED BY INTENSITY MODULATED CONFORMAL RADIOTHERAPY IMPROVES THE OUTCOME OF LOCALIZED PROSTATE CANCER

Abstract

No AccessJournal of UrologyCLINICAL UROLOGY: Original Articles1 Sep 2001HIGH DOSE RADIATION DELIVERED BY INTENSITY MODULATED CONFORMAL RADIOTHERAPY IMPROVES THE OUTCOME OF LOCALIZED PROSTATE CANCERis corrected byOUTCOME OF LOCALIZED PROSTATE CANCER MICHAEL J. ZELEFSKY, ZVI FUKS, MARGIE HUNT, HENRY J. LEE, DANNA LOMBARDI, CLIFTON C. LING, VICTOR E. REUTER, E.S. VENKATRAMAN, and STEVEN A. LEIBEL MICHAEL J. ZELEFSKYMICHAEL J. ZELEFSKY , ZVI FUKSZVI FUKS , MARGIE HUNTMARGIE HUNT , HENRY J. LEEHENRY J. LEE , DANNA LOMBARDIDANNA LOMBARDI , CLIFTON C. LINGCLIFTON C. LING , VICTOR E. REUTERVICTOR E. REUTER , E.S. VENKATRAMANE.S. VENKATRAMAN , and STEVEN A. LEIBELSTEVEN A. LEIBEL View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)65855-7AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized prostate cancer. Materials and Methods: Between October 1988 and December 1998, 1,100 patients with clinical stages T1c-T3 prostate cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. Results: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] ± 4), 58% (95% CI ± 6) and 38% (95% CI ± 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI ± 8) compared to 90% (95% CI ± 8) for those treated with 75.6 to 86.4 Gy. (p = 0.05). The corresponding rates were 50% (95% CI ± 8) versus 70% (95% CI ± 6) in intermediate risk cases (p = 0.001), and 21% (95% CI ± 8) versus 47% (95% CI ± 6) in unfavorable risk cases (p = 0.002). Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI ± 2) compared with 5% (95% CI ± 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI ± 2) compared with 14% (95% CI ± 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. Conclusions: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio. References 1 : Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis. JAMA1999; 281: 1598. Google Scholar 2 : The prognostic significance of post-irradiation biopsy results in patients with prostatic cancer. J Urol1986; 135: 510. Link, Google Scholar 3 : Extended biopsy followup after full course radiation for resectable prostatic carcinoma. J Urol1975; 113: 371. Link, Google Scholar 4 : Routine prostate biopsies following radiotherapy for prostate cancer: results for 226 patients. Urology1995; 45: 624. Google Scholar 5 : Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer. Int J Radiat Oncol Biol Phys1997; 37: 247. Google Scholar 6 : The effect of dose on local control of prostate cancer. Int J Radiat Oncol Biol Phys1988; 15: 1299. Google Scholar 7 : External beam radiotherapy dose-response of prostate cancer. Int J Radiat Oncol Biol Phys1997; 39: 1011. Google Scholar 8 : Late radiation damage in prostate cancer patients treated by high dose external radiotherapy in relation to rectal dose. Int J Radiat Oncol Biol Phys1990; 18: 23. Google Scholar 9 : The biological basis and clinical application of three-dimensional conformal external beam radiation therapy in carcinoma of the prostate. Semin Oncol1994; 21: 580. Google Scholar 10 : Three-dimensional conformal radiotherapy and dose escalation: where do we stand?. Semin Radiat Oncol1998; 8: 107. Google Scholar 11 : The feasibility of dose escalation with three-dimensional conformal radiotherapy in patients with prostatic carcinoma. Cancer J Sci Am1995; 1: 42. Google Scholar 12 : Long term tolerance of high dose three dimensional conformal radiotherapy in patients with localized prostate cancer. Cancer1999; 85: 2460. Google Scholar 13 : Three-dimensional conformal radiation therapy in localized carcinoma of the prostate: Interim report of a phase I dose-escalation study. J Urol, part 21994; 152: 1792. Abstract, Google Scholar 14 : Dose escalation with three dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys1998; 41: 491. Google Scholar 15 : Locally advanced prostatic cancer: long-term toxicity after three-dimensional conformal radiation therapy—a dose-escalation study. Radiology1998; 209: 169. Google Scholar 16 : Prostate. In: American Joint Committee on Cancer. Cancer Staging Manual. Philadelphia: Lippincott-Raven1997: 181. Google Scholar 17 : Histologic grading and clinical staging of prostatic carcinoma. In: Urologic Pathology: The Prostate. Edited by . Philadelphia: Lea & Febiger1977: 171. Chapt. 9. Google Scholar 18 : Conformal radiation treatment of prostate cancer using inversely planned intensity-modulated photon beams produced with dynamic multileaf collimation. Int J Radiat Oncol Biol Phys1996; 35: 721. Google Scholar 19 : Planning, delivery, and quality assurance of intensity-modulated radiotherapy using dynamic multileaf collimator: a strategy for large-scale implementation for the treatment of carcinoma of the prostate. Int J Radiat Oncol Biol Phys1997; 39: 863. Google Scholar 20 : Clinical experience with intensity modulated radiation therapy (IMRT) in prostate cancer. Radiother Oncol2000; 55: 241. Google Scholar 21 : Neoadjuvant hormonal therapy improves the therapeutic ratio in patients with bulky prostatic cancer treated with three-dimensional conformal radiation therapy. Int J Radiat Oncol Biol Phys1994; 29: 755. Google Scholar 22 : Neoadjuvant androgen ablation prior to radiotherapy for prostate cancer: reducing the potential morbidity of therapy. Urology1997; 49: 38. Google Scholar 24 Consensus statement: guidelines for PSA following radiation therapy. American Society for Therapeutic Radiology and Oncology Consensus Panel. Int J Radiat Oncol Biol Phys1997; 37: 1035. Google Scholar 25 : Evaluation of radiation effect, tumor differentiation and prostate specific antigen staining in sequential prostate biopsies after external beam radiotherapy for patients with prostate carcinoma. Cancer1997; 79: 81. Google Scholar 26 : Histopathologic effects of three dimensional conformal external beam radiation therapy on benign and malignant prostate tissues. Am J Surg Pathol1999; 23: 1021. Google Scholar 27 : Nonparametric estimation from incomplete observations. J Am Stat Assoc1958; 53: 457. Google Scholar 28 : Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Reports1966; 50: 163. Google Scholar 29 : Regression models and life tables. J R Stat Soc1972; 34: 187. series B. Google Scholar 30 : External beam radiotherapy versus radical prostatectomy for clinical stage T1–2 prostate cancer: therapeutic implications of stratification by pretreatment PSA levels and biopsy Gleason scores. Cancer J Sci Am1997; 3: 78. Google Scholar 31 : Equivalent biochemical failure-free survival after external beam radiation therapy or radical prostatectomy in patients with a pretreatment prostate specific antigen of >4–20 ng/ml. Int J Radiat Oncol Biol Phys1997; 37: 1053. Google Scholar 32 : Dose selection for prostate cancer patients based on dose comparison and dose response studies. Int J Radiat Oncol Biol Phys2000; 46: 823. Google Scholar 33 : Preliminary results of a randomized radiotherapy dose escalation study comparing 70 Gy to 78 Gy for prostate cancer. J Clin Oncol2000; 18: 3904. Google Scholar 34 : Importance of high radiation doses (72 Gy or greater) in the treatment of stage T1–T3 adenocarcinoma of the prostate. Urology2000; 55: 85. Google Scholar 35 : Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med1997; 337: 295. Google Scholar 36 : Phase III trial of androgen suppression using goserelin in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31. J Clin Oncol1997; 15: 1013. Google Scholar 37 : Late rectal toxicity after conformal radiotherapy of prostate cancer (I): multivariate analysis and dose-response. Int J Radiat Oncol Biol Phys2000; 47: 103. Google Scholar 38 : Complications from radiotherapy dose escalation in prostate cancer: preliminary results of a randomized trial. Int J Radiat Oncol Biol Phys2000; 48: 635. Google Scholar From the Departments of Radiation Oncology, Medical Physics, Pathology and Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York© 2001 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited ByMahal B, O'Leary M and Nguyen P (2018) Hydrogel Spacing for Radiotherapy of Prostate Cancer: A Review of the LiteratureUrology Practice, VOL. 1, NO. 2, (79-85), Online publication date: 1-Jul-2014.Stone N, Stone M, Rosenstein B, Unger P and Stock R (2018) Influence of Pretreatment and Treatment Factors on Intermediate to Long-Term Outcome After Prostate BrachytherapyJournal of Urology, VOL. 185, NO. 2, (495-500), Online publication date: 1-Feb-2011.Kapoor D, Zimberg S, Ohrin L, Underwood W and Olsson C (2018) Utilization Trends in Prostate Cancer TherapyJournal of Urology, VOL. 186, NO. 3, (860-864), Online publication date: 1-Sep-2011.Stone N, Stock R, White I and Unger P (2018) Patterns of Local Failure Following Prostate BrachytherapyJournal of Urology, VOL. 177, NO. 5, (1759-1764), Online publication date: 1-May-2007.Zelefsky M, Chan H, Hunt M, Yamada Y, Shippy A and Amols H (2018) Long-Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate CancerJournal of Urology, VOL. 176, NO. 4, (1415-1419), Online publication date: 1-Oct-2006.TOUMA N, IZAWA J and CHIN J (2018) CURRENT STATUS OF LOCAL SALVAGE THERAPIES FOLLOWING RADIATION FAILURE FOR PROSTATE CANCERJournal of Urology, VOL. 173, NO. 2, (373-379), Online publication date: 1-Feb-2005.ZIETMAN A, CHUNG C, COEN J and SHIPLEY W (2018) 10-Year Outcome for Men With Localized Prostate Cancer Treated With External Radiation Therapy:: Results of a Cohort StudyJournal of Urology, VOL. 171, NO. 1, (210-214), Online publication date: 1-Jan-2004.POLLACK A, HANLON A, HORWITZ E, FEIGENBERG S, UZZO R and HANKS G (2018) Prostate Cancer Radiotherapy Dose Response: An Update of the Fox Chase ExperienceJournal of Urology, VOL. 171, NO. 3, (1132-1136), Online publication date: 1-Mar-2004.KOH H, KATTAN M, SCARDINO P, SUYAMA K, MARU N, SLAWIN K, WHEELER T and OHORI M (2018) A Nomogram to Predict Seminal Vesicle Invasion by the Extent and Location of Cancer in Systematic Biopsy ResultsJournal of Urology, VOL. 170, NO. 4 Part 1, (1203-1208), Online publication date: 1-Oct-2003.ZELEFSKY M, MARION C, FUKS Z and LEIBEL S (2018) Improved Biochemical Disease-Free Survival of Men Younger Than 60 Years With Prostate Cancer Treated With High Dose Conformal External Beam RadiotherapyJournal of Urology, VOL. 170, NO. 5, (1828-1832), Online publication date: 1-Nov-2003.Related articlesJournal of UrologyNov 9, 2018, 11:31:10 AMOUTCOME OF LOCALIZED PROSTATE CANCER Volume 166Issue 3September 2001Page: 876-881 Advertisement Copyright & Permissions© 2001 by American Urological Association, Inc.Keywordsradiation dosageprostatic neoplasmsradiotherapy, conformalriskprostateMetricsAuthor Information MICHAEL J. ZELEFSKY More articles by this author ZVI FUKS More articles by this author MARGIE HUNT More articles by this author HENRY J. LEE More articles by this author DANNA LOMBARDI More articles by this author CLIFTON C. LING More articles by this author VICTOR E. REUTER More articles by this author E.S. VENKATRAMAN More articles by this author STEVEN A. LEIBEL More articles by this author Expand All Advertisement PDF DownloadLoading ...