Dose-response for biochemical control among high-risk prostate cancer patients after external beam radiotherapy.

INTRODUCTION The literature on dose-response characteristics of high-risk prostate cancer has been scarce in this era, when these patients are treated with hormone therapy along with radiotherapy. In this study, we estimated the dose-response of prostate-specific antigen (PSA) control probability in high-risk prostate cancer patients treated with radiotherapy alone. METHODS AND MATERIALS The data set contains information on 363 high-risk prostate cancer patients who were treated with external beam radiotherapy without hormonal treatment between February 1987 and September 1998. These patients have one or more of the following adverse prognostic features: digital rectal examination stage > or =cT3, PSA >20 ng/mL, and biopsy Gleason score > or =8. These patients had biopsy-proven adenocarcinoma of prostate and were staged according to the 1992 AJCC staging system that was based on digital rectal examination. The logistic model was fitted to the data at various time points after treatment, and the dose-response parameters were estimated. RESULTS The dose required to have 50% tumor control, TCD50 (95% confidence interval), for high-risk patients is 75.5 (range: 70.7-80.2) Gy. The gamma 50 (95% confidence interval) is 1.7 (range: 0.7-2.7) around 75.5 Gy. Recursive partitioning analysis based on the null Martingale residuals identifies two subgroups within the high-risk group. The TCD50 estimates of the two subgroups (PSA < or = vs. >20 ng/mL) differ by 15 Gy at 5 years. There is a dose response in both subgroups. CONCLUSION We recognize that this study has the usual limitations of a retrospective study that includes treatment policy change that spanned a long time frame. However, our data strongly suggest a benefit of dose escalation for all the patients in the entire high-risk group. There is a steep dose response in PSA control probability around a modern dose of 78 Gy. A 5-Gy dose increase beyond 78 Gy may improve PSA control by about 10%.

[1]  S Sutlief,et al.  Brachytherapy radiation doses to the neurovascular bundles. , 2000, International journal of radiation oncology, biology, physics.

[2]  A. Pollack,et al.  External beam radiotherapy dose response of prostate cancer. , 1997, International journal of radiation oncology, biology, physics.

[3]  Michael J. Zelefsky,et al.  Comparison of the 5-Year Outcome and Morbidity of Three-Dimensional Conformal Radiotherapy Versus Transperineal Permanent Iodine-125 Implantation for Early-Stage Prostatic Cancer , 1999 .

[4]  James D. Cox,et al.  Consensus statement: Guidelines for PSA following radiation therapy , 1997 .

[5]  T. DeWeese,et al.  Long‐term effects of androgen deprivation therapy in prostate cancer patients , 2002, Clinical endocrinology.

[6]  J Halpern,et al.  27-year mortality in the Western Collaborative Group Study: construction of risk groups by recursive partitioning. , 1991, Journal of clinical epidemiology.

[7]  C C Ling,et al.  High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. , 2001, The Journal of urology.

[8]  A. V. von Eschenbach,et al.  External beam radiotherapy dose response characteristics of 1127 men with prostate cancer treated in the PSA era. , 2000, International journal of radiation oncology, biology, physics.

[9]  V. Devita,et al.  Cancer : Principles and Practice of Oncology , 1982 .

[10]  D. Grignon,et al.  Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. , 2001, International journal of radiation oncology, biology, physics.

[11]  E. Venkatraman,et al.  Normalization of serum testosterone levels in patients treated with neoadjuvant hormonal therapy and three-dimensional conformal radiotherapy for prostate cancer. , 2002, International journal of radiation oncology, biology, physics.

[12]  V. Weinberg,et al.  Dose of radiation received by the bulb of the penis correlates with risk of impotence after three-dimensional conformal radiotherapy for prostate cancer. , 2001, Urology.

[13]  George Starkschall,et al.  Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. , 2002, International journal of radiation oncology, biology, physics.

[14]  Michael J. Zelefsky,et al.  High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. , 2002, International journal of radiation oncology, biology, physics.

[15]  A. Pollack,et al.  Conventional external-beam radiation therapy alone or with androgen ablation for clinical stage III (T3, NX/N0, M0) adenocarcinoma of the prostate. , 1999, International journal of radiation oncology, biology, physics.

[16]  D. Kuban,et al.  Prostate-specific antigen for pretreatment prediction and posttreatment evaluation of outcome after definitive irradiation for prostate cancer. , 1995, International journal of radiation oncology, biology, physics.

[17]  D. Kuban,et al.  Radiation therapy for clinically localized prostate cancer: a multi-institutional pooled analysis. , 1999, JAMA.

[18]  A. Hanlon,et al.  Dose selection for prostate cancer patients based on dose comparison and dose response studies. , 2000, International journal of radiation oncology, biology, physics.

[19]  A. Hanlon,et al.  Posttreatment prostate-specific antigen nadir highly predictive of distant failure and death from prostate cancer. , 2002, International journal of radiation oncology, biology, physics.

[20]  D. Kuban,et al.  High-dose intensity modulated radiation therapy for prostate cancer , 2004, Current urology reports.

[21]  C. Ling,et al.  Risk group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer. , 2002, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[22]  C B Begg,et al.  The effect of local control on metastatic dissemination in carcinoma of the prostate: long-term results in patients treated with 125I implantation. , 1991, International journal of radiation oncology, biology, physics.

[23]  Jacques Bernier,et al.  Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial , 2002, The Lancet.

[24]  A W Partin,et al.  Serum PSA after anatomic radical prostatectomy. The Johns Hopkins experience after 10 years. , 1993, The Urologic clinics of North America.

[25]  A. Renshaw,et al.  Biochemical Outcome after radical prostatectomy, external beam Radiation Therapy, or interstitial Radiation therapy for clinically localized prostate cancer , 1998 .

[26]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[27]  A. deMoura,et al.  [Cancer of the prostate]. , 1962, Jornal do medico.

[28]  C. Reddy,et al.  Higher than standard radiation doses (> or =72 Gy) with or without androgen deprivation in the treatment of localized prostate cancer. , 2000, International journal of radiation oncology, biology, physics.

[29]  S M Bentzen,et al.  Quantifying the position and steepness of radiation dose-response curves. , 1997, International journal of radiation biology.