Androgen Ablation Therapy Does not Increase the Risk of Late Morbidity following 3D-conformal Radiotherapy of Organ-confined Prostate Cancer: The Experience of the European Institute of Oncology

Aims and Background Androgen ablation therapy in conjunction with radiotherapy-neoadjuvant and adjuvant – has consistently been shown to be associated with improved biochemical and local control, whereas controversy still remains as regards its benefit in terms of overall survival. The objective of this study is to determine the impact of androgen ablation in combination to 3D-conformal radiotherapy on late treatment-related toxicity. Methods 236 patients were treated with 3D-conformal radiotherapy to a total dose ranging from 70 and 78.6 Gy. Fifty-six patients did not receive any form of androgen ablation whereas 176 were given at least 3 months of neoadjuvant androgen ablation. Of these, 64 stayed on androgen ablation for a median time of 6 months post-radiotherapy. Acute toxicity was evaluated weekly during the course of treatment. Late toxicity was assessed at 3-months intervals during the follow-up. Toxicity was scored according to the RTOG criteria. Results The median follow-up was 24.6 months (range, 12-62). The incidence of late genitourinary toxicity was: 3% G2, 3.5% G3, 0.5% G4. The incidence of late gastrointestinal toxicity was: 12% G2, 2% G3, 1% G4. No association was observed between the use of androgen ablation and late treatment-related toxicity. High-risk patients who continued on androgen ablation long-term were not found to have an increased risk of developing late toxicity with respect to those who never had any form of androgen ablation or those only treated neoadjuvantly. Conclusions In our experience, the use of androgen ablation does not impact on late toxicity following high dose 3D-conformal radiotherapy for prostate cancer.

[1]  M. Keyes,et al.  Impact of neoadjuvant androgen ablation and other factors on late toxicity after external beam prostate radiotherapy. , 2004, International journal of radiation oncology, biology, physics.

[2]  Roberto Orecchia,et al.  Finding dose-volume constraints to reduce late rectal toxicity following 3D-conformal radiotherapy (3D-CRT) of prostate cancer. , 2003, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[3]  C. Reddy,et al.  Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: a large single-institution experience with radical prostatectomy and external-beam radiotherapy , 2003 .

[4]  A. Hanlon,et al.  Late morbidity profiles in prostate cancer patients treated to 79-84 Gy by a simple four-field coplanar beam arrangement. , 2003, International journal of radiation oncology, biology, physics.

[5]  George Starkschall,et al.  Late rectal toxicity: dose-volume effects of conformal radiotherapy for prostate cancer. , 2002, International journal of radiation oncology, biology, physics.

[6]  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.

[7]  Franca Foppiano,et al.  Relationships between DVHs and late rectal bleeding after radiotherapy for prostate cancer: analysis of a large group of patients pooled from three institutions. , 2002, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[8]  M. Zelefsky,et al.  Intensity-modulated radiation therapy for prostate cancer. , 2002, Seminars in radiation oncology.

[9]  G. Sanguineti,et al.  Adjuvant androgen deprivation impacts late rectal toxicity after conformal radiotherapy of prostate carcinoma , 2002, British Journal of Cancer.

[10]  C. Catton,et al.  Factors influencing risk of acute urinary retention after TRUS-guided permanent prostate seed implantation. , 2002, International journal of radiation oncology, biology, physics.

[11]  A. Hanlon,et al.  Defining the optimal radiation dose with three‐dimensional conformal radiation therapy for patients with nonmetastatic prostate carcinoma by using recursive partitioning techniques , 2001, Cancer.

[12]  S. Castiglioni,et al.  3D-Conformal Radiation Therapy in Prostate Cancer. Technical Considerations after 5 Years of Experience and 334 Patients Treated at the Istituto Europeo Di Oncologia of Milan, Italy , 2001, Tumori.

[13]  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.

[14]  D. Grignon,et al.  [Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials]. , 2001 .

[15]  R. Pötter,et al.  Rectal sequelae after conformal radiotherapy of prostate cancer: dose-volume histograms as predictive factors. , 2001, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[16]  G. Hanks,et al.  Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate. , 2001, International journal of radiation oncology, biology, physics.

[17]  G J Kutcher,et al.  Late rectal bleeding after conformal radiotherapy of prostate cancer. II. Volume effects and dose-volume histograms. , 2001, International journal of radiation oncology, biology, physics.

[18]  T L Phillips,et al.  Toxicity following high-dose three-dimensional conformal and intensity-modulated radiation therapy for clinically localized prostate cancer. , 2001, Urology.

[19]  C. Ling,et al.  Analysis of biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer using dose-distribution variables and tumor control probability models. , 2000, International journal of radiation oncology, biology, physics.

[20]  C. Ling,et al.  Late rectal toxicity after conformal radiotherapy of prostate cancer (I): multivariate analysis and dose-response. , 2000, International journal of radiation oncology, biology, physics.

[21]  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.

[22]  F. Vicini,et al.  A comparison of external beam radiation therapy versus radical prostatectomy for patients with low risk prostate carcinoma diagnosed, staged, and treated at a single institution , 2000, Cancer.

[23]  A. Markoe,et al.  Preliminary report of toxicity following 3D radiation therapy for prostate cancer on 3DOG/RTOG 9406. , 2000, International journal of radiation oncology, biology, physics.

[24]  M. Zelefsky,et al.  Long term tolerance of high dose three‐dimensional conformal radiotherapy in patients with localized prostate carcinoma , 1999, Cancer.

[25]  T E Schultheiss,et al.  Survival advantage for prostate cancer patients treated with high-dose three-dimensional conformal radiotherapy. , 1999, The cancer journal from Scientific American.

[26]  I J Das,et al.  Treatment plan evaluation using dose-volume histogram (DVH) and spatial dose-volume histogram (zDVH). , 1999, International journal of radiation oncology, biology, physics.

[27]  D. Grignon,et al.  Long-term survival after radiotherapy alone: radiation therapy oncology group prostate cancer trials. , 1999, The Journal of urology.

[28]  A. Hanlon,et al.  Diabetes mellitus: a predictor for late radiation morbidity. , 1999, International journal of radiation oncology, biology, physics.

[29]  C. Iselin,et al.  Radical perineal prostatectomy: oncological outcome during a 20-year period. , 1999, The Journal of urology.

[30]  C. Ling,et al.  Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. , 1999, International journal of radiation oncology, biology, physics.

[31]  J. Damber,et al.  Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study. , 1998, The Journal of urology.

[32]  T E Schultheiss,et al.  Dose escalation with 3D conformal treatment: five year outcomes, treatment optimization, and future directions. , 1998, International journal of radiation oncology, biology, physics.

[33]  B. Chauvet,et al.  [Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin]. , 1998, Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique.

[34]  A. Hanlon,et al.  Prostate cancer patient subsets showing improved bNED control with adjuvant androgen deprivation. , 1997, International journal of radiation oncology, biology, physics.

[35]  M. Piérart,et al.  Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. , 1997, The New England journal of medicine.

[36]  M. Zelefsky,et al.  Neoadjuvant androgen ablation prior to radiotherapy for prostate cancer: reducing the potential morbidity of therapy. , 1997, Urology.

[37]  A. Zietman,et al.  Neoadjuvant androgen suppression with radiation in the management of locally advanced adenocarcinoma of the prostate: experimental and clinical results. , 1997, Urology.

[38]  A. Fortin,et al.  Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer. , 1997, International journal of radiation oncology, biology, physics.

[39]  M. Roach Neoadjuvant therapy prior to radiotherapy for clinically localized prostate cancer. , 1997, European urology.

[40]  M M Urie,et al.  Conformal irradiation of the prostate: estimating long-term rectal bleeding risk using dose-volume histograms. , 1996, International journal of radiation oncology, biology, physics.

[41]  M. Zelefsky,et al.  Neoadjuvant hormonal therapy improves the therapeutic ratio in patients with bulky prostatic cancer treated with three-dimensional conformal radiation therapy. , 1994, International journal of radiation oncology, biology, physics.

[42]  P. Rubin,et al.  Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706. , 1991, International journal of radiation oncology, biology, physics.