Radiation Oncology/RTOG Trials/8610

RTOG 86-10 (PROSTATE)
 * Title: Androgen Deprivation Adjuvant to Definitive Radiotherapy in Locally Advanced Carcinoma of the Prostate
 * Objectives:
 * (1) Compare locoregional tumor control in patients with clinical Stages B2 and C carcinoma of the prostate treated with radiotherapy alone vs. zoladex/flutamide prior to and during radiotherapy.
 * (2) Compare tumor clearance rates, disease-free survival, survival, time to appearance of metastasis, serum testosterone levels, sexual function, and toxicity/morbidity of treatment in these two treatment groups.
 * Protocol_NCI:
 * Arm 1: 70 Gy EBRT only
 * Arm 2: AST x2 months followed by 70 Gy EBRT + concurrent AST
 * Eligibility: Bulky (clinically palpable > 25 cc) T2-T4, N+ allowed
 * Enrolled: 471 patients, 456 analyzable
 * Activated: April 15, 1987
 * Closed: June 1, 1991
 * Conclusion:
 * PMID 18172188 -- Short-Term Neoadjuvant Androgen Deprivation Therapy and External-Beam Radiotherapy for Locally Advanced Prostate Cancer: Long-Term Results of RTOG 8610. (Roach M, JCO 2008). Conclusion: The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events.
 * PMID 11483335 -- Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. (Pilepich MV, IJROBP 2001). 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.
 * Publications:
 * ASCO Abstract -- Stat3 as a correlate of distant metastasis in RTOG 86-10 (Torres-Roca JF, ASCO 2005). Conclusion: Stat3 activity is correlated with the development of distant metastasis in prostate cancer. This marker should be further evaluated in a larger cohort of patients.
 * PMID 15217948 -- Ki-67 staining index predicts distant metastasis and survival in locally advanced prostate cancer treated with radiotherapy: an analysis of patients in radiation therapy oncology group protocol 86-10. (Li R, Clin Cancer Res 2004). Conclusion: Higher Ki-67 SI was significantly associated with a greater risk of DM and DSS in locally advanced prostate cancer after definitive EBRT or AD + EBRT.
 * ASCO Abstract -- Influence of Number of CAG Repeats on Local Control in the RTOG 86-10 Protocol (Abdel-Wahab M, ASCO 2004). Conclusion: Measurement of CAG repeats may aid in selection of patients who achieve local control benefit from androgen deprivation.
 * ASTRO Abstract -- MDM2 as a Predictor of Prostate Cancer Outcome: An Analysis of RTOG 8610 (Khor, ASTRO 2004). Conclusion: Positive MDM2 expression was associated significantly with Gleason score and, although not significant, an increased risk of distant metastasis. While the relationship of MDM2 overexpression to DM was not statistically significant, this observation may be clinically meaningful. The cohort examined was small and with larger patient numbers, MDM2 overexpression may emerge as a significant covariate. In addition, MDM2 overexpression, like p53, may potentially be more discriminating in men with more favoravle risk prostate cancer.
 * PMID 12947069 -- Loss of p16 expression is of prognostic significance in locally advanced prostate cancer: an analysis from the Radiation Therapy Oncology Group protocol 86-10. (Chakravarti A, JCO 2003). Conclusion: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.
 * PMID 12663710 -- Prostate cancer DNA ploidy and response to salvage hormone therapy after radiotherapy with or without short-term total androgen blockade: an analysis of RTOG 8610. (Pollack A, JCO 2003). Conclusion: Nondiploidy was associated with shorter survival, which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB.
 * PMID 12478146 -- Race and survival of men treated for prostate cancer on radiation therapy oncology group phase III randomized trials. (Roach, J Urol 2003). Conclusion: As previously reported, tumor grade (Gleason score), palpation T stage, lymph node status, pretreatment PSA and treatment type are major predictors of overall and disease specific survival. We noted no evidence that race has independent prognostic significance in patients treated for prostate cancer in Radiation Therapy Oncology Group prospective randomized trials.
 * ASTRO Abstract -- Vascular endothelial growth factor (VEGF) expression in locally advanced prostate cancer (LAPC): secondary analysis of radiation therapy oncology group (RTOG) 8610. (Hughes, ASTRO Abstract 128, 2003; Int J Radiat Oncol Biol Phys 57 (2 Suppl): S201-2, 2003). Conclusion: This analysis represents one of the largest sample bases reviewed for VEGF expression in human prostate carcinoma patients. VEGF is highly expressed in this study population. Although no statistically significant correlation was seen between extent of VEGF expression and outcomes for patients randomized in RTOG 8610, VEGF will be further investigated as a high priority biomarker for patients from RTOG 9202 to add a broader distribution of prostate cancer patients with regard to GS for analysis. Further study will include biological correlation of VEGF IS with microvessel density in the RTOG 8610 patients.
 * ASTRO Abstract -- Monte Carlo Simulation of a Markov Model for a Phase III Clinical Trial Evaluating the Addition of Total Androgen Suppression (TAS) To Radiation Versus Radiation Alone for Locally Advanced Prostate Cancer (RTOG 86−10) (Konski, ASTRO Abstract 151, 2003; Int J Radiat Oncol Biol Phys 57 (2 Suppl): S215-6, 2003). Conclusion: Our analysis shows that adding hormonal treatment to RT improves both health outcomes and lowers costs. The expected cost is lowered by preventing failures in the future and obviating the need for additional therapies, such as hormones and chemotherapy. Despite producing lower quality of life in the short term, hormonal therapy reduces the cost and morbidity associated with future treatment failures.
 * PMID 12459350 -- Effect of a short course of neoadjuvant hormonal therapy on the response to subsequent androgen suppression in prostate cancer patients with relapse after radiotherapy: a secondary analysis of the randomized protocol RTOG 86-10. (Shipley WU, IJRBOP 2002) Conclusion: Although a 4-month course of neoadjuvant and concurrent maximum androgen suppression and RT (compared with RT alone) significantly increases the freedom from relapse rate and freedom from receiving salvage HT, it does not compromise the long-term beneficial effect of subsequent salvage HT, if needed for relapse. These findings with long follow-up in patients treated for locally advanced disease diagnosed 9-14 years previously should help allay concerns of the possible development of "resistance" to androgen suppression when 4-month courses of neoadjuvant HT are used before primary treatment.
 * ASTRO Abstract -- Cyclooxygenase 2 (COX-2) Expression in Locally Advanced Prostate Cancer: Secondary Analysis of Radiation Therapy Oncology Group (RTOG) 86-10. (Hughes L, ASTRO 2002, Int J Radiat Oncol Biol Phys [54] (2):271-272, 2002.). Conclusion: This analysis represents the largest sample base reviewed for COX-2 expression in prostate carcinoma patients. COX-2 is highly expressed in this study population. Patients with GS 7–10 locally advanced prostate cancer had greater intensity of COX-2 expression when compared with their lower GS counterparts. Due to the large degree of COX-2 expression seen in prostate carcinoma, COX-2 will be a high priority biomarker when evaluating samples from RTOG 92-02.
 * PMID 11240235 -- Subset analysis of RTOG 85-31 and 86-10 indicates an advantage for long-term vs. short-term adjuvant hormones for patients with locally advanced nonmetastatic prostate cancer treated with radiation therapy. (Horwitz EM, IJRBOP 2001). Conclusion: Adjuvant long-term hormones compared to short-term hormones resulted in statistically significant improvements in bNED control, DMF, and CSF rates for patients with locally advanced nonmetastatic prostate cancer.
 * ASCO Abstract -- A Secondary Analysis of RTOG 86-10: Does the Extent of Progression at the Time of Initiating Salvage Hormone Therapy Influence Survival in Patients with Prostate Cancer Who Failed Initial Treatment with Irradiation? (Shipley WU, ASCO 2001). Conclusion: For those patients that relapsed following irradiation and were treated with salvage HT, a more advanced extent of progression at the time of initiating salvage HT, decreased significantly disease specific survival and overall survival in this retrospective analysis. These findings warrant confirmation by a second independent study.
 * PMID 10837944 -- Predicting long-term survival, and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials. (Roach M, IJRBOP 2000). Conclusion: Based on this meta-analysis of RTOG trials, subsets of patients can be identified who either do not appear to benefit from the use of hormonal therapy, benefit from short-term hormonal therapy, or who benefit only from long-term hormonal therapy. These observations should be confirmed by prospective randomized trials before they can be considered conclusive. In the meantime, however, these observations provide rational guidelines for deciding who should receive hormonal therapy and for how long.
 * PMID 10837943 -- Four prognostic groups predict long-term survival from prostate cancer following radiotherapy alone on Radiation Therapy Oncology Group clinical trials. (Roach, IJRBOP 2000). Conclusion: Recognition of these four risk groups provides a basis for estimating the long-term DSS for men treated with XRT alone and should facilitate the design of future prospective randomized trials.
 * Anderson PR, Winter KA, Hanks GE, et al.: Gleason score 4+3 prostate cancer patients have worse bNED outcome compared to Gleason score 3+4 treated with radiation therapy alone: subset analysis of RTOG 85-31 and 86-10. Int J Radiat Oncol Biol Phys 48(3 suppl): A-187, 205-206, 2000.
 * Shipley W, Lu JD, Pilepich MV, et al.: Does neoadjuvant hormone treatment compromise subsequent androgen suppression in prostate cancer patients who fail initial radiation therapy: a secondary analysis of RTOG-8610. Int J Radiat Oncol Biol Phys 48(3 suppl): A-115, 169-170, 2000.
 * PMID 10894874 -- Survival advantage from higher-dose radiation therapy for clinically localized prostate cancer treated on the Radiation Therapy Oncology Group trials. (Valicenti, JCO 2000). Conclusion: These data demonstrate that higher-dose radiation therapy can significantly reduce the risk of dying from prostate cancer in men with clinically localized disease. This survival benefit is restricted to men with poorly differentiated cancers.
 * Horwitz EM, Winter K, Hanks GE, et al.: Long-term outcome for patients with locally advanced non-metastatic prostate cancer treated with adjuvant hormones and radiation therapy versus radiation therapy alone: subset analysis of RTOG 85-31 and 86-10. Int J Radiat Oncol Biol Phys 45(3 suppl): A142, 220-221, 1999.
 * PMID 10022702 -- Long-term survival after radiotherapy alone: radiation therapy oncology group prostate cancer trials. (Roach M, J Urol 1999). Conclusion: In the first 10 years Gleason score was the single most important predictor of death. Gleason score should be incorporated into the current clinical staging system.
 * Scott C, Roach M, Lawton C, et al.: Q-twist analysis for prostate cancer treated with radiation therapy with or without hormonal therapy: RTOG 86-10. Qual Life Res 8(7): A48, 568, 1999.
 * ASCO Abstract -- Radiation Dose-Response Is Gleason Score Dependent on the Radiation Therapy Oncology Group Prostate Cancer Trials (Meeting abstract). (Valicenti R, ASCO 1999). Conclusion: These data suggest a significant effect for higher radiation dose to reduce the probability of dying from prostate cancer in men with poorly differentiated disease.
 * Hammond EH, Lu JD, Doggett RL, et al.: Microvessel density in prostatic biopsies in a phase III trial (RTOG 86-10). Lab Invest 78: A-481, 84a, 1998.
 * Pilepich ML, Winter K, Roach M, et al.: Phase III Radiation Therapy Oncology Group (RTOG) trial 86-10 of androgen deprivation before and during radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys 42(suppl 1): A105, 177, 1998.
 * Roach M, Lu J, Pilepich M, et al.: Long term survival in 1500 men treated for prostate cancer with radiotherapy alone (XRT): based on radiation therapy oncology group protocols 7706, 7506, 8531, and 8610. [Abstract] Proceedings of the American Urological Association 1998.
 * ASCO Abstract -- Prognostic Subgroups Predict Disease Specific Survival for Men Treated With Radiotherapy Alone On Radiation Therapy Oncology Group (RTOG) Prostate Cancer Trial. (Roach M, ASCO 1998). Conclusion: Recognition of these four prognostic subgroups should allow estimates to be made of the long term DSS of men treated with radiotherapy alone for CAP.
 * PMID 8998185 -- p53 status and prognosis of locally advanced prostatic adenocarcinoma: a study based on RTOG 8610. (Grignon DJ, J Natl Cancer Inst. 1997). Conclusion: Determination of p53 protein expression status yield significant, independent prognostic information concerning the development of distant metastases, progression-free survival, and overall survival for patients with locally advanced prostate cancer who are treated primarily with radiation therapy. The interaction of radiation therapy plus hormone therapy and abnormal p53 protein expression may provide a clinical link to experimental evidence that radiation therapy and/or hormone therapy act, at least in part, by the induction of apoptosis (a cell death program) and suggests that this mechanism may be blocked in patients whose tumors have p53 mutations.
 * Grignon D, Pajak T, Hammond E, et al.: Application of the gleason grading system: a comparison of institutional and central review grading using RTOG protocols 85-31 and 86-10. [Abstract] Proceedings of the United States and Canadian Academy of Pathology Meeting 9(1): A418, 73a, 1996.
 * Grignon D, Won M, Hammond E, et al.: DNA content as a prognostic indicator in prostate cancer (PCA): a study based on RTOG protocol 86-10. [Abstract] Proceedings of the United States and Canadian Academy of Pathology Meeting 9(1): A419, 75a, 1996.
 * Grignon D, Caplan R, Sarkar F, et al.: p53 suppressor gene mutations predict for failure following combined neoadjuvant total androgen ablation and external beam radiation therapy for locally advanced prostate cancer: a study based on RTOG protocol 86-10. [Abstract] Proceedings of the American Urological Association 153(suppl 1): A293, 1995.
 * PMID 7716842 -- Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma: a randomized comparative trial of the Radiation Therapy Oncology Group. (Pilepich MV, Urology 1995). Conclusion: Short-term androgen deprivation with radiation therapy results in a marked increase in local control and disease-free survival compared with pelvic irradiation alone in patients with locally advanced carcinoma of the prostate. Long-term surveillance is required to assess effects on overall survival.
 * Pilepich MV, Krall J, Al-Sarraf M, et al.: A phase III trial of androgen suppression before and during radiation therapy (RT) for locally advanced prostatic carcinoma: preliminary report of RTOG protocol 8610. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-703, 229, 1993.
 * Pilepich MV, Winter K, Byhardt R, et al.: Androgen ablation adjuvant to definitive radiotherapy in carcinoma of the prostate: year 2000 update of RTOG phase III studies 86-10 and 85-31. Int J Radiat Oncol Biol Phys 48(3 suppl): A-114, 169.