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Howard Sandler

Combined Modality Treatment of Locally Advanced Prostate Cancer: Radiation Therapy (RT) with Concurrent Androgen Deprivation Therapy (ADT). Howard Sandler. What is the issue with RT?. Local control Can’t ask more from surgery or RT

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Howard Sandler

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  1. Combined Modality Treatment of Locally Advanced Prostate Cancer: Radiation Therapy (RT) with Concurrent Androgen Deprivation Therapy (ADT) Howard Sandler

  2. What is the issue with RT? • Local control • Can’t ask more from surgery or RT • If local failure after RT is low, then what would surgery add? • Morbidity is also an issue

  3. Multiple Clinical Trials Examining RT+ADT

  4. Chronology • RT alone • RT + short-term androgen deprivation (STAD) • RT + long-term androgen deprivation (LTAD) • RT + LTAD v. RT + STAD? • LTAD alone v. RT + LTAD? • Toxicity concerns

  5. RT Alone • Even early trials suggest lack of efficacy of low dose RT monotherapy for locally advanced prostate cancer

  6. RT + STAD vs. RT • Concerns about potential detrimental tumor-protective effects of AD during RT. • RTOG 8610 - 10 yr BF rates: 65% vs. 80% - 10 yr OS rates: 43% vs. 34% (p = .12) - 10 yr CV events: 12% vs. 9% (p = .32) BF = biochemical failure; CV = fatal cardiovascular events; OS = overall survival Roach M et al. J Clin Oncol 2008;26(4):585-91.

  7. RT + LTAD vs. RT • LTAD and micrometastases? • EORTC 22863 (PI: Bolla) - 3 yrs vs. no AD • 5 yr OS: 78% vs. 62% • 5 yr BFS: 76% vs. 45% • 82 of 109 patients had testosterone “renormalize” BFS = biochemical disease-free survival Bolla M et al. Lancet 2002;360(9327):103-6.

  8. RT + LTAD vs. RT + STAD • How much AD is needed? - Driven by toxicity issues • RTOG 92-02 - No 10 yr OS advantage with LTAD - All other endpoints positive - Subset of patients with Gleason score (Gl) of 8-10 had 10 yr OS benefit: 45% vs. 32% Horwitz EM et al. J Clin Oncol 2008;26(15):2497-504.

  9. RT + LTAD vs. RT + STAD • EORTC 22961 noninferiority design • 970 randomized between 1997-2002 (randomization after 6 mos of AD) • 77% T3-T4, 8% cN+ or pN+, median PSA 18, 18% Gl 8-10 (22% Gl 2-5) • 5 yr mortality: 15% vs. 19% (p = 0.65 for noninferiority) • 5 yr CV events: 3% v 4% Bolla M et al. N Engl J Med 2009;360(24):2516-27.

  10. LTAD vs. LTAD + RT? • Two randomized trials testing whether local treatment adds to AD(small neg trial 1980-1985 MRC PR02) • SPCG-7 (PI-Widmark) • 875 pts, 78% T3, 18% WHO III, median PSA 16, most pN0 • 10 yr PSM 24% vs. 12% • 10 yr Mortality 39% vs. 30% PSM = prostate cancer-specific mortality Widmark A et al. Lancet 2009;373(9660):301-8.

  11. LTAD + RT vs. LTAD? • Canadian Trial NCIC CTG PR.3 • 1205 randomized - 88% T3-T4, 18% Gl 8-10, 25% PSA > 50 • 7 yr OS: 74% vs. 66% • #CV events: 24 vs. 24 Warde PR et al. Proc ASCO 2010;Abstract CRA4504.

  12. Brachytherapy? • HDR may offer local intensification. Does this mitigate need for AD? • No randomized studies • Merrick, et al. looked at 204 “high risk” PCa pts treated with brachy plus EBRT. 119 had AD, either STAD or LTAD • Median PSA = 10, median Gl = 8 • Better bPFS with AD (80% without AD vs. 95% for AD ≤6 mos vs. 90% for AD >6 mos, p = 0.03) bPFS = biochemical progression-free survival Merrick GS et al. Int J Radiat Oncol Biol Phys 2007;68(1):34-40.

  13. Summary • RT and AD both important for locally advanced prostate cancer • LTAD better than STAD for locally advanced disease • Randomized trials have not identified a significant increase in CV events • Will higher RT doses mitigate a need for AD? • How will newer AD therapies be integrated?

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