Important Studies Flashcards
Adjuvant/ Salvage RT vs. obs
Loyola: Shaikh et al, Am J Clin Oncol, 2018. pT3 or positive margin →adjuvant RT [some PSAs >1] vs. wait and see. Ajuvant/salvage RT reduces DM and improves bPFS, cPFS, and ADT-FS. RT has acceptable toxicity.
SWOG/ RTOG 9019/ INT-0086. “Thompson et al, JAMA, 2006. Moinpour et al, JCO, 2008. Thompson et al, J Urology, 2009”“SVI, ECE, or positive margins, any PSA level allowed. [About 1/3 had PSA over 0.2, and 5-10% had PSA over 1]” →adjuvant 60-64 Gy RT to prostate bed [some PSAs >1] vs. wait and see [delayed salvage RT in 33%, at median PSA 1.0]. 10-yr BPFS 58% vs. 28%. OS and DMFS change seen at 15 years. 10-yr OS 66% vs. 74%. 15-yr OS 37% vs. 47%. Adjuvant RT improves OS and reduces DM.
ARO 96-02/ AUO AP 09/95. “Wiegel et al, JCO, 2009
Wiegal et al, Eur Urol, 2014”. “pT3N0. Positive or negative margins allowed undetectable PSA (<0.1). “→adjuvant 60 Gy to prostate bed [PSA <0.1 required] vs. wait and see. RT was strongly rec in obs arm at PSA rise. 5-yr BPFS 72% RT vs. 54%, 10-yr BPFS 56% vs. 35%. Adjuvant RT improves BPFS. There was no benefit in OS or DM.
EORTC 22911. “Bolla et al, Lancet, 2005. “pT2-T3N0 with either positive margin, ECE, or SVI. PSA ≤0.4. →adjuvant 50 Gy to prostate bed +10 Gy boost [some PSAs <0.4] vs.
wait and see [delayed salvage RT in 55%, at median PSA 1.7. Salvage RT 70 Gy given in obs for biochemical or clinical failure. Adjuvant RT improves BPFS. There was no benefit in OS or DM.
Salvage vs. Adjuvant
TROG RAVES. Kneebone et al, ASTRO, 2019. “positive margins or pT3. PSA ≤0.10. →early RT 64 Gy vs. salvage RT at ≥0.2 [triggered in 50%]. No ADT. WPRT not permitted. “50% in the wait and see arm had salvage RT
5-yr BPFS 86% vs. 88%. 8-yr BPFS 79% vs. 76%. grade ≥2 toxicity worse in adjuvant. “Adjuvant and early salvage RT were not found to be noninferior. Results seemed favorable in both arms. With salvage RT, 50% avoided RT and GU toxicity was decreased.
RADICALS (MRC/NCIC). Parker et al, ESMO, 2019. pT3/T4, GS 7-10, pre-op PSA ≥10, or positive margins. PSA ≤0.2 . RT: early RT vs. RT at PSA failure; ADT: none vs. 6 mos vs. 24 mos. RT 66 Gy/ 33 fx or 55.2 Gy/ 20 fx. WPRT 56 Gy optional; ADT: Can randomize between all three ADT or just two. “8-yr BPFS not different, DM outcomes pending
1/3 recieved hypofx. GU incontinence 5.3% vs. 2.7%. There is no difference in BPFS between adjuvant RT and early salvage RT.
ARTISTIC. Vale et al, ESMO, 2019. “positive margins, T2-T4. PSA >0.1. Prospectively planned meta-analysis of RADICALS, RAVES, and GETUG/AFU 17 with planned subanalyses. “There is a potential difference in 5-yr BPFS of 1% in favor of early salvage RT. Pending: OS and DM outcomes, subanalyses. There is no difference in BPFS between adjuvant RT and early salvage RT.
Salvage RT outcomes
Taussig Cancer Institute, Cleveland clinic, 10 institutions. Tendulkar et al, JCO, 2016. Node negative salvage prostate radiotherapy patients. “Nomogram to predict BF and DM after salvage or adjuvant RT was generated. Early salvage RT improves BC and DM.
Salvage RT +/- ADT
RTOG 9601. “Shipley et al, JCO, 2017. “pT3N0 or T2N0 with positive margins, with elevated PSA 0.2-4.0 after RP 33% T2 and 67% T3. 88% had PSA nadir <0.5, 85% with PSA<1.6, and 15% with PSA value 1.6-4. PSA failure defined as >0.5 if PSA was 0, or >0.3 above nadir. “→RT 64.8 Gy alone vs. RT with 24 mos bicalutamide conc and adj. BPFS improvement in GS<7, GS 7, and GS 8-10
12-yr OS improved 76% vs. 71%. No OS or DM benefit in PSA ≤0.06. “Adding bicalutamide to RT improves FFP, OS, CSS, and DM. There was no OS benefit with bicalutamide in PSA ≤0.6.”
GETUG-AFU 16. “Carrie et al, Lancet, 2016. pT2-T4a (bladder neck only) with rising PSA of 0.2-2.0. “→66 Gy RT alone vs. RT with 6 mos ADT. Endpoints: PFS, OS. 5, 10-yr PFS 62%/49% vs. 80%/64% ADT. 10-yr DM 31% vs. 25% ADT. No change in OS. Adding ADT to salvage radiation improves DM and PFS.
Salvage ADT and WPRT
SPPORT RTOG 0534: Pollack et al, ASTRO, 2018. PSA ≥0.1 and <2.0, and T3N0/Nx, T2N0/Nx, with or without positive margin, Gleason ≤9. “→prostate bed RT 64.8-70.2 Gy
vs. PB RT 64.8-70.2 Gy + 4-6 mos ADT vs. WPRT 45 Gy + PB RT to 64.8-70.2 Gy + 4-6 mos ADT. PO RT, and addition of ADT and WPRT lead to incremental improvements in FFP in salvage RT.
