Important Studies Flashcards
RT vs. surgery vs. observation
ProtecT: “Hamdy et al, NEJM, 2016. “PSA detected prostate cancer (any Gleason score). Age 50-59 Median age 62. 77% Gleason 6, 20% Gleason 7, 2% Gleason 8-10, 76% with T1c”. “→Active surveillance vs. Radical prostatectomy vs. RT + 3-6 mos ADT. “•10-yr outcomes -With RT vs. surgery, there is no difference in PCM, DM, disease progression, ADT salvage, or all deaths. -AS had worse PCM, DM, disease progression, and ADT compared to RP and RT. However all cause mortality was similar. AS vs. RP vs. RT: 10-yr PCM 1.85% vs. 0.67% vs. 0.73% DM 5.6% vs. 2.4% vs. 2.7% Disease progression 20% vs. 5.9% vs. 6.6% ADT salvage 8.7% vs. 4.8% vs. 5.6% All deaths 11% vs. 10% vs. 10% Results similar in per protocol analysis •Gleason grade group subanalysis -Group 2 PCM less with RT, 2.0% RP vs. 0.8% RT -Group 3-5 PCM 2.3% vs. 2.0% -This subanalysis is likely underpowered •QOL 6-mo sexual dysfunction 95% RP vs. 88% RT Later sexual function with RT matches AS 6-mo RP incontinence 55%, 12-mo 20% 6-mo RT bowel dysfunction 5% -RT bowel function recovered later except for bloody stools. Urinary voiding and nocturia worse with RT at 6 mos then recovered to similar to other groups at 12 mos. No difference in 2nd malignancies.”
RP vs. watchful waiting
Scandinavian SPCG-4. “Bill-Axelson et al, NEJM, 2005/. “age <75, T1-T2, operable, life expectancy >10yrs, PSA<50, negative bone scan. “29-yr f/u -NNT to prevent one death: 8.3 -Mean OS absolute benefit of 2.9 yrs -ECE had 5x risk of death, Gleason 7 had 10x risk death 23-yr Death due to prostate cancer 31% WW vs. 20% RP 23-yr Any mortality 84% vs. 72% -In age <65, 34% vs. 18% deaths from prostate cancer, and less difference if age 65 or older. -Deaths from prostate cancer in intermediate risk group 39% vs. 15%. No difference in low or high risk group OS benefit in low risk age <65 23-yr DM 43% vs. 27%. Benefit in both age groups, low and int risk ADT used in 67% vs. 43%. Benefit in both age groups, and all risk groups”
Active Surveillance
Sunnybrook, Toronto. “Klotz et al, JCO, 2010 Klotz et al, JCO, 2015”. “Low or intermediate risk patients. The study later only enrolled low risk patients. “Phase II active surveillance. PSA q3mos for 2 years, then q6mos. Biopsy q12 months, then q3-4 yrs. Biopsies to initial site and anterior and anterolateral regions. Long term active surveillance in low risk prostate cancer seems acceptable, leading to high survival and low DM.
Active Surveillance in very low risk
Johns Hopkins. “Tosoian et al, JCO, 2011 Tosoian et al, JCO, 2015”. Very low risk and low risk: T1c, PSA density <0.15, GS 6 or less with 2 or less cores, <50% of any core. Long term active surveillance in very low and low risk prostate cancer seems acceptable, leading to high survival and low DM.
PSA and DRE
ERSPC and PLCO reanalysis. Tsodikov et al, Ann Intern Med, 2017. “Screening estimated to give 7-9% reduction in PCSM per year of mean lead time 11-year follow-up ERSPC: 25-31% relative benefit in PCSM PLCO: 27-32% relative benefit in PCSM” The ERSPC and PLCO screening studies show potential benefit screening for prostate cancer. Prostate, Lung, Colorectal, Ovarian (PLCO). “Andrioloe et al, NEJM, 2009. Age 55-74. “→PSA screening q6 yrs and DRE q4 yrs vs. usual care”. Screening reduced number of deaths, 22 vs. 38. 10-yr NNT 5 to prevent one death if no comorbidity. If at least 1 comorbidity, no benefit European randomized study of screening for prostate cancer (ERSPC). “Schröder et al, NEJM, 2009. Age 50-74, criteria different per country. “→PSA screening vs. no screening. Prostate cancer screening seems to reduce death from prostate cancer.
Selenium and Vitamin E
SELECT. “Lippman et al, JAMA, 2009. age 55 or older (if black, age ≥ 50), PSA≤4, negative DRE. “→Selenium + placebo vs. vitamin E + placebo vs. selenium + vitamin E vs. two placebos”. No difference in rate of prostate cancer. Vitamin E alone rates trend slightly higher (4.9% vs. ~4.5% other arms, p=0.06).
RP vs. Active Surveillance
PIVOT. “Wilt et al, NEJM, 2012. “T1-T2Nx, PSA<50, Age<75, negative bone scan, life expectancy >10 years. There is a trend to benefit in OS with surgery over observation, especially in those with intermediate risk disease. Surgery leads to notable adverse effects.
Dose Escalation
MDACC: Pollack et al, IJROBP, 2002; 70 vs. 78 GY
RTOG 0126: Michalski et al, IJROBP, 2013. 70.2 vs 79.2
MGH PROG: Zietman et al, JAMA, 2005. 70.2 vs. 79.2
MRC RT01: Dearnaley et al, Lancet Oncol, 2007. 64 vs 74
Dutch CKVO 96-10: Peeters et al, JCO, 2006. 68 vs. 78
Moderate Hypofractionation
MDACC: Hoffman et al, JCO 2018. →75.6 Gy/42 fx in 1.8 Gy vs. 72 Gy/30 fx in 2.4 Gy. Superiority
Fox Chase: Pollack et al, JCO, 2013. →76 Gy/38 fx in 2.0 Gy vs.70.2 Gy/26 fx in 2.7 Gy. Superiority
RTOG 0415: Lee et al, JCO, 2016. →73.8 Gy/41 fx in 1.8 Gy vs. 70 Gy/28 fx in 2.5 Gy. Noninferiority
CHHiP: Dearnaley et al, Lancet Oncol, 2016. →74 Gy/37 fx in 2.0 Gy vs. 60 Gy/20 fx in 3.0 Gy vs.
57 Gy/19 fx in 3.0 Gy. Noninferiority. Cannot say 57 Gy is noninferior
HYPRO - Erasmus, Netherlands. Incrocci et al, Lancet Oncol, 2016. →78 Gy/39 fx in 2.0 Gy vs.
64.6 Gy/19 fx in 3.4 Gy, 3 fx per week. Superiority.
Regina Elena NCI Rome. Arcanjeli et al, IJROBP, 2012. →80 Gy/40 fx in 2.0 Gy vs. 62 Gy/20 fx in 3.1 Gy. Superiority
PROFIT: Catton et al, JCO, 2017. →78 Gy/39 fx in 2 Gy vs. 60 Gy/20 fx in 3 Gy. Noninferiority
ultrahypofx vs. conventional
HYPO-RT-PC: Widmark et al, Lancet, 2019. intermediate (89%) and high risk (11%)
PSA < 20→42.7 Gy/ 7 fx3DCRT, IMRT, or VMAT (not SBRT) vs. 78 Gy/ 39 fx. Noninferiority. No ADT. RT in 7 fractions (3D or IMRT, not SBRT) is noninferior to conventional RT in intermediate and high risk prostate cancer. Acute toxicity was worse with SBRT but late toxicity was similar.
SBRT vs. hypofx
PACE-B: Brand et al, Lancet Oncol, 2019. Low and intermediate risk. →78 Gy/39 fx or 62 Gy/20 fx
vs. SBRT 36.25 Gy. Acute toxicity is not different between arms. Follow-up is ongoing to assess late toxicity.
NRG RTOG 0938. Lukka et al, IJROBP, 2018. low risk prostate. Phase II: 36.25 Gy/5 fx in 2.5 weeks
vs. 51.6 Gy/12 fx, 4.3 Gy per fx. Both regimens are well tolerated. A randomized trial to evaluate SBRT vs. convenational RT is warranted.
SBRT
UCLA. Kishan et al, JAMA Oncol, 2019. low risk (55%), favorable intermediate (32%) and unfavorable intermediate (12%). Analysis of pooled data from prospective Phase II trials. 33.5-40 Gy in 4-5 fractions. Long terms outcomes for SBRT for prostate cancer show high BC and low toxicity. SBRT is an appropriate option in low and intermediate risk.
UCLA. Jackson et al, IJROBP, 2019. Low, int, and high risk prostate cancer. Analysis of pooled data from prospective trials. 38 trials found. This large pooled analysis of SBRT prospective trials shows favorable bPFS and toxicity. SBRT is an appropriate treatment option.
