Recently published studiesprovide additional evidence supportingthe use of combination treatmentwith androgen deprivation and radiationin patients with locally advancedprostate cancer (PCa).
The studies demonstrate that androgendeprivation therapy (ADT) plusradiation therapy (RT) is associatedwith superior cancer-specific and overallsurvival compared with ADT alone,prompting researchers to conclude thatADT plus RT is a reasonable option fortreating locally advanced PCa.
“For patients [with locally advancedPCa] who are treated by radiation,the standard of care should beADT plus RT. Period,” said Justin E.Bekelman, MD, Associate Professor ofRadiation Oncology at the Universityof Pennsylvania in Philadelphia. “Thechallenge is, there’s never been a trialthat has compared surgery to ADTplus RT for locally advanced prostatecancer. That trial is crucial. That wouldfill the evidence gap.”
At his institution, RT plus long-termADT is the standard recommendationfor patients with locally advanced PCawho opt for RT, he said.
Manageable side effects
“I think that the important thingto note is that the combination ofradiation with hormone therapy notonly improves lives, but is tolerable,Dr. Bekelman said. “With modernradiotherapy techniques, studieshave shown that the side effects ofradiation with hormone therapy aremanageable.”
Dr. Bekelman led a study comparingADT alone and ADT plus RT in 3groups of men with locally advanced orhigh-risk PCa. These groups included acohort of 4,642 men aged 65–75 yearsin a randomized controlled trial (RCT);an elderly cohort of 8,694 men olderthan 75 years with locally advancedPCa; and a cohort of 2,017 men aged 65years and older with screen-detectedhigh-risk PCa.
In the RCT cohort, ADT plus RTwas associated with a significant 57%decreased risk of cancer-specific mortalityand 37% decreased risk of all-causemortality compared with ADTalone in propensity score-adjustedanalyses, Dr. Bekelman’s groupreported in the Journal of ClinicalOncology (2015;33:716-722). In theelderly cohort, ADT plus RT wasassociated with a significant 49% and37% decreased risk of cancer-specificand all-cause mortality, respectively.In the screen-detected cohort, ADTplus RT was associated with a significant75% and 50% decreased risk ofcancer-specific and all-cause mortality,respectively.
In a separate study, which waspublished in the Journal of ClinicalOncology (2015;33:2143-2150),Malcolm D. Mason, MD, of CardiffUniversity School of Medicine inCardiff, UK, and colleagues reportedon a study showing that men withlocally advanced PCa treated withADT plus RT had a significant 30%decreased risk of all-cause mortalityand 54% decreased risk of PCa mortalitycompared with those who receivedADT alone. The study included 1,205men with locally advanced PCa who,from 1995 to 2005, were randomlyassigned to receive ADT alone (602men) or ADT plus RT (603 men). Aftera median follow-up time of 8 years, 465patients had died, 199 from PCa.
The researchers noted that patientsin the combination arm experienceda higher frequency of adverse eventsrelated to bowel toxicity, but only 2 of589 patients had grade 3 or higher diarrheaat 24 months after RT.
Additionally, based on a recent systematicreview and meta-analysis,researchers concluded that longerduration of ADT combined withradiotherapy is associated with betteroverall, disease-free, and disease-specific survival in patientswith intermediate- and high-risknon-metastatic PCa. The researchers,who published their findings inthe International Brazilian Journal ofUrology (2015;41:425-434), analyzedpooled data from 6 randomized trialscomparing different durations of hormoneblockade.
‘Sometimes a contentious area’
In an interview, Dr. Mason said hebelieves ADT plus RT is the standardof care for locally advanced PCa. “Thisis sometimes a contentious area inthat the results of surgery in properlyselected men treated in expert centersare undoubtedly excellent, too, thoughthere is no level 1 evidence to supportthis,” he said.
Dr. Mason added, “We badly need atrial of radiotherapy plus hormones versussurgery in locally advanced disease,but the challenges in doing such a trialare formidable. Our trial and othersare sometimes interpreted as indicatingthat curative local therapy iseffective in men with locally advanceddisease, whatever form of curativetherapy is employed. Now, this may betrue, but it is an assumption, and it isnot the only possible explanation forour study results.”
In a study of men with clinicallynode-positive (cN+) prostate cancer(PCa), researchers led by JasonA. Efstathiou, MD, DPhil, of theDepartment of Radiation Oncologyat Massachusetts General Hospitalin Boston, found that ADT plus RTwas associated with a significant 50%decreased risk of 5-year all-cause mortalitycompared with ADT alone inpropensity score-adjusted analyses.
This study, which was publishedin the Journal of the National CancerInstitute (2015;107:djv119), included3,540 men with cN+ PCa identifiedusing the National Cancer Data Base.Of these, 1,818 (51.4%) received ADTplus RT, 1,141 (32.2%) received ADTalone, 220 (6.2%) received RT alone,and 361 (10.2%) received neither ADTnor RT. The propensity score-adjustedanalysis, which was performed to balancebaseline characteristics, included318 ADT-only recipients matched to318 ADT plus RT recipients.
Important clinical implications
“As aggressive local management ofcN+ prostate cancer may lead to durabledisease control and even cure,” theauthors concluded, “these data haveimportant implications for clinical practiceguidelines and staging systems.”
Prior to propensity score matching,47.1% of patients who received ADTalone and 25% of those treated withADT plus RT died within the 5-year follow-up period. The crude 5-year overallsurvival rate was significantly lower inthe ADT-only group compared with theADT plus RT group (49.4% vs. 72.4%).
The men had a median age of 66years. The median follow-up time was5.2 years for patients diagnosed from2004 to 2006 and 2.7 years for thosediagnosed from 2004 to 2011, theresearchers reported.
Data showed that the use of ADT alonedecreased from 36.6% in 2004 to 32.2%in 2011, whereas use of ADT plus RTincreased from 45.2% to 54.1%.