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Long-Term ADT With Radiation Helps Prevent Post-Prostatectomy Metastases

<ѻý class="mpt-content-deck">— However, no benefit seen with short-term hormone therapy versus radiotherapy alone
MedpageToday

PARIS -- In men undergoing radiotherapy after radical prostatectomy, 2 years of androgen deprivation therapy (ADT) improved outcomes when compared with a shorter course of ADT, according to results from the trial.

At a median follow-up of more than 9 years, investigators found that the longer ADT duration improved metastasis-free survival (MFS) compared with a 6-month course (HR 0.77, 95% CI 0.61-0.97, P=0.03), with a 10-year MFS rate of 78% versus 72%, respectively.

"However, short-course hormone therapy compared with no hormone therapy did not meaningfully improve metastasis-free survival," reported Chris Parker, MD, of the Institute of Cancer Research in London, during a session at the annual congress of the European Society for Medical Oncology (ESMO).

The 6-month course of ADT with postoperative radiotherapy resulted in comparable 10-year MFS rates versus radiotherapy alone (80% vs 79%; HR 0.89, 95% CI 0.69-1.14).

ESMO discussant Silke Gillessen, MD, of the Oncology Institute of Southern Switzerland in Bellinzona, pointed out that while the trial showed that adding long-term ADT resulted in an improvement in MFS compared to a short-term course, "a majority of patients in RADICALS-HD did well with short-term ADT."

"It seems clear that some patients will benefit from short ADT versus no ADT, and some from long ADT versus short ADT," said Gillessen. "So the real question is, how do we better personalize therapy?"

Two potential approaches for determining benefit are the use of genomics and artificial intelligence based on pathology slides, she said. "Until these predictive tests are further validated, and widely available, we'll have to consider a combination of clinical factors, including age, comorbidities, patient preference, Gleason score, PSA doubling time, pre-salvage radiotherapy PSA, positive margins, and T stage, to decide on the addition of ADT."

ADT is not without toxicity, Gillessen noted, "so quality-of-life data will be interesting. Important is patient preference. One must balance between side effects of long-term ADT and the reduction of events."

RADICALS-HD was conducted in the U.K., Canada, Denmark, and Ireland, and included 2,839 men who were randomly assigned to either 24 months of ADT, 6 months of ADT, or no ADT. The investigators compared radiation alone versus short-course ADT in 1,480 men; and long-course ADT versus short-course ADT in 1,523 men.

These patients had a median age of 66 years. About a quarter of patients had stage pT3b/T4 cancer, and 20% had a Gleason score of 8-10. Mean PSA before beginning radiotherapy was 0.22 ng/mL.

In comparing long- and short-term ADT, Parker reported long-term therapy improved time to salvage hormone therapy, with 10-year event-free rates of 75% versus 69% (HR 0.73, 95% CI 0.59-0.91), and freedom-from-distant metastases, with 10-year rates of 88% and 81%, respectively (HR 0.63, 95% 0.47-0.85).

However, there was no significant difference in overall survival (OS) between those two courses of therapy, with 10-year rates of 85% and 82% in the long- and short-term ADT cohorts.

In the case of the short-term versus no ADT comparison, there was no significant difference in freedom-from-distant metastases (10-year rates of 90% and 88%) or OS (10-year rates of 85% and 86%). However, there was an improvement with short-term ADT in terms of time to salvage hormone therapy, with a 9% absolute difference at 10 years (82% vs 73%; HR 0.54, 95% CI 0.42-0.70).

These results were consistent across all specified subgroups, Parker said.

  • author['full_name']

    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

The study was funded by Cancer Research U.K., Medical Research Council, and the National Institute for Health and Care Research's Clinical Research Network.

Parker reported relationships with Bayer, Janssen, Myovant, ITM, and AAA.

Gillessen reported relationships with Amgen, MSD, Svizzera Italiana, the Swiss Group for Clinical Cancer Research, the Swiss Academy of Multidisciplinary Oncology, AstraZeneca, Astellas, Bayer, Bristol Myers Squibb, Modra Pharmaceuticals, Myriad Genetics, Novartis, Orion, Pfizer, Roche, Telix, and Silvio Grasso Consulting.

Primary Source

European Society for Medical Oncology

Parker CC, et al "Duration of androgen deprivation therapy (ADT) with post-operative radiotherapy (RT) for prostate cancer: First results of the RADICALS-HD trial" ESMO 2022; Abstract LBA9.