Peep Supports High-Dose RT, Lengthy-Term ADT as Ordinary for High-Probability Prostate Most cancers

— OS, PFS, cancer-explicit survival all improved, with out a make higher in toxicity

Charles Bankhead, Senior Editor, MedPage Right this moment

SAN FRANCISCO — Men with high-bother localized prostate cancer lived vastly longer with dose-escalated radiation therapy (RT) plus long-term androgen deprivation therapy (ADT), constant with long-term notice-up from a randomized trial.

After a median notice-up of 9.5 years, the ten-year overall survival (OS) price increased from 65.9% with traditional-dose (70 Gy) RT plus 3 years of ADT to 77% with 80 Gy RT. Most cancers-explicit survival (CSS) and progression-free survival (PFS) at 10 years additionally improved vastly with the higher dose of RT.

Unhurried-occurring genitourinary (GU) and gastrointestinal (GI) toxicity did not make higher with the higher RT dose, and quality of lifestyles used to be same between cure groups, reported Christophe Hennequin, MD, PhD, of Saint-Louis Sanatorium in Paris, on the Genitourinary Cancers Symposium.

“Even when we utilize long-term ADT, high-dose RT improved progression-free survival, cancer-explicit survival, and overall survival in high-bother prostate cancer without rising toxicity,” acknowledged Hennequin. “On the alternative hand, IMRT [intensity-modulated RT] is required to procure these results.”

“We now enjoy level-one proof that high-dose RT with long-term ADT must be a conventional of care in high-bother prostate cancer,” he added.

Gathering Details

The findings, from the French Genito-Urinary Tumor Neighborhood (GETUG) 18, added to and prolonged existing proof that high-dose RT plus long-term ADT yields greater outcomes for prime-bother prostate cancer. RT and ADT enjoy biologic synergy and co-dependent, advanced cytotoxic interactions. Finding the merely RT dose to carry out the one outcomes has been a foremost topic, constant with invited discussant Neha Vapiwala, MD, of Penn Tablets in Philadelphia.

Quite loads of stories evaluated long- versus short-course ADT with an RT dose of 70 Gy. In traditional, long-term ADT done greater or non-homely OS.

The Length of Androgen-Deprivation Therapy (DART) trial pushed the envelope a minute of further, comparing 4 versus 28 months of ADT and dose-escalated RT ranging between 76 and 82 Gy. Vapiwala pointed out that the DART inhabitants used to be not purely high bother, but a mixture of intermediate- and high-bother prostate cancer.

Nonetheless, the foremost diagnosis showed greater 5-year OS with long-term ADT, no make higher in gradual RT toxicity, but a foremost make higher in nonfatal cardiovascular events. Additionally, short-course ADT used to be connected to a higher price of unknown-cause deaths.

“Some enjoy postulated that the OS profit will were a mirrored image of an strangely higher quantity of deaths in the non permanent ADT arm that were connected to reasonably a few causes,” acknowledged Vapiwala.

By 10 years, the OS profit no longer remained statistically foremost. Nonetheless, the effects showed a “clinically relevant” 11.5% absolute distinction in prefer of the long-term ADT. The make higher in cardiovascular events viewed at 5 years no longer existed.

“This argues that in the environment of dose-escalated radiation therapy, long-term ADT is clearly traditional,” acknowledged Vapiwala.

The findings additionally led to the question of whether ADT can catch up on higher-dose RT. Can the advantages seen in high-bother sufferers be maintained with a lower dose of RT?

“That is the build the work that used to be presented this present day [GETUG-18] the truth is helps us see totally on the contribution of the dose escalation of radiation in the context of long-term androgen deprivation therapy, taking that because the de facto traditional for prime-bother sufferers,” acknowledged Vapiwala. “This used to be a high-bother inhabitants, as 83% of the sufferers got pelvic nodal radiation or wanted to be proven to be pathologic N0 on dissection.”

“With a foremost endpoint of 5-year biochemical or scientific progression-free survival, you saw that not only are these [Kaplan-Meier] curves statistically vastly separated, but they remained so over the final duration of the notice-up. Even per chance extra excellent are the secondary endpoints of prostate cancer-explicit survival and overall survival, which were statistically vastly improved,” Vapiwala added.

Noting that the advantages were done with out a make higher in toxicity, Vapiwala acknowledged the effects are “put together asserting for quite a bit of, per chance put together changing for some, must you would possibly want to well perchance well maybe very successfully be not already offering this.”


GETUG 18 fervent 505 sufferers with high-bother localized prostate cancer enrolled at 25 French centers from June 2009 to January 2013. All sufferers got 3 years of ADT and were randomized to an 80- or 70-Gy dose of RT. Hennequin principal that vastly extra sufferers in the 80-Gy arm were handled by IMRT (80.6% vs 58.6%, P<0.001).

The foremost endpoint used to be 5-year PFS, which the 80-Gy cure arm met (91.4% vs 88.1%). Secondary endpoints included CSS, OS, and toxicity. The up as a lot as now diagnosis reported by Hennequin showed a 10-year PFS of 83.6% vs 72.2%, representing a 44% discount in the hazard for progression or dying (95% CI 0.40-0.76, P=0.0005).

The 10-year CSS used to be 95.6% with 80 Gy and 90.0% with 70 Gy, a 52% discount in the hazard ratio (95% CI 0.27-0.83, P=0.0090). The 11-point absolute distinction in 10-year OS translated valid into a 39% discount in the hazard (95% CI 0.44-0.85, P=0.0039).

The incidence of grade ≥2 and grade ≥3 GU toxicity used to be 19.9% and 3.2% in the 70-Gy arm and 20.6% and 2.0% in the sufferers who got 80 Gy RT. Unhurried-occurring grade ≥2 and grade ≥3 GI toxicity used to be 8.8% and 1.6% with 70 Gy RT versus 6.9% and 1.6% with 80 Gy.

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    Charles Bankhead is senior editor for oncology and additionally covers urology, dermatology, and ophthalmology. He joined MedPage Right this moment in 2007. Note


GETUG 18 used to be supported by the French National Most cancers Institute, the French National Most cancers League, and AstraZeneca.

Hennequin disclosed relationships with Astellas, Bayer, Ipsen, and AstraZeneca.

Vapiwala reported no relevant disclosures.

Famous Source

Genitourinary Cancers Symposium

Source Reference: Hennequin C, et al “Lengthy-term results of dose escalation (80 vs 70 Gy) mixed with long-term androgen deprivation therapy in high-bother prostate cancers: GETUG-AFU 18 randomized trial” GUCS 2024; Abstract LBA259.

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