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ORLANDO -- Low-dose brachytherapy boosts held prostate cancer in check significantly better than dose-escalated external-beam radiation therapy (EBRT) in men with unfavorable-risk disease, a randomized trial showed.

Patients treated with brachytherapy after androgen deprivation therapy (ADT) and whole-pelvis EBRT had an estimated 9-year relapse-free survival (RFS) of 83% compared with 63% for patients who received a conformal EBRT boost. The difference in favor of brachytherapy emerged after 5 years of follow-up, , of the British Columbia Cancer Agency in Vancouver, reported here at the Genitourinary Cancers Symposium.

"In the context of 12 months of androgen deprivation therapy and whole pelvis external beam radiotherapy, treatment with a low-dose pelvic brachytherapy boost results in a 50% reduction in biochemical relapse compared to dose-escalated EBRT to 78 Gray," Tyldesley said. "At 6.5 years of follow-up, there was no difference in overall survival, prostate cancer specific survival, or metastasis-free survival."

However, "there was increased late grade 3 or higher GU toxicity with the low-dose rate boost, a 5% to 6% increase in the prevalence of late GU toxicity," he said.

The findings came from a randomized trial involving 398 patients with high-risk localized prostate cancer. All patients received 12 months of ADT and EBRT (46 Gy in 23 fractions) and were randomized to the low-dose iodine-125 brachytherapy boost to the prostate or an EBRT boost (32 Gy in 16 fractions).

The primary endpoint was RFS. The two treatment arms had identical 94% RFS at 3 years. Thereafter, the brachytherapy arm demonstrated significantly better RFS: 89% versus 77% at 5 years, 86% versus 71% at 7 years, and 83% versus 63% at 9 years (HR 0.473, P=0.0022).

Assessment of late (6 years) toxicity showed that 95% of patients in both arms were free of late gastrointestinal toxicity, 90% of patients in the EBRT arm were free of late genitourinary (GU) toxicity, and 80% of patients in the brachytherapy arm were free of late GU toxicity.

No Survival Benefit With Third-, Fourth-line Cabozantinib

Patients with metastatic castration-resistant prostate cancer (mCRPC) got no survival benefit from the small-molecule inhibitor cabozantinib (Cometriq) used as third- or fourth-line therapy, a randomized trial showed.

Patients treated with cabozantinib had a median overall survival (OS) of 11.0 months versus 9.8 months with prednisone. Median progression-free survival (PFS) in the cabozantinib arm was twice that of the prednisone control group.

"Subgroup analyses suggested a larger improvement in overall survival in men with visceral metastases or who had received prior cabazitaxel," said , of Massachusetts General Hospital Cancer Center in Boston. "Cabozantinib was associated with significant improvements in bone-scan response, progression-free survival, time to first skeletal-related event, circulating tumor cell conversion, and bone biomarkers."

Smith reported final results from the phase II, randomized trial involving patients with mCRPC and progression during or after treatment with docetaxel and abiraterone (Zytiga) and/or enzalutamide (Xtandi). The patients were randomized 2:1 to cabozantinib or prednisone and followed until disease progression. The primary endpoint was OS.

Data analysis included 1,028 patients. The primary analysis showed no significant difference between treatment groups (HR 0.90, P=0.213). PFS in the cabozantinib arm was double that of the prednisone group (5.6 versus 2.8 months, P<0.001).

The cabozantinib group had a significantly higher rate of bone scan response (42% versus 3%, P<0.001), and the duration of bone response was 5.8 months versus 1.8 months in favor of cabozantinib. The time to first SRE also favored cabozantinib (139 events versus 190, P<0.001).

RT Plus Brief ADT Equals Better Control

A 6-month course of ADT added to radiation therapy led to significantly better biochemical relapse-free (BRFS) and disease-free survival (DFS) than did irradiation alone for intermediate-risk prostate cancer, results of a phase III trial showed.

Patients who received ADT plus EBRT total dose of 78 Gy had a 5-year biochemical failure rate of 2.4% compared with 13.2% for patients who received EBRT alone. ADT plus a 70-Gy dose of EBRT had a 5-year failure rate of 7.8%. Failure rates at 10 years were 34.5% with EBRT alone, 16.6% with ADT and 78 Gy EBRT, and 23.4% for ADT plus 70 Gy EBRT.

Similar advantages emerged for ADT plus EBRT with respect to DFS. The 5-year DFS was 97.6% for ADT-78 Gy EBRT, 93.1% for ADT-70 Gy EBRT, and 86.3% for 78 Gy EBRT alone. The 10-year DFS was 89.8%, 77.2%, and 64.7%, for the two ADT arms and EBRT alone, respectively.

"In intermediate-risk prostate cancer, the use of short-term androgen deprivation therapy in association with prostate radiotherapy, even at lower doses, leads to a superior biochemical control and disease-free survival as compared to dose-escalated prostate radiotherapy alone," said , of Sherbrooke University Hospital Center in Canada.

Nabid reported data from a phase III, multicenter, randomized trial involving patients with newly diagnosed intermediate-risk prostate cancer: T 1-2, Gleason score ≤7, and PSA 10 to 20 ng/L. The patients were randomized to one of the three treatment strategies, and the primary endpoints were freedom from biochemical relapse and DFS.

Results after a median follow-up of 75.4 months showed clear advantages for short-course ADT plus EBRT versus EBRT alone. For biochemical failure, the 5-year results showed that the combination of 78 Gy EBRT and ADT outperformed EBRT alone (P<0.001) and the 70 Gy EBRT-ADT combination (P=0.027), and the 70 Gy EBRT-ADT arm also prevented relapse significantly better than did EBRT alone (P=0.043).

At 10 years, 78 Gy EBRT-ADT remained significantly better than EBRT alone (P<0.001) and compared with 70 Gy EBRT-ADT (P=0.021).

For DFS, both of the combination arms outperformed EBRT alone at 5 years (P<0.001, P<0.017), and the 78 Gy EBRT-ADT arm outperformed the other combination arm (P=0.043). At 10 years, DFS remained significantly higher for the combination arms (P<0.001, P=0.017) versus EBRT alone.

The findings extend previously reported data from the same center, showing that ADT plus EBRT outperforms EBRT alone in patients with high-risk localized prostate cancer. Consistent with the results in high-risk patients, the combination did not significantly improve OS.