Researchers from the Trans-Tasman Radiation Oncology Group 96.01 trial study (TROG 96.01) concluded that six months of treatment with neoadjuvant androgen deprivation combined with radiation reduced the risk for disease-specific death by 49% in men with locally advanced prostate cancer.
During the period of June 1996 to February 2000, 818 men with T2b, T2c, T3 and T4 N0 M0 prostate cancers randomly receive radiotherapy alone (n=270), 3-month neoadjuvant androgen deprivation therapy (ADT) plus radiotherapy (n=265) or 6-month neoadjuvant ADT plus radiotherapy (n=267). All the men were aged from 41 to 87 years
The men in the experimental arms were assigned to neoadjuvant ADT with once-monthly subcutaneous 3.6 mg goserelin (Zoladex) and thrice-daily oral 250 mg flutamide (Eulexin). Therapy began 2 months before radiation in the 3-month group and 5 months before radiation in the 6-month group.
All men in the trial received 66 Gy of radiotherapy.
During the course of the study there were 334 deaths of which 159 were due to prostate cancer:
1- Disease-specific mortality was 22% in the radiotherapy group vs. 18.9% for the 3-month group (HR=0.86; 95% CI, 0.6-1.23) and 11.4% in the 6-month group (HR=0.49; 95% CI, 0.32-0.74).
2- Researchers said patients had better disease-specific mortality with 6-month neoadjuvant ADT compared with radiotherapy in all subgroups; however, results were inconclusive for those with clinical stage T2b, initial PSA of at least 20 mcg/L or intermediate-risk tumors.
3- Ten-year all-cause mortality was 42.5% in the radiotherapy group, 36.7% in the 3-month group (HR=0.84; 95% CI, 0.65-1.08) and 29.2% in the 36-month group (HR=0.63; 95% CI, 0.48-0.83).
4- Cumulative incidence of non-prostate cancer mortality at 10 years was similar between the three groups.
According to Chris Parker, MD, consultant clinical oncologist with the Royal Marsden Hospital, United Kingdom, where the study was performed, these results show a clear advantage for neoadjuvant ADT compared with radiotherapy dose escalation because neoadjuvant ADT appears to cut the risk by half for prostate cancer death, whereas radiotherapy dose escalation has not yet been shown to affect mortality. He also said that the toxicities associated with 6-month neoadjuvant ADT were temporary, whereas radiotherapy dose escalation increases the risk for permanent sequelae.
Parker went on to say that TROG 96.01 is an important trial that has two clear messages for current clinical practice:
1- “First, it confirms that neoadjuvant ADT significantly reduces mortality after radiotherapy for high-risk prostate cancer and is a standard of care.
2- It helps to resolve the uncertainty regarding neoadjuvant ADT duration and strongly suggests that men receiving neoadjuvant ADT should have at least 6 months of treatment.”
Joel T Nowak, M.A., M.S.W.