Dose escalation above 70Gy has been analysed by Viani et al,r a meta analysis of 7 RCT’s (n=2812), a comparative effectiveness study by Kalbasi et alr of 5 RCTs (High Risk patients n=13,538) a database analysis by Hall et alr (n=20,028) and Ph III trial by Kuban et al (2011).r Viani et alr found a significant reduction in the incidence of biochemical failure in patients with low, intermediate and high risk localised prostate cancer 24.8% with high dose RT (HDRT) vs 34.6% with conventional dose RT (CDRT) (p < 0.0001) (see graph below). There was no difference in mortality rate and specific prostate cancer mortality rates between CDRT and HDRT. On subgroup analysis, all subgroups showed a linear correlation between total dose of radiotherapy and biochemical failure. The analysis by Kalbasi et alr found that dose escalated EBRT (> 75.6Gy) was associated with improved overall survival for patients with high risk prostate cancer (HR 0.84, 95% CI, 0.80 - 0.88; p < 0.001) and that for every incremental increase of about 2Gy in dose, there was a 7.8% (95% CI, 5.4 - 10.2%; p < 0.001) reduction in the hazard of death for intermediate risk patients.
© Int J Radiat Biol Phys 2009 Vianir
Use of Androgen Deprivation Therapy
Bolla et al (2016)/EORTC 22991r randomised 819 patients with intermediate and high risk prostate cancer to RT alone or RT + ADT. The RT doses were either 70Gy, 74Gy or 78 Gy and ADT was given during and following RT. 75% of patients had intermediate risk disease and and 25% high risk. After a median follow up of 7.2 years, After a median follow-up of 7.2 years RT+ ADT improved Biochemical PFS compared to RT alone (HR=0.53, CI: 0.42-0.67, P<0.001) irrespective of the radiation dose. Clinical PFS was also statistically significantly improved 80.8% for RT alone vs 88.7% for RT+ADT (HR=0.63, 95% CI: 0.48-0.84, P=0.001) .
The addition of short term ADT to dose escalated (>70 Gy) radiotherapy may be considered. However, the risk of adverse effects versus the potential benefit should be discussed with patients prior to treatment.
Multiple randomised trials have demonstrated an improvement in disease outcomes when short term ADT (3-8 months) was given in addition to radiotherapy.
- In RTOG 9408, 1979 patients were randomly assigned to radiotherapy (66.6Gy) with or without ADT (6 months in total, commencing 2 months before radiotherapy). At a median follow up of 9.1 years there was a benefit for short term ADT and radiotherapy in 10 year overall survival (62% vs. 57%, P =0.03) and disease specific mortality (8% vs. 4%, p =0.001).r
- Other randomised trials have also shown a benefit in terms of overall survivalr and freedom from failure.rr
- D'Amicor published a small study of 100 patients reporting that intermediate risk patients randomised to conformal lower dose RT + 6 months ADT had a significantly better survival and lower prostate cancer specific mortality when compared to RT alone. 8 year survival rates were 74% (95% CI 64-82%) vs 61% (95 CI, 49-71%) for RT + ADT and RT alone. Approximately 75% of patients in this study had intermediate risk disease.