Conformal technique dose escalation in prostate cancer: improved cancer control with higher doses in patients with pretreatment PSA ≥ 10 ngm/ml

Purpose: Single institutions and an NCI supported group of institutions have been investigating the value of dose escalation in patients with prostate cancer treated by conformal treatment techniques. Improvement in morbidity has been previously established, while this report identifies the pretreatment PSA level subgroups of patients who benefitted in cancer control from higher dose. Materials and Methods: We report actuarial bNED survival rates for 375 consecutive patients with known pretreatment PSA levels treated with conformal technique between 5/89 and 12/93. The whole pelvis was treated to 45 Gy in 25 fractions in all T2C,3, all Gleason 8, 9, 10 and all patients with pretreatment PSA ≥20. The prostate ± seminal vesicles was boosted at 2.1 Gy/day to the center of the prostate to 65-79 Gy (65-69 N=50), 70-72.49 N=94, 72.5-74.9 N=82, 75-77.49 N=129 and ≥77.5 N=20). The median followup is 21 mos with a range of 3 to 67 mos. The highest dose patients have the least followup, reducing the impact of the highest dose levels at this time. Patients are analyzed for the entire group divided at 71 Gy and at 73 Gy calculated at the center of the prostate. Each dose group is then subdivided by pretreatment PSA levels <10, 10-19.9, and ≥20 ngm/ml and dose levels are compared within pretreatment PSA level group. bNED failure is defined as PSA ≥1.5 ngm/ml and rising on two consecutive values. Results: Table 1 shows the bNED survival rates at 24 and 36 mos for all patients and the three pretreatment PSA level groups. For all patients pooled, there is an overall advantage to using doses ≥71 Gy (64% vs 85% at 36 mo, p=.006) and ≥73 Gy (71% vs 86% at 36 mo, p=.07). The subgroup of PSA <10 ngm/ml, however, shows no benefit in bNED survival when using doses over 71 Gy (90% vs 93% at 36 mo) or 73 Gy (91 vs 94% at 36 mo). The subgroup PSA 10 ngm/ml to 19.9 ngm/ml shows improved cancer control when using doses over 71 Gy (61% vs 88% at 36 mo, p=.03) and over 73 Gy at 24 mos (75% vs 92%, p=.05). The subgroup PSA ≥20 ngm/ml shows improved cancer control over 71 Gy (18% vs 67% at 36 mo, p=.003) and 73 Gy (42% vs 69% at 24 mo, p=.02). The median and mean time to failure for the 18 failures in the 10-19.9 ngm/ml group is 14.3 mos and 18.2 mos (range 3.1-46.8 mos) and for the 33 failures in the ≥20 ngm/ml group 14.5 mos and 13.9 mos (range 2.1-46.0 mos). Conclusions: 1) Patients with pretreatment PSA levels of <10 ngm/ml do not benefit from dose escalation beyond 71 Gy evaluated at 3 yrs. 2) Patients with pretreatment PSA levels of >10 ngm/ml do benefit from dose escalation above 71 and 73 Gy evaluated at 3 yrs. 3) Multimodal treatment of high PSA patients should include irradiating the center of prostate irradiation to dose levels above 71-73 Gy. 4) Longer followup will clarify the effects of dose >75 Gy and show the changes that occur in these results with time. 5) Clinical trials of dose escalation in prostate cancer are validated