Biochemical Failure in Intermediate Risk Prostate Cancer: Then What? Long-Term Data from a Phase III Trial.

Abstract

Aiming to determine long-term outcomes post biochemical failure (BF) in patients (pts) treated for intermediate-risk prostate cancer, we analyzed data from our prospective randomized trial (PCS III). From December 2000 to September 2010, 600 pts with intermediate risk prostate cancer (IRPC) received prostate radiotherapy (RT) with or without short-term (6 months) androgen deprivation therapy (ADT) on a Phase III trial. We report death rate from prostate cancer, rate and timing of BF plus the final clinical outcome of patients, alive or dead, with BF. Chi-squared test was used to compare BF and prostate cancer progression (PCP) rates between patient with or without ADT. Median age at randomization was 71 years (IQR 66-74). With a median follow-up (FU) of 13.5 years (IQR 11.2-17.0), 74.5% (447/600) were free from BF at last FU. Of these, 211 died, 79 stopped FU after 10 years, 9 were lost to FU, 6 withdrew from the study and 142 are still on FU, at a median follow-up of 13.2 years (IQR = 10.9 - 16.2). A total of 153 pts (25.5%) developed BF at a median time of 6.5 years post-randomization. Among BF pts, 82/153 died: we documented 32 deaths from prostate cancer (DPC) at a median time of 6 years post-BF and 50/153 pts died from other causes at a median time of 4.7 years from BF. 48/153 BF pts continue on FU: 34 show no clinical evidence of cancer, 9 developed a second cancer and 5 show clinical evidence of PCP. 20/153 pts stopped FU after 10 years: 3 of them with PCP. 3/153 pts were lost to FU: 1 after 3 years with prostate bone metastasis and 2 after 13 years of FU. In the first 5 years post-randomization, 47 pts (7.8%) presented BF with 1 (0.2%) DPC; between 6 and 10 years, there were another 84 (14%) BFs and 11 (1.8%) DPC. Finally, after 10 years and beyond, we recorded an additional 22 (3.7%) BFs and 20 (3.3%) DPC. The rate of patients who received ADT was significantly lower in patients with BF (74/153 = 48.4%) compared to patients without BF (324/447 = 72.5%), p<0.001. The rate of patients who received ADT was also significantly lower in patients with PCP (19/48 = 39.6%) compared to patients without PCP (379/552 = 68.7%), p<0.001. In our trial for intermediate-risk prostate cancer, a quarter of the pts developed BF. Most of the BFs occurred between 5- and 10- year post-randomization. Deaths due to prostate cancer post-BF occurred at a median time of 6 years, justifying the need for long-term FU. BF and PCP were significantly higher in patients not receiving ADT.