In this presented study, all men had clinical stage T1-3a disease by digital rectal examination. PSA had to be lower than 100 ng/ml, and all were diagnosed with adenocarcinoma of the prostate, without any radiographic evidence of metastasis. Furthermore, all men had either a biopsy Gleason score of 8-10 or a Kattan preoperative nomogram probability of <60% biochemical progression-free survival at five years after radical prostatectomy.
The study design is shown in figure 1. The primary endpoint of the study was designed to have an 89% power (with one-sided type 1 error rate of 0.025) to detect an almost 12% difference between the two groups. It was assumed that the rate of 3-year biochemical progression-free survival is 57% (in the standard arm) and 69.1% in the experimental arm. The sample size included 750 patients, with 375 randomized to each arm. Secondary endpoints included overall biochemical progression-free survival, freedom from treatment failure, and overall survival.
The PSA was checked every three months for 36 months, then every six months for 36 months, and then annually. BCR was defined as a PSA above 0.2 ng/ml on two consecutive occasions at least three months apart. The time of BCR was measured from randomization to the date of the first PSA rise above 0.2 ng/ml. The patient baseline characteristics in both arms are shown in table 1. The adverse events in the chemotherapy arm are described in table 2 and the summary of outcomes are shown in table 3. It is noteworthy, that approximately 40% of the men received salvage radiation therapy, ADT, or both, before meeting the definition of BCR.
The biochemical progression-free survival is shown in figure 1, demonstrating an advantage in the neoadjuvant arm after three, five, and eight years of follow-up. Freedom from treatment failure is shown in figure 2, again showing an advantage to the neoadjuvant arm, and lastly, figure 3 demonstrates the overall survival rate in both treatment arms.
Table 1- Patient baseline characteristics:
Table 2 – Adverse events in the chemotherapy arm:
Table 3 – Summary of trial outcomes:
Figure 1- Biochemical progression-free survival:
Figure 2 - Freedom from treatment failure:
Figure 3 – Overall survival rate:
Dr. Eastham concluded his talk and summarized the study’s main findings. There was a statistically significant improvement in biochemical progression-free survival throughout the study, in the neoadjuvant arm. There is strong evidence for a survival benefit stemming from the neoadjuvant chemohormonal therapy. These data support the use of neoadjuvant chemohormonal therapy before radical prostatectomy, as a standard option, for at least delaying biochemical progression-free survival, in men with clinically localized high-risk prostate cancer. Currently, work is being done to examine the genomic signatures that correlate with clinical improvement. Metastasis-free survival data was not presented and will be reported in the future and correlated with the overall survival data.
Presented by: James Eastham, MD, Memorial Sloan Kettering Cancer Center
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the American Urological Association's 2019 Annual Meeting (AUA 2019), May 3 – 6, 2019 in Chicago, Illinois