The most important piece of news today is the publication of the final result of the EORTC 30846 study comparing early and delayed hormone therapy. Other news includes:
- The hypothesis that fatty acid levels affect prostate cancer risk
- Prostate cancer risk based on a single PSA level
- Surgical treatment of men with T3-4 disease
- Early stage “vaccine” data in a rat model
The appropriate timing of hormone therapy for patients with prostate cancer is still controversial. After 13 years of follow-up, Schröder et al. have published the final report on EORTC 30846, a study designed to evaluate the relative benefits of early vs. delayed hormone therapy in 234 patients with lymph node-positive (pN1-3) cancer who did not receive local treatment of the primary tumor. The forms of hormone therapy used in their trial were either a depot luteinizing hormone-releasing hormone (LHRH) agonist and 1 month of an antiandrogen or surgical castration. The trial’s main objective was to show that delayed hormone therapy was not inferior to (i.e., was no worse than) immediate hormone therapy. Overall, 193 patients (82.5 percent) have died (97 on delayed ET and 96 on immediate ET), 59.4 percent as a result of prostate cancer. The median duration of treatment was 2.7 years in the delayed treatment group and 3.2 years in the immediate treatment group. Although the intention-to-treat analysis shows a 22 percent increase in the risk of death of those randomized to delayed treatment compared to those receiving immediate treatment, this difference is not statistically significant and so non-inferiority has not been proved. The median overall survival time on immediate therapy was 7.6 years versus 6.1 years in the delayed therapy group. The authors conclude that after 13 years of follow-up, both overall survival and prostate cancer-specific survival in the two groups appear similar, but the trial was underpowered to reach its goal of showing non-inferiority. On the other hand, The “New” prostate Cancer InfoLink would note that this is yet another trial that has shown a strong suggestion of an overall and a prostate cancer-specific survival benefit in favor of early treatment.
Park et al. at the University of Hawaii have investigated the hypothesis that levels of circulating fatty acids in the bloodstream may affect risk for prostate cancer. Specifically, they looked at the association between erythrocyte membrane fatty acid composition and prostate cancer risk using a group of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites (376 cases and 729 matched controls). They found no significant overall association for saturated, mono- and polyunsaturated fatty acid, or for specific n-3 and n-6 fatty acids, even when the analysis was limited to advanced or high grade prostate cancer. There was a positive association with palmitic acid in Japanese Americans compared to other groups. There was also an increased risk with n-3 fatty acids and the ratio of n-3/n-6 fatty acids in Whites. The authors conclude that although there was a suggestion of ethnicity-specific associations with some fatty acids, their overall findings do not support a role for fatty acids in prostate carcinogenesis.
Helzsouer et al. have attempted to further evaluate the association between a single serum PSA level and the subsequent development of prostate cancer. They measured PSA levels in 35 men who donated blood to a community-based serum bank in 1974 and who subsequently developed prostate cancer and in 35 matched controls from the same group of volunteers. PSA levels were higher in men who went on to develop prostate cancer, up to 6 years prior to the time of diagnosis. Interestingly, the PSA levels of all partricipants decreased with increasing time to diagnosis. The mean PSA level for the prostate cancer cases diagnosed within the first 3 years of follow-up was 16.2 ng/ml compared to 2.4 ng/ml for controls. By comparison, the mean PSA level for cancer cases diagnosed in years 4-6 following blood sampling was 9.6 ng/ml compared to 1.3 ng/ml for control. The sensitivity and the specificity of a PSA level ≥ 4 ng/ml up to 3 years prior to the time of clinical diagnosis were both 75 percent; up to 6 years prior to clinical diagnosis they were 67 and 85 percent, respectively. The authors conclude that, because PSA levels appear to be reasonably sensitive and specific in detecting prostate cancer up to 6 years prior to the time of usual diagnosis, their use in screening for the prevention of prostate cancer mortality should be evaluated in a controlled clinical trial.
In a review written in German, Palisaar and Noldus have summarized available data on the role of radical prostatectomy (RP) in patients initially diagnosed with locally advanced prostate cancer (or presumably also those patients found to have locally advanced prostate cancer after surgery has been initiated, even though localized disease was the original diagnosis). According to this review, overall survival rates of up to 86 percent can be achieved using RP as part of multimodal treatment in patients with T3-4N0M0 disease. The patients most likely to benefit from surgery include those with a biopsy Gleason score ≤ 8, a PSA level < 20 ng/ml, and cT3a cancer. Patients must be informed that additional treatment with radiotherapy and/or hormone therapy after surgery may be necessary (in 30-70 percent of such patients). Urinary incontinence may occur in up to 20 percent of patients, and severe incontinence (more than two pads per day) is observed in up to 6 percent. Adjuvant radiotherapy should be considered individually and is not routinely recommended. The authors conclude that cancer progression can possibly be delayed by surgical excision of the primary tumor, even in patients with metastasis, and state that the available data need to be checked in prospective randomized trials. (However, The “New” Prostate Cancer InfoLink suspects it would be very difficult to accrue patients to such trials today.)
Suckow et al. have published additional data on the potential of prostate cancer immunotherapeutic agents (“vaccines”) in the treatment of prostate cancer. Their data specifically addresses the use of a so-called “GFT vaccine” in a rat model of metastatic prostate cancer. It seems increasingly likely that (in time) we will see the development of a really effective series of prostate cancer immunotherapeutics. However, it may still be a while until we understand enough about the development of the disease to create such agents with ease.
Filed under: Diagnosis, Living with Prostate Cancer, Management, Treatment | Tagged: delayed, fat, immediate, PSA, risk, surgery, Treatment, vaccine |
THE "NEW" PROSTATE CANCER INFOLINK 
As usual Schröder introduces confusion … why would someone set out to prove a non-benefit for early treatment using an underpowered trial design?
Unfortunately, no definition of what the delay period was is given in the abstract. Still, I agree that this is another trial that supports early versus delayed hormonal treatment.
Ralph: I would remind you that this trial was planned in about 1993-4, at a time when the whole question of whether hormonal therapy did anything other than palliate pain in late stage disease was very much in question.
On that basis, 234 patients was more than double the number of patients enrolled in the ECOG 3886 trial, and it would have been perfectly reasonable to attempt to prove a non-benefit to hormone therapy. We now have 13 years of additional hindsight to draw on, and yet the value of early vs. delayed HT is still in question (probably because its value is limited to only some patients).