Patient advocates have long raised the question about the wisdom in using hormone therapy for extended periods of time. The introduction of intermittent scheduling of hormone therapy (ADT) has become more acceptable thanks to the questions raised by the community and the support of some oncologists who have been willing to think out of the box.
In many circles, the discussion on ADT has turned to a conversation that can be characterized as the reckless use of ADT to control PSA, a tumor marker lacking in sensitivity. Some doctors are now saying that the over use of ADT has actually lead to the development of a new disease, hormone refractory non-metastatic prostate cancer. For those men who have developed this “new” disease it can be argued that they have been unnecessarily denied the actual benefits of ADT
We often say that the goal of prostate cancer treatment is turn it into a chronic disease. Our aggressive use of the PSA marker has pushed back the time of diagnosis of the disease by at least 10 years. Deferred treatment studies such as the EORTC study ( Studer et al. J Clin Oncol, 2006) are scheduled to be updated in 2011 when the follow up will be 13 years and 80% of the study population will have died. This will provide us with an increased perspective of a further 10 years.
Prostate cancer, a disease with a possible course of 20 years without active intervention, should hint to us that there are alternate management possibilities, possibly including less aggressive including intermittent schedules of ADT. In the ideal world, individual management of advanced prostate cancer should be the goal, with ADT schedules being flexible and directly responsive to the individual’s specific medical situation.
Adding to the fire, the ongoing Scandinavian surgical trial continues to show only a modest benefit for active surgical treatment over watchful waiting. However, even as we approach 15 years of follow up, the non-radically treated group has not yet separated away from the treated group and continues to run parallel lines similar to those of a decade ago. Additionally, the findings from the intergroup study, ( Warde et al. J Clin Oncol, 2010) which followed on the findings that hormones were necessary for optimal utilization of radiation therapy, have shown only a modest 10% benefit in survival at 7 years compared to the combination treated group,R/T + ADT versus ADT alone.
Coupling this information with our knowledge of the significant complications of prolonged ADT, we need to be rational and question the willy-nilly use of long term ADT. Reviews have shown that a short course, even just 6 months, was as efficient as 3 years hormone therapy.
ADT might better be held back until they can provide the maximum benefit without also causing additional harm. This might well be in late stage disease instead of as early stages as we now using it. In situation where short term ADT can benefit radiation short term ADT has a place
As drug development progresses we have an increasing number of alternative treatments that do work, maybe even more effectively with early disease. Given the age of many men and likely co-morbidity that ADT will cause (and of course the quality of life issues) perhaps we need to re-think the sequencing of treatments, holding ADT for a later stage and using intermittent treatment on a regular basis instead of continuous treatment.
Peter Whelan, FRCS as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc… of their research by referencing the published abstract.
Joel T Nowak, M.A., M.S.W.