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ADT after RT - Hormone treatment after radiation


JimJimJimJim

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It is now well accepted that hormone treatment (Androgen Deprivation Therapy, or ADT) added to radiation works better than radiation alone.

But the questions each man and his doctor must answer:

  1. Which basic hormone treatment (like the LHRH agonist 'Zoladex') is best?
  2. How long should it be continued for best result?
  3. Should a second hormone treatment - anti-androgens like 'Cosudex' - be taken at the same time?

For almost 3 years now I have, every few months, scoured the internet for papers that will give me further information on these questions so I can check that I am still doing the best I can.

Now a team led by Sasse has applied their professional effort to answering these questions.

And the answers seem to be that the evidence shows:

  1. Zoladex
  2. Three years
  3. No anti-androgen

How strong are these conclusions?

Zoladex (Goserelin)

The evidence is good – adding it to radiation does lead to longer life, fewer prostate cancer deaths. But it just so happened that the best done studies happened to use Zoladex.

The reviewers state that there is no reason to expect there would not be the same result with other LHRH agonists - like Lupron (leuprorelin), Eligard (leuprolide), Lucrin (leuprorelin acetate), Suprefact (buserelin), Suprecor (buserelin), Synarel (nafarelin), histrelin (Supprelin), Suprelorin (deslorelin), Ovuplant(deslorelin), Triptorelin.

Three years

The longest hormone treatment studied was for 3 years, and this resulted in longer survival, and fewer deaths by prostate cancer, than any lesser period. (In other papers the difference between 2 years of hormone treatment after RT and 3 years of hormone treatment after RT has been called "modest".)

Adding an anti-androgen

Complete hormonal blockade was not shown in the studies in this review to be superior to goserelin monotherapy. That is – no study showed that Zoladex + Cosudex was better Zoladex by itself, after radiation.

This is no surprise, seeing the studies reported here with Zoladex + Cosudex used hormone treatment for 6 months or less.

In a study which compared survival using Zoladex + Cosudex with Zoladex alone (no radiation for either), Akaza produced a survival graph. The graph shows no difference at all in survival for about the first two years. But by year 6, 75% of the men were alive in the combined hormone group, compared to 60% in the single hormone group. More, the trend of the single hormone group curve after year 6 was continuing downwards more steeply. Others have speculated, based on this and other studies, a much greater difference after 10 years.

So the fact that the studies in this review found no difference in adding Cosudex after 6 months does not mean that there may be a significant difference if the addition of Cosudex had been continued for some years.

Why didn't my doctor do this?

  • Some of the studies are quite recent. The 3 year study (by Bolla et al.), for instance, was reported in 2010.
  • Your doctor knows your health. Your doctor may know, for instance, that although they have reported all OK to you because everything is in the normal range, your blood tests may be at the low end of the normal range in, say, liver function or sugar. A judgement may have be made that the extra pressure of these strong hormone medications should be limited for your safety.
  • Even if you are in the best health, many doctors give hormone treatment intermittently – some time on, and some time off. For instance a medical oncologist with a world-wide reputation, Dr Snuffy Myers, reports that he seldom gives hormone treatment for more than one year at a time (except when he is observing a 2 year protocol after primary radiation treatment).
  • You may have not have had the anti-androgen Cosudex added to your treatment because your primary hormone treatment was going to be 2 years or less. Cosudex may need more than 2 years to make a difference.
  • Cost may be a factor as well. Cosudex is not covered under PBS in Australia unless you have metastatic disease.
  • Your cancer took its biggest hit from the radiation. It took its next biggest hit from the primary LHRH agonist like Zoladex and the effect of extra time taking that diminishes. The difference between 2 and 3 years on Zoladex has been described as "modest". The effect of adding Cosudex has also been described as "modest".
  • Your cancer may not be locally advanced (grown through the prostate wall). The studies chosen had to include locally advanced cancers.

If you can't find the full papers by Sasse et al., by Akaza, or by Bolla et al., contact Jim Marshall and he will send you a copy.

BMC Cancer. 2012 Feb 2;12:54.

Androgenic suppression combined with radiotherapy for the treatment of prostate adenocarcinoma: a systematic review.

Sasse AD, Sasse E, Carvalho AM, Macedo LT.

Source

Center for Evidences in Oncology, Clinical Oncology Service, Internal Medicine Department Faculty of Medical Sciences, University of Campinas--UNICAMP, 6111, 13083-970 Campinas, SP, Brazil. sasse@cevon.com.br.

Abstract

ABSTRACT:

BACKGROUND:

Locally advanced prostate cancer is often associated with elevated recurrence rates. Despite the modest response observed, external-beam radiotherapy has been the preferred treatment for this condition. More recent evidence from randomised trials has demonstrated clinical benefit with the combined use of androgen suppression in such cases. The aim of this meta-analysis is to compare the combination of distinct hormone therapy modalities versus radiotherapy alone for overall survival, disease-free survival and toxicity.

METHODS:

Databases (MEDLINE, EMBASE, LILACS, Cochrane databases and ClinicalTrials.gov) were scanned for randomised clinical trials involving radiotherapy with or without androgen suppression in local prostate cancer. The search strategy included articles published until October 2011. The studies were examined and the data of interest were plotted for meta-analysis. Survival outcomes were reported as a hazard ratio with corresponding 95% confidence intervals.

RESULTS:

Data from ten trials published from 1988 to 2011 were included, comprising 6555 patients. There was a statistically significant advantage to the use of androgen suppression, in terms of both overall survival and disease free survival, when compared to radiotherapy alone. The use of long-term goserelin (up to three years) was the strategy providing the higher magnitude of clinical benefit. In contrast to goserelin, there were no trials evaluating the use of other luteinizing hormone-releasing hormone (LHRH) analogues as monotherapy. Complete hormonal blockade was not shown to be superior to goserelin monotherapy.

CONCLUSIONS:

Based on the findings of this systematic review, the evidence supports the use of androgen suppression with goserelin monotherapy as the standard treatment for patients with prostate cancer treated with radiotherapy, which are at high risk of recurrence or metastases.

PMID: 22299707

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, FREE in this case).

Any highlighting (except the title) is not by the author, but by Jim Marshall.Jim is not a doctor.

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