- 1 Are cumulative treatment toxicities different when androgen blockade (androgen ablation, deprivation) is used as first line therapy in the adjuvant or neoadjuvant setting with radiotherapy for locally advanced prostate cancer in locally advanced disease?
- 2 Evidence summary and recommendations
- 3 References
- 4 Appendices
Are cumulative treatment toxicities different when androgen blockade (androgen ablation, deprivation) is used as first line therapy in the adjuvant or neoadjuvant setting with radiotherapy for locally advanced prostate cancer in locally advanced disease?
The effect of long-term androgen deprivation on radiotherapy toxicities
Two RCTs assessing long-term androgen deprivation therapy in addition to radiotherapy report radiotherapy toxicity outcomes. The first trial is a comparison of XRT alone versus radiotherapy with three years of LHRH agonist. This trial used whole pelvis radiotherapy. The second trial is a comparison of radiotherapy alone versus radiotherapy with two to five years of a non–steroidal anti– androgen, bicalutamide. No details regarding radiotherapy are available for this trial.
An increase in urinary incontinence (16 versus 29%, p=0.002) with the addition of androgen deprivation therapy was reported in one trial.No increase in acute urinary or bowel toxicity or other late toxicity was reported in this trial. While there was no apparent increase in urinary or bowel toxicity in the second trialthey were not assessed for statistical significance.
A recent update of RTOG 85-31 which compared radiotherapy alone with radiotherapy plus indefinite adjuvant androgen blockade also reported no statistically significantly difference in RTOG grade 3–4 genitourinary or gastrointestinal toxicities.
The effect of short-term androgen deprivation on radiotherapy toxicities
Three RCTs assessing short-term ADT in addition to radiotherapy report radiotherapy toxicity outcomes. The first trial, TROG 96-01, is a comparison of radiotherapy alone versus three months and six months of neoadjuvant ADT.  The second trial, RTOG 86-01, is a comparison of radiotherapy alone versus radiotherapy with three months of ADT. Whole pelvis radiotherapy was used. The third trial is a comparison of radiotherapy alone versus radiotherapy with six months of ADT. In all trials ADT consisted of an LHRH agonist and a non-steroidal anti-androgen, flutamide. All trials were consistent, with no increase in acute or late urinary or bowel toxicity reported with the addition of androgen blockade.
A fourth trial, RTOG 83-07, compared Megestrol versus Diethylstilbestrol. These drugs would not be routinely used as first-line therapy and as such this trial was not considered further.
The effect of short-term versus long-term androgen deprivation on radiotherapy toxicities
One RCT, RTOG 92-02, compared short-term with long-term androgen deprivation (four months neoadjuvant plus concurrent LHRH agonist and non-steroidal anti-androgen, flutamide, with or without two years of adjuvant LHRH agonist). This trial used whole pelvis radiotherapy. A statistically significant increase in late RTOG gastrointestinal toxicity grade 3–5 was reported with long-term ADT although absolute rates were low (3 versus 1%, p=0.04) and grade 4 or 5 toxicities were less than 1%. Accounting for differences in reporting of toxicity the evidence suggests that there is no significant increase in radiotherapy toxicity with the addition of ADT. It should be noted that sexual function is inadequately assessed in these studies. Only one trial has reported an increase in late impotence with six months of androgen deprivation.
Evidence summary and recommendations
|There does not appear to be any difference in radiotherapy toxicities (urinary and gastrointestinal) with the addition of androgen deprivation therapy to radiotherapy, although it is acknowledged that sexual function has been inadequately assessed in these studies.||II||, , , , , , , , |
|Androgen deprivation therapy can be used in combination with radiotherapy without additional radiotherapy toxicities (urinary and gastrointestinal). Effect on sexual functioning has not been defined.||C|
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