Goserelin

Neha Vapiwala, MD
Last Modified: February 25, 2007

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Question
My brother (nearly 58 years old) has prostate cancer, stage T1. Due to a recent arterial operation, surgery is not a great option for him. Radiation therapy is the doctor's recommendation. We would like to be informed further about this in the following manner:

  1. What are the extra risks, mainly to sexuality, impotence, and incontinence, owing to this additional treatment?
  2. What about PSA? Is this level after (during) radiation also an indicator for duration of the combined treatment, or for receiving 'Goserelin'?
  3. Is it possible for you to send us more information or documentation about this matter?


Answer
Neha Vapiwala, MD Senior Editor of OncoLink and Assistant Professor in the Department of Radiation Oncology at the Hospital of the University of Pennsylvania responds:

Thank you for your interest and question.

It has been observed and accepted that prostate cancer cells require androgens (i.e. testosterone, male hormone) to grow. This seems to be true to some degree, in that when you deprive a man with prostate cancer of androgens (androgen deprivation), the prostate tumors usually decrease in size. However, androgen deprivation alone will not kill off every last cancer cell. Thus, for curative treatment, androgen deprivation is used in addition to surgery or radiation, the latter serving as mechanisms to address the local bulk of disease.

For some background, the hypothalamus gland in the brain periodically releases a substance called luteinizing hormone-releasing hormone (LHRH). LHRH travels to special LHRH receptors that are located on the pituitary gland in the brain. Once LHRH fits into its receptors, it does what its name implies: LHRH triggers the pituitary gland to release luteinizing hormone (LH) on a cyclical basis. LH in turn periodically acts on the testicles to stimulate testosterone production. Goserelin acetate (brand name Zoladex) is a LH-releasing hormone (LHRH) agonist that mimics the body's natural (enodogenous) LHRH, except that it is present in the body on a constant basis, rather than on a periodic, cyclical basis like natural LHRH. This constant overstimulation of the pituitary gland by the LHRH-like goserelin causes the pituitary gland to counteract this overstimulation. It does so by decreasing the number of receptors that respond to LHRH (down-regulation). Reducing the quantity of LHRH receptors causes a resultant decrease in LH, and thus a decrease in testosterone. However, because goserelin is an agonist, there is an initial increase in LH and thus testosterone in the first 3 - 5 days. Thus, an anti-androgen drug such as bicalutamide or flutamide should be used during the initial week or two of goserelin therapy in order to block the unwanted surge of androgens.

Goserelin therapy has been shown to have an advantage in local control of prostate cancer, and an advantage in overall survival for patients with high-risk features, such as high PSA and/or high Gleason scores. The amount of time that the androgen deprivation therapy is to be given is controversial. In patients with large tumors, high PSA, and advanced Gleason scores, it is recommended that the patient stay on goserelin for 3 years (as per the study that demonstrated the survival benefit, Bolla et al.) up to a lifetime (as per the subgroup in the RTOG 85-31 study). For other lower-risk patients, it has been debated whether goserelin treatment is needed at all, or for shorter periods of time than the high-risk group above.

Some of the side effects of goserelin include impotence and hot flashes similar to what women go through with menopause. The hot flashes are typically intermittent and can improve or resolve with time on the medication. The impotence is usually a temporary symptom that persists as long as one remains on the medication. Once the goserelin is stopped, sexual function and testosterone levels should gradually return to what they were prior to goserelin. However, there are some data to suggest that those men who are on androgen ablation therapy for relatively longer periods of time (several years) are less likely to recover pre-treatment testosterone levels and/or will have a slower, more prolonged recovery back to baseline. Similarly, sexual drive or libido is diminished with goserelin, but typically this is also temporary. With external beam radiation therapy alone, the incidence of impotence is just over 50% at three years after treatment. There should not be any urinary or rectal incontinence caused by goserelin.



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