NewlingresponsetoLiebowitz

"Focused on the Prostate since 1996"

D. Newling responds to Dr. Liebowitz' assertions:

(http://rattler.cameron.edu/prostate/leibowitz/, Emerging concepts in prostate cancer 1997-2000). Dr Leibowitz does not believe in surgery or radiation therapy as primary treatment for localised prostate cancer. Instead, he advocates widespread use of 12-14 months of triple hormonal therapy, using an LH-RH agonist, flutamide and finasteride. Dr Leibowitz maintains that radical prostatectomy is not indicated in the majority of patients and there is no evidence that radiation therapy achieves significant cure rates. His figures for his so called complete remissions, while dramatic, only involve relatively small numbers of patients. He maintains that triple hormone therapy does cure prostate cancer and quotes some articles on the histological examination of prostates removed after 6-8 months of maximal androgen blockade in neoadjuvant protocols. He quotes a figure for 40% of cancer negative specimens, which is 4 times as high as the most commonly accepted figure. It is true that, by routine histological examination after hormonal therapy, cancer cells are difficult to find, but using markers of epithelial proliferation, they can be shown in the vast majority of specimens still to be present.

As far as the side effects of radical prostatectomy are concerned, an impotence figure of 85% includes those 50% of patients who were impotent before the operation. The actual overall rate of impotence after radical prostatectomy carried out with nerve sparing intent, is less than 30%. It is also maintained on this website, that 30% of patients require further therapy after radical prostatectomy. This figure would seem to be dramatically higher than the large series from the Mayo Clinic and the John Hopkins, where for T2 cancers, the 15-year survival rate is around 85%. The figures quoted by Dr Leibowitz are true for patients presenting with T3 tumours, the majority of whom are not offered radical prostatectomy as primary therapy in this day and age. Also quoted, is the suggestion that radiation therapy adds nothing to hormonal therapy in locally advanced disease. The recent studies of the Radiation Therapy Oncology Group (RTOG) mentioned previously, refute this and show that 2 months of maximal androgen blockade, followed by radiation therapy and 2 further months of hormonal therapy, improve progression-free survival by over 30% compared with radiation alone. However, it must be accepted that the RTOG study has not compared hormonal therapy alone against combination therapy. Of more interest is the study reported by Bolla et al (Bolla M et al. N Engl J Med 1997; 337: 295-300), where 415 patients were given routine radiotherapy for locally advanced prostate cancer, half of whom subsequently received goserelin acetate for 3 years. Two years after the end of all treatment, progression-free survival in the combination arm was 85% compared with 48% in the other patients. There would thus appear to be at least two fairly large studies which contradict the view that the combination of hormone therapy and radiation is not effective.

It is true to say that the present role of hormone therapy in localised disease requires further investigation. Since it has proved impossible in two major attempts to carry out a 3-arm study of radical prostatectomy vs irradiation therapy vs watchful waiting, and therefore delayed hormonal therapy, it is only possible to look at studies of hormone therapy, ie, combination, or monotherapy in patients in whom it is acceptable not to offer any treatment. This will include many of the patients being given triple hormonal therapy by Dr Leibowitz at the present time.

Information to date suggests that in patients with M0 disease, monotherapy with a non-steroidal antiandrogen is as effective as surgical castration (an operation described by Dr Leibowitz as barbaric, forgetting perhaps that, in some parts of the world because of the high cost of hormonal therapy, there is no alternative). Once the number of receptors has risen, such as occurs in M+ disease, then castration (medical or surgical) is more effective. Treatment with a steroidal antiandrogen as monotherapy, probably falls into the same category, although, because of its inhibitory effect on the pituitary, it may be more suitable for slightly more advanced patients. The limitation of steroidal antiandrogens used in high doses as monotherapy, is that they can have side effects. There is no evidence that using multiple hormonal manipulations in early-stage localised disease, is better than a montherapeutic option, and even in locally advanced and metastatic disease, there are only a few studies which show that maximal androgen blockade is actually better than medical or surgical castration.

It would seem logical to initially treat patients who have no symptoms from their prostatic disease, with a therapy such as a non-steroidal antiandrogen, which will not give them severe symptoms. This may be used intermittently or continuously; as yet, there is no information that either regimen is of greater benefit. Additional hormonal therapies can be added for progression, either after a period off therapy, or if progression occurs on therapy. Multiple hormonal manipulations which guarantee impotence, loss of libido, ultimately loss of muscle mass and osteoporosis, should be reserved for those patients who are likely to, or have already, got symptoms.

January '98, UroWeb