Case 2: A 50-year-old man presenting with metastatic prostate cancer at initial diagnosis

History

This man presented to his local physician with a chief complaint of intermittent back pain. He was managed for several months on a variety of nonsteroidal anti-inflammatory agents. Suddenly, he developed acute urinary retention and was seen by his local urologist, who detected a very large prostate that he thought was related to benign prostatic hyperplasia. The patient did well after his catheter was removed, and a transurethral resection of the prostate was discussed. A few more months passed, and during this entire time the patient’s PSA had not been checked.

Approximately eight to 10 months after the initial incidence he developed back pain again. The primary care physician finally ordered an X-ray, which didn’t reveal a compression fracture or any major pathology; however, the bone appeared a little opacified and was suggestive of metastatic disease. A bone scan revealed widespread metastatic disease. The PSA at diagnosis was 230 ng/mL and the prostate biopsy revealed Gleason 4 + 5 cancer.

Discussion

This man was in the poor-risk category; he had a high Gleason score, a high PSA and a large prostatic mass. He was referred to us for possible enrollment in early treatment trials. Unfortunately, he had already started hormonal therapy — bicalutamide and leuprolide — and that excluded him from the protocols. If he had not been treated with hormones and did not have metastatic disease, he would have been eligible for neoadjuvant treatment (docetaxel and estramustine; or paclitaxel, estramustine and carboplatin followed by radiation therapy).

Because he had been on hormonal therapy for two to three months with no improvement in quality of life and a very slowly declining PSA, he was treated with docetaxel and estramustine in addition to hormonal therapy. His family was devastated and he was convinced death was around the corner because his urologist had told him that he would probably be dead within a year. I find this very disconcerting, because for every Gleason grade the outcome can be variable. Some patients with Gleason 9 cancer live for 10 years before their disease progresses, and other patients with Gleason 8, 9 or 10 cancer can have a demise within two years. Even with metastatic disease, some patients with high-grade lesions seem to progress more rapidly than others.

If this patient had presented to me without having received hormonal therapy and was not eligible or didn’t want to participate in a study, I would have discussed the standard of care, the relative merits and deficits of hormonal therapy and the likelihood that his disease would not go into remission. I would have started him on an LHRH analog with or without an antiandrogen. Strong data do not exist to support the use of combined androgen blockade. We use it because we learned many years ago that the addition of an antiandrogen provides a sevenmonth survival benefit. Nevertheless, several meta-analyses and reviews have supported the use of monotherapy with an LHRH analog. As a rule, however, I use combined androgen blockade despite what the data show.

We are seeing more younger men who, at initial diagnosis, have metastatic disease. We don’t know why this is occurring. Are physicians reluctant to check PSAs in their younger patients because it’s not considered the standard of care or allowed by some insurance companies? We do not know.

Case 3: A 62-year-old man treated with bicalutamide monotherapy for prostate cancer recurrence

History

Several years after prostatectomy, this patient was started on bicalutamide 50 milligrams daily for biopsy-proven recurrent prostate cancer in a palpable inguinal lymph node. He was married to a woman who was about 25 years his junior, and sexual potency was an important issue. He had asked me about bicalutamide 150 milligrams, and we discussed the rationale for using leuprolide as the standard of care and the risks of not being on an LHRH analog. We also talked about investigational trials, but he did not wish to sacrifice potency at any cost. He wanted to try bicalutamide.

We tried intermittent bicalutamide 50 milligrams for about a year and a half, and he did very well. Then, several other lymph nodes evolved in the groin and retroperitoneum. I was ready to initiate leuprolide, but he did not want it. He was comfortable with bicalutamide, so we increased the dose to 150 milligrams. For two years, the lymph nodes regressed and he did wonderfully. While he was on bicalutamide 150 milligrams, he maintained his libido and had no complaints other than significant gynecomastia, which was tolerable. More recently, the lymph nodes grew to 50 percent of their previous size and his PSA started to rise. We have stopped the bicalutamide and we’re starting leuprolide.

Discussion

The only data evaluating monotherapy with bicalutamide 50 milligrams daily in patients with metastatic disease are from a study by Gerry Chodak. Because I have had several patients who didn’t want to receive leuprolide or an investigational treatment, I have used bicalutamide 50 milligrams daily on an intermittent basis. Usually these patients have only a rising PSA and not metastatic disease. If they do have metastatic disease, it’s a moderate amount of adenopathy in the retroperineum. I allow their PSAs to nadir to about 1 ng/mL because if I let them go beyond 1 ng/mL for a long period of time, the disease can become resistant. It takes about two or three months for the PSA to nadir at 1 ng/mL; then we stop the bicalutamide, allow the PSA to rise to whatever panic value that patient sets and then restart bicalutamide. Many of my patients have been following this strategy of intermittent bicalutamide for about three or four years.

Indications for chemotherapy

I have not utilized adjuvant chemotherapy in a nonprotocol setting and generally do not recommend chemotherapy in men with PSA relapse until they are resistant to hormones. Most clinical oncologists do not rush to administer chemotherapy in these settings. If the patient does not experience a durable response — less than six months — with hormonal therapy, then I’d immediately proceed to chemotherapy.

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Dr Slovin is an Assistant Member of Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center in New York, New York.