Case 1: A 52-year-old man with Gleason 7 prostate cancer

History

This young executive had a normal digital rectal exam and a PSA that was on the higher side of normal, but less than 4 ng/mL. His primary care doctor was concerned and sent him to a urologist for a biopsy. His prostate volume was only 18 cc, and all eight cores were positive for cancer with a Gleason score of 4 + 3, which automatically put him in a high-risk category. His urologist recommended a radical prostatectomy, and he was a good surgical candidate.

Discussion

I usually spend about 30 to 45 minutes with patients like this because I not only review the surgical technique, but also the patient’s “prostate profile” — his age, medical condition, pathology, total volume of disease, PSA and rectal examination. This patient’s actuarial survival was 86 years of age, which meant he had 34 more years to live — but he had high-volume and high-risk disease with every core positive.

This man had been divorced for two or three years and was now involved with a woman whom he was going to marry in six months. Because his sexual function and quality of life were of paramount importance to him, and he wanted to have his nerves spared, I told him, “You have high-risk bilateral disease. If a surgeon tries to ‘peel off’ the nerves, they’re going to leave cancer behind. You need a wide excision. I know you don’t want to hear it, but that’s what I’m going to recommend.”

Other options included external beam radiation therapy, radioactive seeds or a combination. However, patients with high-risk and high-volume disease do not do well. He also had a small prostate; hence, radiation could interfere with his bladder and rectum more than if he had a bigger prostate. Additionally, if he were to have a PSA recurrence two years from now, we would not be able to operate because the tissue would have been radiated.

He has decided to have a wide-excision prostatectomy. His chances of being cured are markedly improved if he receives 12 months of hormonal ablation. If he does not receive any treatment, he will have a 30 to 40 percent risk of PSA recurrence in the next two to three years. If he does receive treatment, his PSA will be zero. We do not have enough long-term data, so it is difficult to estimate his chances of being off of therapy and without evidence of disease in 10 years.

Prostatectomy for patients with high-risk disease

Currently, we treat patients with high-risk disease differently than we did one or two years ago. Now we do a wide-excision prostatectomy, removing the nerves and the surrounding tissue. Then we would check the PSA at six and 12 weeks. If the PSA is negative and the lymph nodes are negative, we recommend participation in SWOG-S9921 (2.1). In that trial, patients with high-risk disease are randomly assigned to receive hormonal ablation for two years with or without chemotherapy. In patients with high-risk disease who do not enroll in SWOGS9921, we use leuprolide or goserelin in combination with bicalutamide for a period of 12 to 24 months.

In patients with high-risk disease, postprostatectomy PSAs at six and 12 weeks that are not zero signify that the patient already has systemic disease and should receive total androgen ablation — bicalutamide and an LHRH analog — for a two-year period.

Managing patients with a PSA relapse

PSA relapse is not unusual — even patients with negative margins can have up to a 20 to 30 percent risk depending on the extent of capsular penetration. I have had patients whose PSA was negative for 10 or 11 years; then, all of a sudden, it crept up to 0.1, 0.2, 0.4 ng/mL, and two years later it was 1.0 ng/mL or more.

More common, however, are the patients with negative margins who have a PSA recurrence after one or two years. The management of these patients is more of a challenge; we don’t jump right away to treat them. If their PSA has gone from zero to 0.1 or 0.2 ng/mL, we tend to check another PSA to determine the PSA velocity. Three months later, if the PSA has gone from 0.2 to 0.8 ng/mL, we have a problem. If, instead, the PSA has gone from 0.2 to 0.3 ng/mL, it’s less worrisome.

The data indicate that these patients need to be treated by the time their PSA is 1.0 ng/mL. Previously, we would wait until the patient was symptomatic to start treatment. Now, early androgen ablation is recommended, but it all depends on the patient. I tell them, “I don’t want your PSA to go above one. So, sometime between now and then, I would like to give you external beam radiation therapy.” Usually, we send them for external beam radiation therapy to the prostatic bed. If the rise in PSA is rapid, radiation therapy may not be sufficient, in which case we use androgen ablation with or without radiation therapy. When the radiation is complete, we discontinue the hormonal ablation and evaluate the PSA.

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Dr Thomas is a Professor and the Chairman of the Department of Urology at Tulane University’s Health Sciences Center in New Orleans, Louisiana.