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Prostate cancer: physicians weight in on Treatment options.

Prostate cancer is the most common form of cancer in men. Prostate cancer is also noteworthy because it remains among the most treatable forms of cancer. If caught early enough and treated properly, the disease has one of the highest rates of remission. What are the available treatments, and how do patient and doctor alike go about making a decision that could save a life?

In December of 2008, the NEJM presented a prostate cancer case along with three treatment options, and then polled physicians to see which treatment was the most popular choice. The doctors were asked to base their opinions on the published literature, their own knowledge and past experience of the condition, recent guidelines, and the points outlined by the clinical experts with each given treatment option. The voting results, preceded here by a summary of the case and of each treatment, are illuminating and can hopefully help everyone understand some of the medical thinking pertinent to this vital issue.

The patient in this case is a 63-year-old man with a rising prostate-specific antigen (PSA) level. The author makes clear that there may be more than one appropriate treatment. The patient had no symptoms and was physically and sexually active. Biopsy of the prostate revealed adenocarcinoma; the tumor has a length of about 5 mm. The patient plans to continue to run his advertising business. He does not smoke, drinks only occasionally, and jogs 2 miles three times a week. He has inquired specifically about expectant management.

The treatment options are as follows:

Treatment 1 - Expectant Management

Expectant management, also known as active surveillance, was brought up for discussion by the patient himself. A key question in this case is whether the cancer is potentially indolent, in which case treatment can be deferred or possibly avoided completely.

According to a nomogram, the patient's risk of having potentially indolent prostate cancer is 72%. With a probability threshold of 70% for identifying an indolent cancer, a doctor can legitimately consider expectant management for this patient.

If the patient chooses this option, a strict follow-up regimen is required, including the measurement of PSA level and digital rectal examination every three months for two years. The clinical expert who presented this treatment option notes that biopsy should be repeated after three months or one year, or both.

In the doctor's words, "There is, however, a serious limitation to this option. A PSA doubling time of 1.8 years translates into a PSA velocity of 0.77 ng per milliliter per year. If this rate of increase in the PSA level is confirmed in our patient, I would have to recommend active treatment."

The clinical expert goes on to say that a PSA doubling time of more than 15 months is associated with death from any cause within a median of 15 years, whereas the median time to death from prostate cancer was not yet reached at 16 years.

"With proper information on risks and potential benefits, the patient could be supported in his choice of active surveillance. The benefit would be the avoidance of the adverse effects of treatment. But if PSA levels increase at the same rate within two or three more observation periods of 3 months each, my advice would change."

Treatment 2 - Radiotherapy

A permanent prostate seed implant involves the placement of radioactive seeds directly into the prostate under guidance of transrectal ultrasonography. The major goals of this treatment are to control cancer, preserve sexual function, and maintain urinary continence while minimizing the risk of serious rectal or bladder complications. Permanent prostate seed implantation appears to have a more pronounced effect on prostate tissues than external-beam radiotherapy. This second prostate cancer expert notes that, "When assessed by means of endorectal magnetic resonance imaging and spectroscopy, the median time to the resolution of spectroscopic abnormalities was 32.2 months with external-beam radiotherapy and 24.8 months with permanent prostate seed implantation. Moreover, the degree of atrophy and the magnitude of the decline in PSA levels were more pronounced after a permanent seed implantation than after external-beam radiotherapy."

In considering this option, it's worth pointing out that the experts agree that the key to a successful outcome after permanent prostate seed implantation is to deliver a high dose of radiation to the entire prostate while sparing adjacent normal tissues. These goals are generally best accomplished by ensuring that the procedure is performed by an expert team including a radiation oncologist, a urologist, and a medical physicist.

Treatment 3 - Radical Prostatectomy

Physician 3 writes, "This patient has a multifocal prostate cancer (present in 2 of 12 needle-biopsy cores) of intermediate grade (Gleason score of 6). His PSA level, although relatively low (3.8 ng per milliliter), has risen rapidly (1.15 ng per milliliter per year on average) over the past 2 years. He has a small prostate for his age (volume, 22[cm.sup.3]), and his PSA density is high. The PSA velocity and density suggest a larger volume and more aggressive cancer than is indicated by the biopsy, which often underestimates the extent of cancer."

The author illuminates that in population-based studies, as compared with expectant management, active treatment with surgery or radiotherapy within six months after diagnosis reduced the risks of death from any cause and from prostate cancer. "Radiotherapy is associated with 5-year rates of cancer control similar to those with radical prostatectomy and could be used to treat this patient's cancer. However, effective radiation requires very high doses and is associated with troublesome sexual and urinary side effects or bowel side effects. With radiation, it is difficult to be sure that the cancer is eradicated, since PSA levels rarely become undetectable. Local recurrence tends to be detected late, if at all, when additional local therapy is hazardous and seldom effective.

Given this patient's low PSA level and small-volume cancer on biopsy, it is highly likely (probability, 88%) that his cancer is confined to the prostate gland, making him an excellent candidate for nerve-sparing surgery. The operative mortality rate in a healthy 63-year-old is less than 0.1%."

In a multi-institutional longitudinal study of the quality of life after radical prostatectomy, two years after the procedure, 20% of patients reported incontinence requiring the use of one or more incontinence pads daily, but urinary obstruction and irritation improved significantly. Sexual function deteriorated in the first three months but had improved at years. The best result was in young men with low PSA levels who had undergone "nerve-sparing surgery."

Voting Results

Among the 3,720 votes cast, 29% were for expectant management, 33% for radiotherapy, and 39% for radical prostatectomy. Most voters were physicians (over 2,600), but some were students or patients who had received treatment for prostate cancer.

The journal writes that the almost even distribution of votes among the three options is somewhat surprising. Many voters who favored expectant management actually wanted to wait several months to determine whether the PSA continued to rise. They were actually voting for a delay before invasive treatment, not for years of such management. Ultimately, most voters in favor of expectant management would have to choose a treatment.

Readers who voted in favor of radiotherapy and commented on their vote were inclined to emphasize that the risks of incontinence and impotence were lower after the placement of radioactive seeds than after radical prostatectomy. Comments in favor of prostatectomy stressed the long life expectancy of the patient, his lack of coexisting conditions, and the relatively small size of his prostate. Many commenters emphasized the importance of the surgeon's level of experience in performing a nerve-sparing prostatectomy.

The even distribution of opinions we received from over 2600 physicians about the management of prostate cancer is a compelling argument in favor of a definitive clinical trial to settle the issue of radiotherapy versus surgery.

NEJM, 2009, Vol. 360, No. 3, e4,

NEJM, 2008, Vol. 359, No.24, pp. 2605-2609, jpsecsha
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Publication:Running & FitNews
Article Type:Case study
Geographic Code:1USA
Date:Jan 1, 2009
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