Treatment Options For Recurrent Cancer

There are two goals in treating prostate cancer that has spread: (1) improve the quantity of the man's life, and (2) improve the quality of the man's life. The dilemmas in treatment arise when attempts to improve quantity make the quality worse, not better. Honest assessments of treatment options are crucial to resolving these dilemmas.

The mainstay for treating recurrent prostate cancer is hormone therapy, as described in Chapter 5. Prostate cancers use testosterone to grow, so blocking testosterone slows the growth. Prostate cancers contain cells that are sensitive to testosterone and other cells that are not sensitive. Over time the testosterone-insensitive cells become predominant and hormone therapy becomes ineffective. The cancer is then called androgen independent. The average duration of effectiveness for hormone therapy for a prostate cancer that has already metastasized is approximately two years,10 but during that time men often have comfortable remissions.

One of the two major controversies in providing hormone therapy to men with recurrent prostate cancer concerns when to start the treatment: as soon as the PSA rises, or not until the cancer metasta-sizes or otherwise causes symptoms of growth. Proponents of immediate treatment point to two studies reporting that immediate hormone therapy produced better outcomes. In one study, men treated with immediate hormone therapy, compared to those for whom hormone therapy was delayed, developed metastases more slowly, had half the number of serious complications (pathological fractures, spinal cord compression, obstructions of the ureter), and survived longer. In the other study, at seven years after treatment only 6 percent (3 of 47) of the men who had received immediate hormone therapy had died from prostate cancer compared to 31 percent (16 of 51) of the men who had received delayed therapy.11

Proponents of delayed hormone therapy point to an older study that had results exactly opposite to the two studies cited above. They also argue that giving hormones to men before there is evidence of cancer spread means subjecting them unnecessarily to the multiple side effects of hormones. Patrick Walsh, a staunch opponent of immediate hormone therapy, says that it ''will actually take life out of the years a man has to live, without adding any years to that life.'' Walsh also notes that the pharmaceutical industry has strongly influenced urologists to start hormone therapy early because the industry ''makes at least a billion dollars a year on hormonal agents for the treatment of prostate cancer.''12 Several studies are under way that perhaps will resolve the immediate versus delayed treatment debate.

The other active hormone therapy controversy is whether to give hormones continuously or intermittently (in other words, treat the man for a few months until his PSA falls and then stop treatment for several months until the PSA rises again). The two arguments for intermittent therapy are that it gives the man a better quality of life by giving him a ''vacation'' from the hormone therapy side effects, and that intermittent therapy delays the process of the cancer's becoming androgen independent.

Some but not all studies support these arguments. A European study reported that only 7 percent of men on intermittent hormone therapy had had progression of their cancer at the end of three years compared to 39 percent of the men on continuous hormone therapy. A U.S. study found no difference in progression rates between the two groups. There does appear to be consensus that the quality of life is better for men on intermittent therapy, since they have periods free from the side effects of the therapy;13 therefore, intermittent therapy is being increasingly used. Two large studies comparing continuous and intermittent hormone therapy are in progress.

Beam radiation is the second most commonly used treatment for men who have recurrent prostate cancer. It can be utilized in one of three ways. First, as what is commonly referred to as adjuvant therapy, beam radiation can be used immediately following surgery to radiate the prostate bed in men at high risk for cancer recurrence— say, with a Gleason score of 8 to 10. At least ten studies have suggested that this therapy may reduce, or at least delay, the chances of recurrence of cancer.14 Radiating the prostate bed after surgery, however, carries with it an inevitable increase in incontinence,

Intermittent Hormone Therapy

I was first diagnosed with prostate cancer at the tender age of 36. Subsequently, . . . I went through the conventional treatments of radical prostatectomy and . . . radiation therapy to the prostate bed. . . . Five years later in 1989 I was faced with a new problem: It became apparent that my PSA . . . was rising significantly. . . . The conventional wisdom at the time was for me to undergo immediate castration—a more than terrifying prospect especially for a psychiatrist like myself with some background in studying Freud. . . . [A urologist suggested intermittent hormone therapy.] Instead of my facing a permanent blockade of testosterone, this protocol lasts for only nine months at a time, followed by two years of normal testosterone levels. His recommendation has proved to be objectively correct. Friends and colleagues who underwent permanent castration when facing a similar bind at the same time have all since died.

—Paul Steinberg, ''Safety in Numbers,'' Washington Post, August 24, 2004

impotence, rectal bleeding, and other side effects. And since it is not known which cancers are going to recur, many men are unnecessarily irradiated.

The second use of beam radiation for cancer recurrence is called salvage radiation therapy. It is utilized once the PSA rises, indicating that recurrence has taken place. The radiation is directed at the prostate bed, where it is assumed some prostate tissue is growing. This approach has become increasingly popular as the first choice for treatment when cancer recurs after surgery, with many men saving hormone therapy for later use if needed. Although no studies have yet demonstrated that salvage beam radiation prevents the development of metastases or lengthens life, several studies have reported promising results: one large study found that 45 percent of the men

Is God Besotted with Irony?

I do get profoundly sad thinking of what has been and is no longer: people, places, things. And in my art I've tried again and again to find ways to hold on to the precious in the present, to memorialize what is essential to me as an observer of my time, to make history come alive so that souls long dead will still have meaning. Indeed, is it not wonderfully ironic that I worked for twenty-six years writing a book which investigates a suicide, while during the past eight and a half years I've been fighting to stay alive because my prostate cells refuse to commit suicide (which is what healthy cells do)? Is God besotted with irony?

—Gordon Sheppard, a Canadian writer with metastatic prostate cancer, ''The Wondrous World of Prostate Cancer,'' unpublished essay had no progression of their cancer during the four-year follow-up period. Not surprisingly, the men most likely to respond to salvage beam radiation are those who have a low Gleason score, who have a prolonged PSA doubling time, and who began treatment immediately after their PSA rose.15

The third type of beam radiation for prostate cancer recurrence is palliative therapy. It is used for cancers that have spread locally or metastasized to bones or other organs. The intent is to shrink the tumor and thereby provide relief of pain. Such radiation is commonly used in the late stages of the cancer.

Hormone therapy and beam radiation are the most commonly used treatments for recurrent prostate cancer. Surgery is little used except in a few centers, because removal of the prostate after beam or seed radiation therapy is technically very difficult and carries a high incidence of incontinence and other side effects. Seed radiation therapy has been tried following beam radiation or cryotherapy failure, but the results have not been promising. Cryotherapy is sometimes utilized for recurrent cancer following seed radiation, but its use following beam radiation or surgery has not been encouraging. In assessing all these secondary treatments, we need to carefully weigh possible benefits against the virtually certain serious side effects.

Chemotherapy is often tried in the late stages of recurrent prostate cancer but with limited benefit. It is relatively ineffective for prostate cancer, in contrast to many other human cancers. Chemotherapy works best on cancer cells that are dividing very rapidly, and prostate cancer cells divide slowly compared to other cancers.

The most promising chemotherapeutic regimen for prostate cancer to date has been docetaxel (Taxotere), a drug that has been used to treat breast cancer, in combination with estramustine (Emcyt) or prednisone. In late 2004 these combinations were shown in clinical trials to lengthen the life of men with advanced prostate cancer by approximately two months.16 This was the first time that any chemotherapeutic agents had been demonstrated to have an effect on prostate cancer survival. Many other drugs are being tested, including etoposide (VePesid), mitoxantrone (Novantrone), paclitaxol (Taxol), carboplatin (Paraplatin), and vinblastine (Velban). Generally these drugs are used in combination with each other or with hormone therapy.

Chemotherapeutic agents do have significant side effects: hair loss; fatigue; nausea and vomiting; bone marrow suppression, causing anemia and increased susceptibility to infection; and allergic reactions. Estramustine, one of the most widely used drugs, can also cause blood clots, which can be fatal. Most of these drugs must be given intravenously every three to six weeks.

Some men with advanced prostate cancer decide to enroll in clinical trials of experimental drugs other than chemotherapeutic agents. Such trials are usually carried out at university medical centers in three phases: phase I assesses whether the drug is safe to be given to humans, phase II assesses its efficacy dose in a few men, and phase III tests its efficacy in a large number of men.

Among the most promising ongoing clinical trials are those testing vaccines that tell the body's immune system to attack the cancer. In 2005 the results of a trial of one vaccine, Provenge, appeared to be moderately hopeful. Other drugs being studied are those that inhibit growth factors, cut off the cancer's blood supply (angiogenesis inhib itors), promote the death of cancer cells (apoptosis), and inhibit specific enzymes needed by the cancer cells (for example, cyclo-oxygenase inhibitors such as COX-2).17 The best way for men to stay current on these studies is by perusing the websites recommended in Appendix C, especially those marked with asterisks.

It has proven to be relatively difficult to persuade men with advanced prostate cancer to enroll in clinical trials. It was estimated in 2003 that four times more women (34,757) were enrolled in breast cancer trials than men (8,309) in prostate cancer trials.18 A major reason is that most men with advanced prostate cancer are older than most women with advanced breast cancer, and they are not as willing to try to extend their lives for a few additional months. Such trials, however, are essential to finding new and better treatments. Men who wish to identify ongoing clinical trials for which they may be eligible can do so by going to the website of the National Cancer Institute (www.cancer.gov) and clicking on ''Clinical Trials.'' They can also access this information directly by going to a website developed by the National Library of Medicine, www.clinicaltrials.gov (type in ''Prostate Cancer'' and your city). Another source of information on clinical trials is a commercial website, www.centerwatch .com, which includes a list of drug trials being sponsored by pharmaceutical companies (click on ''Oncology,'' then on ''Prostate Cancer'').

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