History Holds Men's Cancer Clues


Prostate cancer sufferers who have a family history of the disease are more likely to have a relapse and more likely to die from the disease than are men without a family history, according to Dr. Patrick Kupelian of the Cleveland Clinic Foundation in Ohio.

Men with such a history--either a father or a brother with prostate cancer--should undergo screening at an earlier age and, when a tumor is detected, should be treated more aggressively, he told an American Cancer Society briefing for reporters in Newport Beach last week.

Prostate cancer will strike an estimated 184,500 American men this year, with an expected 39,200 deaths, making it second only to lung cancer as a cause of cancer deaths among men.

Kupelian studied 720 men who had undergone a prostatectomy between 1987 and 1996. Five years after their operations, 64% of those with a family history of prostate cancer had suffered a relapse, compared with only 46% of those without a family history. Similar results were also observed among patients who underwent radiation therapy.

Men who have a family history of the disease should probably undergo screenings starting at 40, rather than the now-recommended 50, Kupelian said. Such men may also be good candidates for chemoprevention with drugs such as Proscar. And if and when a tumor is detected, he added, surgeons should make a more aggressive search for metastasis.

Researchers look for such metastases in the pelvic lymph nodes, which are closest to the prostate. Even in patients at high risk for recurrence, however, the search often reveals no trace of prostate cells. But that situation may change because of a new test developed by Dr. Anna Ferrari of the Mt. Sinai School of Medicine in New York City.

Ferrari told the ACS meeting that prostate cells contain two unique proteins, PSA and PSMA. She has developed a test for the genetic material used to produce these proteins and is now able to show the presence of one prostate cell among 10 million lymph node cells.

She examined pelvic lymph nodes from 72 prostate cancer patients with a high risk of recurrence. Conventional pathology tests showed metastasis in 8% of the patients, but her test found biochemical evidence of metastasis in 85%. Previous studies had shown that 50% to 90% of high-risk patients suffered a relapse after initial treatment, in line with her findings.

She speculated that immediate systemic treatment of these patients could potentially be lifesaving by killing the metastatic cells before they have a chance to establish new tumors.

Meanwhile, Dr. Gerald Murphy of the Pacific Northwest Cancer Foundation in Seattle reported preliminary results with a new technique for treating terminal prostate cancer patients. He and his colleagues extracted a type of immune cell called dendritic cells from the patients, grew large quantities in the laboratory and then reinfused them into the patients, either alone or in combination with fragments from the PSMA protein.

Their goal was to stimulate the patient's immune system to attack tumor cells in his body.

In the first group of 33 patients Murphy studied, nine showed a reduction of their metastases, as indicated by biochemical markers; 11 showed no further progression of the disease; and 13 continued to show progression.

Twelve of the patients have now survived for more than 600 days, Murphy said. The median survival time for terminal patients like these, in contrast, is only 180 days. Murphy plans to expand the trials to other medical centers in the near future.

A new way to treat solid tumors throughout the body was described at the meeting by Dr. Harinder Garewal of the VA Medical Center in Tucson. Solid tumors are difficult to treat by chemotherapy because the high doses of drugs necessary to kill the tumor cells produce toxic effects elsewhere in the body.

Garewal has been working with an unusual gel produced from cow collagen. The gel is liquid at room temperature, but becomes thicker, "like honey," at body temperature, he said.

Garewal dissolved the toxic cancer drug Cisplatin in the gel, along with epinephrine, which restricts blood flow by constricting blood vessels. This liquid is then injected into tumors, where its viscosity increases. The drugs are thus confined to the tumor rather than spreading throughout the body.

In preliminary studies on patients with advanced head and neck tumors, Garewal observed a complete response--death of the tumor--in 30% of patients and a partial response in 20% of the others. None of the patients suffered any side effects from the treatment. Conventional treatment of such tumors is successful in only 10% to 15% of such tumors, he noted.

Garewal is now conducting a placebo-controlled trial of the therapy in which 90 patients will be enrolled.

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