Testicular Cancer Update: Building on Success
It's hard to find a more potent symbol of victory over cancer than world champion cyclist Lance Armstrong as he gears up for his final Tour de France race next month. Through his recovery from testicular cancer in 1996 - and his incredible athletic achievement on the Tour - Armstrong has given hope and determination to countless cancer patients, clinicians, and researchers.
Equally incredible are the tremendous strides in treatment of testicular cancer, the most common cancer to strike young men between 15 and 35 years of age, which was uniformly fatal. In recent years the rate of cure for early-stage disease approaches 95 percent. Key to that dramatic turnaround was the introduction during the 1970s of cisplatin (Platinol) into standard treatment regimens, through the pioneering work of Dr. Lawrence Einhorn and his colleagues at the Indiana University Cancer Center. Armstrong received his successful cancer treatment from Dr. Einhorn.
"The chemotherapy treatment for this disease is so successful, it's almost a miracle," notes Dr. Marston Linehan, chief of NCI's Urologic Oncology Branch.
Dr. Einhorn and others have also developed and refined highly effective surgical techniques, which, in many cases, are able to cure the disease without chemo or radiation. These include orchiectomy (surgery to remove one or both testicles) and removal of lymph nodes in the abdomen, called retroperitoneal lymph node dissection or RPLND. (The lymph nodes act as the primary route for metastases in testicular cancer.)
Despite these huge successes, researchers and clinicians are seeking further improvements in treating testicular cancer, including finding ways to minimize long-term side effects of the treatments themselves.
At last year's annual meeting of the American Society of Clinical Oncology, Dr. Timothy Oliver of St. Bartholomew's Hospital in London presented findings from 1,400 patients showing that after 4 years of follow-up, one course of carboplatin medication appeared as effective as radiation therapy in treating early seminoma - a common form of testicular cancer. Most important, the drug also appeared to reduce the risk of second cancers, compared with radiation.
"There are also some interesting questions being developed about the potential role of minimally invasive surgical approaches to treatment of testicular cancer," Dr. Linehan says.
For example, attention is being focused on whether laparoscopic surgery for RPLND is as effective as the current "open" surgery approach. Dr. Joel Sheinfeld, vice chairman of Urology at Memorial Sloan-Kettering Cancer Center, observes that this new approach remains subject to debate: "It's unclear what is the therapeutic efficacy of laparoscopic surgery as compared with open RPLND, where the therapeutic efficacy is well established," he says.
Memorial Sloan-Kettering plans to initiate a study of the less invasive RPLND technique, Dr. Sheinfeld continues. "We're going to do a study of the laparoscopic operation so that it exactly mimics the open operation. This will be for patients with low-stage, seminoma stem cell tumors. Patients with low-volume disease will not get chemotherapy."
Dr. Sheinfeld and colleagues also recently published a study in the Journal of Clinical Oncology assessing the impact of Memorial Sloan-Kettering's stringent selection guidelines for RPLND candidates. "We've learned over the years to exclude from surgery certain patients with elevated markers after orchiectomy because the likelihood of failure is so high." Since 1999, the institution has limited the procedure to only patients with low-volume disease in the retroperitoneum who are less likely to relapse. "If you look at the old data, the relapse rates were 20 to 30 percent; now it's fewer than 10 percent," Dr. Sheinfeld adds.
NCI scientists are also studying hereditary forms of testicular cancer. This is a follow-up to the discovery of a familial testicular cancer susceptibility gene on the X-chromosome (the chromosome that men inherit from their mothers), named the Testicular Germ Cell Tumor-1 (TGCT1) gene.
Dr. Mark H. Greene, chief of the Clinical Genetics Branch, is leading the Institute's Familial Testicular Cancer study, which seeks to "find the gene or genes that cause this type of cancer to occur in families." The study seeks to enroll 750 individuals from families with a history of testicular cancer. Some of the participants will be invited to the NIH Clinical Center for more detailed clinical/genetic/laboratory studies designed to identify other factors that may contribute to the development of familial testicular cancer.
NCI is also conducting a case-control study of testicular cancer among members of the U.S. Armed Forces. Dr. Katherine McGlynn, principal investigator in the Hormonal and Reproductive Epidemiology Branch of DCEG, is investigating environmental and genetic determinants of risk among approximately 800 testicular cancer cases and 800 controls, along with information from approximately 1,000 mothers of study participants.
"It is hoped that by increasing knowledge about the causes of testicular cancer, prevention and surveillance strategies will be developed which will be beneficial to future families with an increased risk of developing this cancer," Dr. Greene comments. For more information on NCI's clinical genetics testicular cancer study, go to http://familial-testicular-cancer.cancer.gov/index.html.
By Bill Robinson