Men’s Health

By Louise Lazear

Early diagnosis and treatment advances are keys to testicular cancer survivability

dm01.gif (7824 bytes)Testicular cancer (TC), although rare, is the most common cancer in males between the ages of 15 and 34. In 2001, 7,200 new testis cancer cases were estimated to occur in the United States, with an annual worldwide incidence of approximately five per 100,000. If diagnosed early, the disease is highly curable, with some patients approaching five-year survivability rates close to 100 percent. While researchers explore possible links between rising incidence rates in industrialized nations and environmental and genetic causes, early diagnosis and refined treatment protocols continue to increase survivability and improve the quality of life for men fighting this disease.

bHCG and AFP mark and monitor
Diagnosis of TC usually begins with the patient discovering a painless lump upon self-examination, or unusual swelling of one or both testicles. Initial work-up includes physical examination, ultrasound evaluation, and blood work to rule-out infection. Elevated levels of alpha-fetaprotein (AFP), beta-human chorionic gonadotrophin (bHCG), and lactate dehydrogenase indicate the presence and type of testicular cancer, as well as treatment efficacy. “The two tumor markers that are used the most are bHCG and AFP,” said Richard Foster, M.D., professor in the Department of Urology at Indiana University School of Medicine in Indianapolis. “They are useful in diagnosis because if a patient presents with a solid intertesticular mass and has elevation in these markers, then the diagnosis is virtually assured. But the most important characteristic of these markers is that they allow us to monitor the course of therapy without relying upon x-ray imaging studies.” Other markers, including immunohistological parameters that correlate with cell division, are under investigation. “But markers of proliferation are not as clinically useful as AFP and bHCG…in terms of managing these patients on a day-to-day basis,” Foster added.

Standard diagnostic work-up for TC also includes abdominal ultrasound, chest x-ray, and if metastases are suspected, CT of the chest, abdomen, pelvis, and brain. However, definitive diagnosis requires histological evaluation of the testicle, which is removed via an incision in the groin. This procedure, called radical inguinal orchiectomy, is preferred over localized biopsy to prevent extra-capsular dissemination of tumor cells, and to remove as much of the primary malignancy as possible. With one remaining healthy testicle, most patients retain normal sexual and hormonal function. However, some physicians establish baselines for testosterone and LH levels prior to orchiectomy for possible post-treatment supplementation, and offer patients the option of sperm preservation to alleviate concerns over future fertility.

Treatment by stage and cell type
Because the disease is so rare, most patients opt to undergo further evaluation and treatment at medical centers with expertise in treating TC, returning home after therapy under strict surveillance protocols that include monitoring of serum markers and imaging studies performed at specific intervals. Before treatment course is determined, however, the disease is classified into stages that define dissemination of tumor cells: Stage I describes cancer that has been confined to the testicle; Stage II indicates cancer that has spread to the retroperitoneal lymph nodes; and Stage III describes metastases to other remote sites, including the lung, liver and brain.

Treatment protocols also depend on cancer cell type. Approximately 95 percent of malignant testicular tumors arise from germ cells, the precursors of sperm. These malignancies are broadly classified into one of two types: seminomas, the most common cell type for TC; and nonseminomas, which include choriocarcinoma, embryonal carcinoma, teratoma, and yolk sac tumors. Most nonseminomas are a mixture of cell types, and the relative proportions of each type are determined upon pathological evaluation.

Dependent upon stage and cancer cell type, patients undergo further surgery, chemotherapy, and/or radiation therapy. Patients diagnosed with Stage I seminoma are typically treated with radiation therapy of the retroperitoneal lymph nodes, experiencing cure rates greater than 95 percent. Stage II seminomas are divided into bulky and nonbulky categories, and standard treatment is either radiation therapy and/or combination chemotherapy. Nonbulky stage II disease has cure rates over 90 percent with radiation therapy alone. Stage III seminoma has lower cure rates, and is typically treated with multi-drug chemotherapy

Treatment for Stage I nonseminoma disease includes retroperitoneal lymph node dissection (RPLD). Because the lumbar sympathetic nerve chain is intertwined with node drainage sites, specialized nerve-sparing procedures have been developed to preserve ejaculatory function. Some patients opt for surveillance alone if the cancer has remained localized. Stage II nonseminomous disease also has high cure rates (greater than 95 percent), and is treated with RPLD and chemotherapy. Stage III nonseminoma, which has cure rates of about 70 percent, is treated with standard chemotherapy.

Treatment of TC has not always been so successful, especially for patients with widely metastatic disease.

The model for cancer treatment of all types
The tide turned in the early 1970s when Dr. Lawrence Einhorn, an oncologist, found that TC had a profound sensitivity to platinum-based chemotherapeutic agents. Incorporating these agents into his treatment regimen, Einhorn’s patients experienced astoundingly high cure rates, which the oncology community hoped to replicate with other types of cancer. Unfortunately, such was not the case. But for TC patients, platinum-based chemotherapy in the form of cisplatin is now one of several factors contributing to a successful course of treatment. “Chemosensitivity is half the story,” said Michael S. Cookson, M.D., assistant professor in the Department of Urology at Vanderbilt University Medical Center in Nashville. “Although we benefit from the fact that germ cell cancer is exquisitely chemosensitive, it is a perfect union of a combination of therapies that makes testicular cancer so curable. It is the model for future advancement for treatment of cancer of all types.” Cookson added that early detection, due to increased awareness and self-examination, is another important factor contributing to the cure rates seen today. Due to the fact that currently there are no recommended biochemical screening tests for germ cell tumors, and because TC is so rare yet curable in most cases, some feel that increased awareness among young men would be more effective than development and promotion of screening methodologies like those used to fight other diseases, including breast and lung cancer.

Research and clinical trials
As treatment options for TC continue to evolve, surveillance alone is being investigated as an option for some men with low volume disease. Cookson and his colleagues at Vanderbilt are involved in a multi-site clinical trial to correlate results from diagnostic studies with the ability to assess for risk of recurrent disease in patients with Stage I TC. Other research is underway to improve the survivability of patients with poor risk disease, those with cancer cells that, for some unknown reason, do not respond as well to chemotherapy. “One of the most important clinical trials today is an international study randomizing treatment of poor-risk patients between standard chemotherapy, which is four courses of chemotherapy, and high dosage chemotherapy with stem cell support,” said Foster. “The purpose of the project is to determine whether higher doses of chemo are more curative in these patients. But the real advances will be contingent upon determining what makes poor risk disease “poor risk.”

Unlocking the genetic and molecular mechanisms that control TC’s chemosensitivity is a major area of research. In February 2000, UK researchers announced the discovery of a gene location on the X chromosome that could indicate a predisposition for the disease. Other teams are focusing on differences between TC cells that could impact sensitivity to treatment. For example, most patients who initially undergo treatment have cancer cells that are highly sensitive to chemotherapy. Later, in an unfortunate recurrence, some of these same patients develop cells that do not respond well to chemotherapy. “What happens to the cancer cells in that period of time between the initial diagnosis and late recurrence, no one really knows, ” commented Foster. Some feel that understanding this change in chemosensitivity could lead to developments in treating other cancers as well.

While risk factors for TC have been identified, including age, a history of undescended testicles, gonadal dysgenesis, familial history and a prevalence among white males, causes for TC remain under investigation. Links between TC, low sperm count and environmental toxicity have been widely publicized. Researchers in Ontario published results of a recent study that suggest young men with physically demanding jobs and teenage boys who exercise regularly may have a higher incidence of TC than their less-active counterparts. A quick glance at a list of “celebrity” victims, including two-time Tour de France winner Lance Armstrong, figure skater Scott Hamilton, and football player Brain Piccolo whose battle with the disease was portrayed in the emotional film “Brian’s Song”, would also tend to offer anecdotal evidence linking athleticism with TC. In this case, it may be that most “famous” athletes are men, and like any personal issue, some people choose to talk about their disease, while others do not.

Obviously, disclosure by public figures of personal battles with cancer is a very difficult decision. And as difficult as it may be for any man, celebrity or otherwise, to openly discuss his experience with TC, speaking out has created awareness, which saves lives. So lets thank all men who bravely fight this disease for their courage, and for sharing their courage with us, when they can.