Doctors in a new international study say they've found a way to detect early signs of testicular cancer before it starts to metastasize.1 What does that mean for patients? Physicians could use a simple screening test to diagnose the cancer that can potentially cause male infertility, say doctors in Denmark who reached their findings in a case study.
Doctors at Rigshospitalet in Copenhagen say they diagnosed the first case ever of pre-invasive testicular carcinoma in situ (CIS), a localized form of the cancer, in a semen sample collected from a 23-year-old man. The patient had been included in a separate study by the research team as a supposedly healthy individual with suspected infertility, but no suspicion of cancer.
A Dilemma for Cancer Patients
The incidence of boys and young men with testicular cancer who have future plans to begin a family is rising, experts contend. Yet in some cases, they say, the cancer itself and/or the treatment for it may have a negative impact on the patient's fertility.2
Testicular cancer affects an estimated 7,600 men in the United States each year. But when diagnosed early, this type of cancer is highly treatable.3 Nearly all testicular cancers begin in the testicles' germ cells, and develop into one of two varying types: seminomas and nonseminomas. The latter tends to grow and spread more quickly, but seminomas are more sensitive to radiation.
Risk factors for testicular cancer include having an undescended testicle, an abnormal development of a testicle, a family history of testicular cancer, a disease known as Klinefelter's syndrome, and being Caucasian.4
Once testicular cancer starts to spread, treatments such as chemotherapy and radiotherapy may be chosen, both of which can increase the risk of infertility.
Improving on Current Diagnostic Techniques
The method used to detect testicular cancer much earlier is an improvement over previous methods, said Christina Hoei-Hansen, MD, the study's chief investigator who is currently a PhD student. "In earlier studies, it was found that CIS cells could be found in semen samples of patients with testicular cancer," Hoei-Hansen said. "However, it was difficult and time-consuming to detect these CIS cells, and the methods were not sufficiently reliable to be used for diagnostic purposes in the clinic."
In an earlier study,5 Hoei-Hansen's team discovered a gene that produces a protein activated in testicular cancer. It is this protein that the researchers say can be used as a biological indicator of this cancer. The protein isn't normally active in men without testicular cancer, but is highly active when the cancer is present, "and it does not degrade substantially in semen," Hoei-Hansen explained.
An Unexpected Turn of Events
The 23-year-old man in this case study was participating in an unconnected infertility study involving several groups of male patients. Semen samples had been taken from a group with known testicular cancer and from several groups with other types of cancers and infertility problems, as well as a group of healthy men.
"When we were evaluating the first series of semen samples, we detected cells [positive for the protein] in a sample from one of the healthy controls," Hoei-Hansen recalled. "He was … having a routine semen analysis because he and his partner had been trying unsuccessfully for 18 months to have a baby."
Apart from the cells in the semen sample testing positive for the protein marker, there was no other sign of testicular cancer in this patient, the researchers noted. When a biopsy was performed, the cancer diagnosis was confirmed.
Doctors advised the patient to have his malignant testicle removed, freezing sperm samples beforehand. As a result, no chemotherapy or radiotherapy was necessary. Later, the patient and his partner successfully became pregnant, conceiving naturally.
Marking New Ground
"To our knowledge, this is the first report of the diagnosis of testicular cancer at the pre-invasive CIS stage in a semen sample from a young patient with suspected infertility who, if not for the inclusion in our study of [the protein marker], would most probably have been diagnosed much later, perhaps only after an overt tumor had developed," said Neils Skakkebaek, MD, head of the University Department of Growth and Reproduction at Rigshospitalet.
"The value of this method for diagnostic use in the clinic requires further, careful validation in a large series of patients and controls, but the preliminary results are promising," he said.
The test confirmed cancer in five of 12 patients in the study who had been suspected of having testicular cancer, and when the patient in the control group was added, it indicated the sensitivity of the test was about 46%, the researchers stated. There were no false-positives recorded.
If future trials confirm the validity of this testing method, "it could be offered in andrology and fertility clinics to young men at risk of testicular cancer because of atrophic testes, a history of cryptorchidism [undescended testicle], or who need assisted reproduction techniques," said Hoei-Hansen.
1. Hoei-Hansen CE, Rajpert-De Meyts E, Carlsen E, Almstrup K, Leffers H, Skakkebaek NE. A subfertle patient diagnosed with testicular carcinoma in situ by immunocytological staining for AP-2 {gamma} in semen samples: Case report. Hum Reprod 2005 Mar;20(3):579-82. Epub 2005 Jan 13.
2. Giwercman A, Petersen PM. Cancer and male infertility. Baillieres Best Pract Res Clin Endocrinol Metab 2000 Jun;14(3):453-71.
3. Mayo Clinic. Testicular Cancer. Available at: http://www.mayoclinic.com/invoke.cfm?id=DS00046. Accessed March 10, 2005.
4. National Cancer Institute. National Institutes of Health (NIH). General Information About Testicular Cancer. Available at: http://www.cancer.gov/cancerinfo/pdq/treatment/testicular/patient/. Accessed March 10, 2005.
5. Hoei-Hansen CE, Nielsen JE, Almstrup K et al. Transcription factor AP-2gamma is a developmentally regulated marker of testicular carcinoma in situ and germ cell tumors. Clin Cancer Res 2004 Dec 15;10(24):8521-30.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
