Testicular nonseminoma (NSGCT)

The testicles make sperm and the hormone testosterone. Almost all testicular cancers start in germ cells, the cells that make sperm. The U.S. National Cancer Institute (NCI) says there are two main types of these germ cell tumors, seminoma and nonseminoma, and they grow and are treated differently. Nonseminomas tend to grow and spread more quickly than seminomas.

Nonseminoma is a family of cell types: embryonal carcinoma, yolk sac tumor, choriocarcinoma and teratoma. Most nonseminomas are a mix of these. A tumor with any nonseminoma part, even if it also has seminoma, is treated as a nonseminoma. So is a tumor that looks like pure seminoma under the microscope but comes with a raised blood level of alpha-fetoprotein (AFP). Pure seminomas do not make AFP.

Doctors group the cancer by stage, which shows how far it has spread. When it has spread, they also use an international risk system (the IGCCC). It sorts men into good, intermediate or poor prognosis groups. The groups are based on where the cancer has spread, how high the blood tumor markers are, and whether the tumor started in the chest rather than the testicle.

The exact cause is not known. NCI lists several risk factors. They include an undescended testicle (cryptorchidism), a testicle that is small or does not work normally, and testicular carcinoma in situ. Others are a personal or family history of testicular cancer, Klinefelter syndrome, and being a White man. A family history counts especially when it is a father or brother. Testicular cancer can also develop in men with none of these risk factors.

Researchers at the International Agency for Research on Cancer (IARC) say an undescended testicle raises the risk about four times. NCI says surgery to correct it before puberty appears to lower the risk, but this is not certain.

Rates differ around the world and have changed over time. IARC reports that testicular cancer has become more common in many countries since the 1950s, and says changes this fast point to environmental or lifestyle causes. No clear way to prevent it has been found. In 2020, rates were highest in Western, Northern and Southern Europe and in Oceania, and lowest in Asia and Africa.

Signs include a painless lump or swelling in either testicle, a change in how the testicle feels, or a dull ache in the lower belly or groin. Some men notice a sudden build-up of fluid in the scrotum, or pain in a testicle or the scrotum. These signs can also have other causes.

Staging follows the usual path of spread. First come nearby lymph nodes at the back of the belly (the retroperitoneum). Next come distant lymph nodes and the lungs. Less often, the cancer reaches other organs such as the liver, bones or brain. Spread to organs other than the lungs, very high tumor markers, and a tumor that started in the chest are the main signs of a harder-to-treat cancer.

Even so, NCI says men whose cancer has spread widely, including to the brain, may still be cured and are treated with that aim. Most men with nonseminoma that has spread fall into the good-prognosis group.

Treatment can affect fertility. Chemotherapy, RPLND and radiation can each cause infertility. So men can be offered the chance to bank sperm before any treatment beyond removing the testicle. Still, in two large studies about 70% of men fathered children after treatment. NCI notes that men are advised to wait at least 3 months after chemotherapy before conceiving a child, unless they use sperm banked beforehand.

Follow-up lasts for years. Surveillance after stage I means regular visits with blood tumor markers, chest X-rays and CT scans. In one common schedule, visits are monthly in the first year and then less often, for 10 years in total. A clear rise in AFP or hCG is often the first sign of a relapse. Men who have had testicular cancer have about a 2% chance of cancer in the other testicle over the next 15 years.

Chemotherapy can have lasting effects. Cisplatin can cause some hearing loss, usually at high pitches outside the range of normal speech, and a small drop in kidney function. Bleomycin can affect the lungs. Survivors who had chemotherapy or radiation have a higher risk of heart disease and second cancers. Chemotherapy has also been linked with metabolic syndrome and low testosterone. So long-term check-ups matter. High-dose chemotherapy carries more risk: in a report of 364 men treated at Indiana University from 2004 to 2014, 9 died from treatment-related causes and 5 later developed leukemia.

No donor is involved in treating testicular nonseminoma. Most men are cured with surgery, chemotherapy or both, and never need a stem cell transplant.

When high-dose chemotherapy is used for cancer that comes back or does not respond, the stem cells are the man's own. They are collected, usually from his blood, before treatment. They are frozen and given back afterward to rebuild the blood-forming cells that the high doses destroy (autologous stem cell rescue). Often two rounds are given one after the other, called a tandem transplant. In the United States and Canada, 77% of these transplants reported to the CIBMTR registry in 2010 to 2015 were tandem.

EBMT's 2025 recommendations list only the own-cell transplant for adults with germ cell tumors, and NMDP's consultation guidance for germ cell tumors describes only autologous stem cell support. People who join a blood stem cell registry help patients with other conditions, such as leukemia, who need a donor's cells.