| The Testicular Cancer Resource Center |
Wouldn't it be nice if we could think of our cancer as a one-time experience? Once you were through, you could say that you had been there, done that, and at least you would never have to deal with cancer again. I know I used to think that way. I had already had my cancer. Surely I had already had my turn.
Unfortunately, life does not work that way. Cancer survivors as a group are more likely to develop a new primary cancer than people who have never had cancer. Sometimes that second cancer is related to the treatment used to cure the first one. Sometimes there may be genetic, biological, environmental, or lifestyle factors that increase the risk of more than one cancer. And sometimes it is simply another cancer that would have occurred anyway. Whatever the reason, having had one cancer unfortunately does not mean you have already had your turn.
A second primary cancer is a completely new cancer. It is not a recurrence of the original testicular cancer and it is not testicular cancer that has spread somewhere else. Most testicular cancer survivors will never develop a treatment-related second cancer, but the risk is real, and some of it can persist for decades.
A new cancer in the remaining testicle is a special case. Men who have had testicular cancer have a much higher relative risk of developing another testicular cancer than men who have never had the disease, but the absolute risk is still fairly small. Large studies generally put the risk at about 2% over 15 years, with some estimates reaching 2-3% with longer follow-up.
This increased risk does not appear to be caused by chemotherapy or radiation. It is thought to reflect the same underlying susceptibility that contributed to the first testicular cancer. A cancer in the other testicle is therefore a new primary cancer, not a recurrence of the first one.
The TCRC recommends continuing a monthly testicular self-exam of the remaining testicle and having any new lump, enlargement, firmness, or other persistent change evaluated promptly.
Radiation therapy has the clearest long-term association with second solid cancers after testicular cancer. The greatest risk is in organs that were in or near the radiation field, including parts of the stomach, pancreas, bowel, bladder, and kidneys. These cancers usually do not appear right away. The increased risk becomes more important many years after treatment and can persist for decades.
Much of what we know comes from men treated years ago, when radiation fields were larger and doses were often higher. Prophylactic radiation to the chest is no longer part of routine testicular cancer treatment, and modern radiation for seminoma uses smaller fields and lower doses. That should reduce the risk, but because second solid cancers may take 10, 20, or more years to appear, it takes a very long time to know the full effect of changes in treatment.
Most chemotherapy for testicular cancer is given as a combination such as BEP (bleomycin, etoposide, and cisplatin) or EP (etoposide and cisplatin). Two of those drugs, etoposide and cisplatin, have been associated with an increased risk of later cancers.
Etoposide has a particularly well-established, dose-related association with treatment-related leukemia, especially acute myeloid leukemia (AML). The absolute risk is small with the cumulative doses normally used in standard first-line treatment, but it rises as the total dose of etoposide increases. Cisplatin has also been associated with an increased risk of leukemia, and long-term studies suggest that cisplatin-based chemotherapy modestly increases the risk of some solid cancers many years later.
Treatment-related leukemia tends to occur earlier than treatment-related solid tumors, usually within the first several years after chemotherapy. Solid cancers generally have a much longer latency and may not appear until 10 or more years after treatment.
Men who received both chemotherapy and radiation appear to have the greatest overall risk of a later non-germ-cell cancer. This is one reason doctors try to avoid unnecessary treatment and unnecessary additional cycles of treatment.
Men managed with orchiectomy, surveillance, or surgery such as RPLND avoid the known cancer-causing effects of chemotherapy and therapeutic radiation. A recent large review found no increase in non-germ-cell second cancers after surgery alone, although individual studies have not been completely consistent. In other words, the evidence is reassuring, but it would be too strong to say that testicular cancer survivors on surveillance have exactly the same lifetime cancer risk as everyone else.
Surveillance itself is also not completely radiation-free. CT scans use ionizing radiation, and older surveillance schedules could expose a young man to a substantial number of scans over several years. That radiation exposure is far smaller than a course of radiation therapy, but it is still real and it accumulates. Modern surveillance schedules generally use fewer CT scans, lower-dose techniques when appropriate, and MRI in some settings specifically to reduce radiation exposure.
Hopefully this problem will continue to shrink. New blood markers such as miR-371a-3p (miR-371) may eventually allow doctors to reduce surveillance imaging even further. The marker is very promising, but it is not yet a complete replacement for imaging and it does not reliably detect teratoma.
The original version of this TCRC page was based largely on studies published by Travis and colleagues in 1997 and 2005. Those studies were important because they clearly demonstrated that curing testicular cancer can have consequences many years later. They also reflected many men who had been treated with chemotherapy regimens and radiation practices that are no longer commonly used.
The basic lesson has held up remarkably well: do what is necessary to cure the cancer, but do not use more treatment than is necessary. Modern testicular cancer treatment increasingly tries to accomplish exactly that. More men with Stage I disease are managed with surveillance, chemotherapy is given in defined and relatively short courses, radiation is used much less often, and radiation fields and doses have been reduced.
None of this means that someone who needs chemotherapy or radiation should avoid it because of a possible cancer decades in the future. The first job is to cure the testicular cancer. The goal is to do that while avoiding treatment that does not improve the chance of cure.
There is no special blood test or scan that can screen a healthy testicular cancer survivor for every possible second cancer. After the usual testicular cancer follow-up is complete, survivors should continue regular primary care and the same age- and risk-appropriate cancer screening recommended for everyone else.
Formal testicular cancer follow-up eventually ends for most patients. Survivorship does not. Long after the tumor markers and routine scans stop, it still makes sense to have regular medical care and to make sure future doctors know that you were treated for testicular cancer and exactly how you were treated.
Selected Sources and Further Reading: