When cancer hits kids, parents are often faced with a horrible choice. Spare them the brutal chemotherapy and radiation and they die. Put them through it and they live — but often at a cost. There’s nausea, fatigue, hair loss and other side effects, for a time.
And there’s infertility, possibly forever.
Studies have long shown that cancer treatment can affect young patients’ ability to have children of their own later in life. Radiation can be particularly unforgiving to young reproductive systems. As a result, more and more young patients diagnosed with common childhood cancers such as leukemia, lymphoma, kidney cancer, bone cancer and neuroblastoma have been treated with less radiation and more intensive chemotherapy.
“The question is if you get only chemotherapy, is that still bad for you with regard to fertility and if so how bad?” said Dr. Eric Chow of Fred Hutchinson Cancer Research Center, lead author of a new study on survivorship and fertility. “This is the biggest study to look at that question specifically.”
Published Tuesday in Lancet Oncology, the new report sheds light on the degree to which chemo can impact the fertility of childhood cancer survivors and suggests steps young cancer patients (and their parents) may want to take before they receive treatment.
Chemo and fertility
Chow, who is also the medical director of the Cancer Survivor Program at Seattle Children’s Hospital, used data from more than 10,000 survivors in the Childhood Cancer Survivor Study and data on around 4,000 of the survivors’ healthy siblings — who served as “controls” — to figure out how chemo affected the survivors’ fertility. The Childhood Cancer Survivor Study, or CCSS, based at St. Jude Children’s Research Hospital, tracks kids who were diagnosed with common childhood cancers between 1970 and 1999.
Although treatment data was from before 2000, most of the 14 chemotherapy drugs examined by the team of researchers are still commonly used, Chow said.
How did these chemo drugs, most of them alkylating agents that damage DNA to keep cancer from growing, impact fertility?
The findings were mixed.
Women who’d had cancer as kids fared better, for the most part. Seventy percent of survivors had had kids by the age of 45 compared to 80 percent of their healthier sisters. But there was one caveat: Women who waited until they were over 30 had a slimmer chance of getting pregnant.
“We’re not saying women have to have kids early but that people need to be aware that this and other studies suggest that even if overall, the impact on fertility is relatively minor, women do seem to be at higher risk of earlier menopause,” said Chow. “Women who had not yet had kids by age 30 were substantially less likely to have kids than cancer survivors who decided to get pregnant earlier, and also much less likely than siblings who had not had kids by age 30.”
The news for male childhood cancer survivors was not as promising.
Men who’d survived cancer as kids were significantly less likely to father children if treated with chemo (particularly regimens containing high doses of alkylating drugs and cisplatin). Only 50 percent of male survivors reported they’d fathered a child (or got a partner pregnant) by age 45 compared to 80 percent of the control group.
Overall, Chow said he believed the news was positive.
“We think these results will be encouraging for most women who were treated with chemotherapy in childhood,” he said. “However, I think, we as pediatric oncologists still need to do a better job discussing fertility and fertility-preservation options with patients and families upfront before starting cancer treatment.
“In particular, all boys diagnosed post-puberty should be encouraged to bank their sperm to maximize their reproductive options in the future,” he advised. “The current options for post-pubertal girls remain more complicated, but include oocyte [egg] and embryo cryopreservation.”
Chow said sperm banking for pre-pubescent boys in the conventional sense is not possible, but said investigational approaches were being developed.
The pre-treatment talk
When Daniel Bral was diagnosed with non-Hodgkin lymphoma, he certainly wasn’t thinking about starting a family. He was 11. Sixteen years after that diagnosis, however, fertility is now becoming more relevant.
“I’m sort of at the ignorance-is-bliss stage,” said Bral, 27, now a medical student and chairman of the Young People’s Advisory Committee for Teen Cancer America. “I don’t want to know, because I’m not sure I can handle knowing that I can’t have children and I was never given the opportunity to prevent that.”
Bral, who was not offered fertility preservation options when he was diagnosed, said Chow’s study brings up a “really important question.”
“It’s an issue that’s even more important in teen and young adult cancer treatment, a demographic which may not have fertility and childbearing at the forefront of their consciousness,” he said. “Health care providers need to become more comfortable with having the conversations frankly with their patients.”
Unmarried and currently living in Ft. Lauderdale, Bral said he does wonder about his fertility status.
“As a man who is excitedly looking forward to having children and a family of my own, it’s a sensitive and difficult topic to deal with head-on,” he said. “It does bother me on some level that I may have had my fertility impacted although again, I’m not sure to what extent, if at all, it’s been affected.”
Chow said parents of recently diagnosed teens should definitely talk to their child’s health care team about options.
“It’s hard to do anything if you’ve already started treatment,” he said. “But if you have questions, your oncology team should be able to talk to you about it and make recommendations. At Seattle Children’s, we have a group that will help patients and families with fertility preservation options. This is also a topic we bring up with patients and families after they’ve finished treatment and we’re seeing them now in our cancer survivor clinic.”
He also suggested female survivors may want to start thinking early about whether or not they want children.
“The general take-home message for women who’ve had cancer as children is if they want to have kids, it’s probably not a bad idea to talk with a reproductive fertility specialist earlier rather than later,” he said. “Especially if they’re thinking about delaying childbirth to their mid- or late 30s. Not everyone should go out and freeze their eggs — that’s expensive — but they should be aware that their window of fertility may be smaller after having cancer treatment.”
Caveats and questions
Along with Fred Hutch, Seattle Children’s and St. Jude (Fred Hutch is the data and statistics center for the CCSS), the study involved researchers from Memorial Sloan Kettering Cancer Center, Stanford University, the Children’s Hospital of Philadelphia, Boston Children’s Hospital, Columbia University and MD Anderson Cancer Center. Study participants came from 27 cancer treatment centers across the U.S. and Canada.
Chow readily acknowledged the report’s limitations.
It relied on self-reported data regarding pregnancy from both patients and their siblings, for instance. And it didn’t take into consideration whether the study participants were actually trying — and failing — to become pregnant or not.
“Having children is a complicated thing,” he said. “You have to want kids, number one. And you have to have a partner, typically. And those are things we weren’t able to measure. It’s certainly possible that the reduced rate of pregnancy seen in women ages 30 to 45 may be related to issues other than ovarian function.”
The amount of chemo given a particular patient also posed new questions, he said.
Men who’d been given high cumulative doses of alkylating agents such as cyclophosphamide, ifosfamide and procarbazine — along with the agent cisplatin — were linked with a significantly reduced likelihood of fertility. Previous studies have suggested these drugs lower sperm count and reduce testicular volume.
“We identified a strong association between cisplatin and reduced fertility in male survivors which will need to be studied further,” Chow said, adding that this finding may influence guidelines.
"This could have an effect on guidelines on screening survivors for fertility-related issues, with regards to chemotherapy dose thresholds that are associated with higher risk of fertility-related issues," he said. "I think these results also will stimulate more research into the effects of some of these newer agents on a biologic/physiologic level, especially in relation to spermatogenesis [sperm-cell development] and male fertility."
Fertility preservation options for prepubescent kids also needs further investigation, the researchers said.
Diane Mapes is a staff writer at Fred Hutchinson Cancer Research Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor and patient advocate, she writes the breast cancer blog doublewhammied.com and tweets @double_whammied. Reach her at dmapes@fredhutch.org.
