Helping Patients Understand Secondary Cancer Risk
Patients who receive certain cancer treatments are at greater risk of secondary malignancies and must be educated accordingly.
Secondary malignancies comprise 19% of all cancer diagnoses in the US.
The 1945 atomic bombings in Japan left instantaneous death and destruction, but it wasn’t until years later that the devastating lasting effects began to appear in the population. At first, leukemia from radiation exposure was diagnosed among bombing survivors. Then, cases of solid cancers, such as bladder, breast, colon, lung, and thyroid, emerged.1
Although the scientists who created the atomic bomb understood the increased risk of cancer from radiation exposure, this wasn’t common knowledge to the average person. Still, today, with the known risks, radiation is routinely used to treat many types of cancer. Furthermore, chemotherapy, chimeric antigen receptor (CAR) T-cell therapy, and certain targeted therapies are also some of the best ways to eradicate cancer cells that are growing inside of a person’s body despite the possibility that these treatments may lead to the formation of secondary cancer.2
Double-Edged Sword
The development of a new cancer following primary cancer treatment is called secondary malignancy, and these account for 19% of all cancer diagnoses in the United States.3
In addition to the type of primary cancer treatment used, other risk factors for secondary cancers include environmental exposures, genetics, and lifestyle choices.2 For instance, sun exposure, smoking, and alcohol use may play a role in secondary malignancy development, says Megan Wanca, APRN, DNP, FNP-C.
However, one of the most significant risk factors is radiation therapy. The dosage and length of time and frequency it was given can affect a patient’s secondary malignancy risk.2 For example, sarcomas are more common in areas that received higher doses of radiation or areas that were near the treatment site.Carcinomas, leukemias, mesotheliomas, and myelodysplastic syndromes (MDS) are also associated with radiation therapy. Typically, leukemias appear within 10 years of initial treatment, but solid tumors may occur 10 years or later.2,3
Certain organs, such as the breast and thyroid, have a higher risk for developing cancers after radiation exposure compared with other organs.2
Moreover, a patient’s age at the time of radiation therapy may influence later cancers. If a patient receiving radiation treatment to the chest for Hodgkin lymphoma is closer to menarche, she may be at an increased risk of radiation therapy–induced breast cancer. However, if she is closer in age to menopause, that patient’s breast cancer risk may be decreased.3
Secondary esophageal, lung, kidney, thyroid, contralateral breast, and uterine cancers, as well as lymphomas and leukemias, can be seen in patients with breast cancer who were treated with radiation therapy. Specifically, breast cancer survivors who smoke have a significant increase in the risk of ipsilateral second lung cancer.3
A meta-analysis of 13 clinical trials that included more than 760,000 patients with breast cancer showed an association between breast cancer radiation therapy and an increased risk of a second nonbreast cancer more than 5 years after primary cancer treatment.4
Men treated with external beam radiation therapy for prostate cancer also have a higher cumulative incidence of secondary cancer compared with those who were treated with radical prostatectomy, according to study findings published in Scientific Reports. The researchers examined the risk in more than 7600 men and observed an increased risk of genitourinary and lung cancers in these men more than 5 to 15 years post-treatment.5
“Just like with radiation, the risk of secondary malignancy increases with higher doses of chemotherapy, longer treatment time, or higher intensity of the dosing,” says Wanca, who is a hematology/oncology nurse practitioner at Vanderbilt University Medical Center in Nashville, Tennessee.
Chemotherapy-related secondary malignancies include leukemias, such as acute myeloid leukemia (AML) and acute lymphoblastic leukemia, and MDS. Certain chemotherapies such as alkylating agents, platinum-based drugs, and anthracycline topoisomerase II inhibitors put patients at greater risk.2
The Childhood Cancer Survivor Study, which included more than 25,000 survivors, observed the risk of developing leukemia to be 6 times greater in survivors compared with the general population. The retrospective cohort study showed that 77 survivors developed subsequent leukemia—49 survivors received a diagnosis of late leukemia with a median time of 7.8 years after treatment, and 28 survivors received a diagnosis of very late leukemia with a median of 25.4 years later. AML, MDS, and chronic myeloid leukemia were the most common leukemia subtypes seen. Moreover, an epipodophyllotoxin dose greater than 4000 mg/m2 was associated with an increased risk for these leukemias.6
New treatment options, such as targeted and CAR T-cell therapies, pose a small risk for secondary cancers. Vemurafenib (Zelboraf) and dabrafenib (Tafinlar), which target BRAF, are known to have a higher risk of squamous cell carcinomas.2
In recent years, a clinical trial and a report investigated whether CAR T-cell therapy caused secondary T-cell lymphomas. The one investigation, published in The New England Journal of Medicine, analyzed the case of a patient with multiple myeloma who had been treated with ciltacabtagene autoleucel (Carvykti). The investigators found evidence of a CAR gene in the T-cell lymphoma cells along with other genetic alterations and concluded that the CAR T-cell therapy likely contributed to the second cancer.7
However, more long-term data is needed to get a clear understanding of the secondary malignancy risk that may stem from these treatments, explains Wanca.
Risk Versus Reward
Radiation, chemotherapy, targeted therapy, and CAR T-cell therapy have risks, but they are helping patients live longer every day. There are benefits and risks in every situation, but the crucial part is ensuring patients and caregivers are as informed as possible to weigh the pros and cons for themselves, says Johnny Rollins, MSN, APRN, ANP-C, who is associate director of Advance Practice Programs—Survivorship and a thyroid cancer survivorship provider at The University of Texas MD Anderson Cancer Center in Houston, Texas.
When creating a cancer treatment plan, oncology nurses and advanced practice providers (APPs) explain the drug that will be used and its adverse effects (AEs) to the patient. Treatment goals can be very individualized, explains Rollins.
“Some patients have upcoming plans that they want to be involved in, and it’s important for nurses to connect with their patients and understand what their goals are to help them achieve those goals,” says Rollins. “Oncology nurses hold a crucial role in helping patients navigate their cancer journey. Patients get that big ‘c’ word in front of them, and their eyes can just glaze over. It’s important for the nurses to take that time and let the patients and their caregivers ask questions.”
Education is one of the most powerful tools for a patient, and this can come directly from their nursing team. For instance, provide patients and their caregivers with an evidence-based information sheet that they can bring home. Oncology nurses and APPs can also encourage patients to sit with the information, ask questions, and take their time in treatment decision-making so they can understand all the risks and AEs.
“It may involve multiple visits and multiple messages but let them experience the emotions and we can talk them through [them],” says Wanca. “Every day I get to be with patients on some of their darkest days. I don’t think fear should outweigh the benefit of getting the primary treatment.”
Both Rollins and Wanca can’t stress enough the importance of making sure patients and survivors have a caregiver present. It can be a spouse, partner, family member, or friend. But really, it’s having another set of eyes and ears to absorb the information being provided. In some cases, a patient may want to keep their disease a secret or at other times a caregiver wants a different treatment plan to be considered, explains Rollins. “One of our most basic, essential roles is educating [them] and having the patient and caregiver on the same page,” he says.
Encourage Mindful Monitoring
To help mitigate secondary cancer risk and monitor survivors, nurses and APPs should help patients schedule surveillance follow-up appointments. At those appointments, providers can perform physical exams and conduct imaging and blood tests to investigate for any signs or symptoms of new cancer development.
It helps to have a good survivorship clinic, explains Rollins, who also manages the Thyroid Cancer Survivorship Clinic at MD Anderson. The oncology teams at this institution use a tool called the MD Anderson Symptom Inventory, which is a patient-reported outcome measure. Each clinic’s questionnaire has specific questions related to its type of cancer and help nurses and APPs identify the severity of symptoms experienced by patients and how they may be affecting their quality of life. From there, patients can be referred to the treating oncologist or to a new clinic depending on the type of symptoms they’re experiencing, says Rollins.
“I often joke with my patients and tell them it’s much better for you to identify the cancer before your body tells you that you have it,” he says. “Having those colonoscopies, especially if you have a family history, mammograms, prostate screening, and skin exams for everyone is so important.”
The easiest way to monitor for cancer, whether it be primary or secondary, is to ensure that a patient visits a primary care doctor every year for a physical. “Blood work and blood pressure and glucose monitoring can give us so much information to help potentially block or slow down risk for patients,” says Rollins.
Nurses and APPs can also teach survivors to look for new moles or skin lesions. On sites where the body has had previous radiation, patients can watch for lumps or pain.8
Patients who are at a greater risk of cancer because of their family history should continue their annual screenings. This includes those who have hereditary cancer syndromes, such as BRCA 1/2, Lynch syndrome, or Li-Fraumeni syndrome.
To lower the risk of second cancers, scientists continue to research safer ways to deliver radiation. In Hodgkin lymphoma, low-dose radiation and highly conformal involved-node radiation therapy can help limit the size of the radiation field to just the involved lymph node, decreasing the radiation exposure to other organs. Similarly, stereotactic radiation therapy can provide high doses of radiation to just the tumor.3
Antiestrogen therapy can reduce the risk of secondary cancers in women who received breast radiation at an early age and the risk of lung cancer in older women.3
Release and Recharge
With so many different cancer types and novel therapies being approved by the FDA, sometimes the biggest challenges oncology nurses and APPs face when looking out for secondary cancers is keeping up to date with all the new developments, says Wanca.
“Immunotherapies, CAR T-cell therapies, bispecific therapies, and targeted therapies are coming out and hoping to reduce that adverse risk profile and mitigate future and long-term AEs, so consuming all of this and making it understandable for our patients is crucial,” she says.
Although oncology nurses put patients’ needs first, the burnout that they experience from working with oncology patients is significant. Nurses experience loss, recurrence, and secondary malignancies in patients with whom they have developed bonds.
“If you have a clear mind, you’re able to focus and concentrate. If we don’t have that emotional release, where we can recharge our emotional batteries, it can be difficult,” says Rollins. “When you’re having a tough day, finding that outlet, someone to talk to, where you can decompress will help us continue to do our best work.”
References
- Little MP. Cancer and non-cancer effects in Japanese atomic bomb survivors. J Radiol Prot. 2009;29(2A):A43-59. doi:1088/0952-4746/29/2A/S04
- Second cancers related to treatment. American Cancer Society. February 1, 2020. Accessed January 25, 2025. https://www.cancer.org/cancer/survivorship/long-term-health-concerns/second-cancers-in-adults/treatment-risks.html
- Khanna L, Prasad SR, Yedururi S, et al. Second malignancies after radiation therapy: update on pathogenesis and cross-sectional imaging findings. Radiation Oncology. 2021;41(3):876-894. doi:10.1148/rg.2021200171
- Poland S, Ebina W, Muggia F, Guth A. Breast radiation-associated secondary malignancies: a review. Clin Surg Oncol. 2023; 2(1):100010. doi:10.1016/j.cson.2023.100010
- Tiruye T, David R, O’Callaghan M, et al. Risk of secondary malignancy following radiation therapy for prostate cancer. Sci Rep. 2023;13:20083. doi:10.1038/s41598-023-45856-z
- Ghosh T, Hyun G, Dhaduk R, et al. Late subsequent leukemia after childhood cancer: a report from the Childhood Cancer Survivor Study (CCSS). Cancer Med. 2024;13(20):e70086. doi:10.1002/cam4.70086
- Phillips C. Understanding the risk of second cancers after CAR T-cell therapy. National Cancer Institute. August 13, 2024. Accessed January 25, 2025. https://www.cancer.gov/news-events/cancer-currents-blog/2024/car-t-cell-therapy-second-cancers
- Demarco C. Secondary cancers: why they occur and how to catch them early. The University of Texas MD Anderson Cancer Center. January 6, 2022. Accessed January 25, 2025. https://www.mdanderson.org/cancerwise/secondary-cancers--why-they-occur-and-how-to-catch-them-early.h00-159536589.html
