PALO ALTO, CA — When men are diagnosed with localized prostate cancer, they are often faced with a difficult decision. Ascertaining patient preferences is critical, because radical prostatectomy, radiotherapy, and, in some cases, active surveillance have equivalent long-term cancer-specific outcomes, according to a new study.
“The risk profiles of each treatment option differ; therefore, shared decision-making is an important part of the prostate cancer treatment approach,” wrote a researcher from Stanford University and the VA Palo Alto Healthcare System. “Patients need to feel confident in understanding how the risks and benefits pertain to them. Given that all treatment options are associated with excellent prostate cancer-specific mortality rates,2 discussion of the potential adverse effects of surgical procedures and radiotherapy is especially important to help patients select treatment that best suits their goals.”
Still, according to the report in JAMA Network Open, updated information is needed on a key question: What is the long-term incidence and risk of second primary cancer after radiotherapy versus non-radiotherapy treatments. That might “help to inform discussions of risks and benefits for men diagnosed with prostate cancer,” the authors wrote.1
The study team sought to assess the current incidence and risk of developing a second primary cancer after receipt of radiotherapy versus non-radiotherapy treatments for prostate cancer.
Using the VA Corporate Data Warehouse, the study identified 154,514 male veterans 18 years and older who had localized prostate cancer (tumor stages T1-T3) diagnosed between Jan. 1, 2000, and Dec. 31, 2015, and no cancer history.
After patients were excluded for not meeting the full criteria, the remaining 143,886 patients had a median (IQR) follow-up of 9 (6-13) years. Data were analyzed from May 1, 2021, to May 22, 2022. The researchers focused on diagnosis of a second primary cancer more than 1 year after prostate cancer diagnosis.
Participants had a median age of 65, with 63.3% of them non-Hispanic white. More than 26% were Black of African American descent, 9% were of unknown race, and 5.1 were Hispanic or Latino, with smaller percentages of American Indian or Alaska Natives and Native Hawaiian or other Pacific Islanders.
About one-third of the patients, 52 886, received primary radiotherapy, while 91,000 did not. A second primary cancer more than one year after prostate cancer diagnosis was discovered in 3% of patients—3.7% in the radiotherapy cohort and 2.5% in the non-radiotherapy cohort.
After multivariable analyses, researchers advised that patients in the radiotherapy cohort had a higher risk of second primary cancer compared with those in the non-radiotherapy cohort at years 1 to 5 after diagnosis (hazard ratio [HR], 1.24; 95% CI, 1.13-1.37; P < .001), with higher adjusted HRs in the subsequent 15 years (years 5-10: 1.50 [95% CI, 1.36-1.65; P < .001]; years 10-15: 1.59 [95% CI, 1.37-1.84; P < .001]; years 15-20: 1.47 [95% CI, 1.08-2.01; P = .02).
“In this cohort study, patients with prostate cancer who received radiotherapy were more likely to develop a second primary cancer than patients who did not receive radiotherapy, with increased risk over time,” the authors concluded. “Although the incidence and risk of developing a second primary cancer were low, it is important to discuss the risk with patients during shared decision-making about prostate cancer treatment options.”
Background information in the articles point out that the risks associated with radical prostatectomy are well understood “because of the availability of many surgical outcomes’ data sets that cover the brief perioperative period, during which complications become apparent.”
“During radiotherapy, clinicians similarly assess patients for the presence of acute toxic effects and discuss symptom management,” the study added. “However, late toxic effects can present months to years after completion of radiotherapy, when patients may no longer regularly receive care from a radiation oncologist.”
The researchers noted that one late toxic effect, radiotherapy-induced cancer, specifically sarcoma occurring in previously irradiated bone, has been described for about 80 years. The phrase “second primary cancer” is used when cancer in patients who previously received radiotherapy cannot be clearly attributed to the procedure.
The study’s hypothesis was that the incidence and risk of developing a second primary cancer within the relevant anatomical field would be higher among patients who received primary radiotherapy compared with those who received non-radiotherapy treatments, including surgical procedures, active surveillance, medical management or observation, the authors wrote.
- Bagshaw HP, Arnow KD, Trickey AW, Leppert JT, Wren SM, Morris AM. Assessment of Second Primary Cancer Risk Among Men Receiving Primary Radiotherapy vs Surgery for the Treatment of Prostate Cancer. JAMA Netw Open. 2022 Jul 1;5(7):e2223025. doi: 10.1001/jamanetworkopen.2022.23025. PMID: 35900763; PMCID: PMC9335142
