Patients with localized prostate cancer seemed to have a lower risk of developing subsequent primary cancers when treated with carbon-ion radiotherapy (CIRT) versus photon beam radiotherapy (RT) or surgery, according to researchers from Japan.
Based on a propensity score-weighted analysis, CIRT was associated with a hazard ratio of 0.81 (95% CI 0.66-0.99, P=0.38) compared with photon beam RT, and an HR of 0.81 compared with surgery (95% CI 0.68-0.95, P=0.0088), reported Hirokazu Makishima, MD, of the National Institute of Radiological Sciences (NIRS) in Chiba, and colleagues.
In contrast, photon beam RT was associated with a higher risk of subsequent primary cancer (HR 1.18, 95% CI 1.02-1.36, P=0.29), they wrote in Lancet Oncology.
The findings could have safety implications for prostate cancer patients in an era of younger-age diagnosis and expanding life expectancy. In addition, charged-particle therapy is thought to achieve better dose distribution and higher biological effectiveness than photon radiotherapy. The heavy ion and larger mass of carbon has the potential to lead to deeper tissue penetration and efficacy in hypoxic tumors, the authors explained.
The study observed a cumulative incidence of subsequent primary cancers (mainly abdominopelvic solid tumors) at 9.9 years’ follow-up of 16.1% (95% CI 13.9-18.4) in the CIRT group, 24.0% (95% CI 20.5-27.6) in the photon beam RT group, and 18.7% (95% CI 17.4-20.1) in the surgery group.
“Although prospective evaluation with longer follow-up is warranted to support these results, our data supports a wider adoption of carbon ion radiotherapy for patients with expected long-term overall survival or those with poor outcomes after receiving conventional treatments,” the authors stated.
The retrospective study drew on the records of patients receiving CIRT for prostate cancer from June 1995 to July 2012 at the NIRS, and from control cohorts of prostate cancer patients receiving photon RT or surgery in the Osaka Cancer registry from January 1994 to December 2012. It excluded those with metastasis, node-positivity, locally invasive prostate cancer, prior synchronous malignancies, and previous RT or chemotherapy.
In the NIRS cohort, 1,455 eligible patients (median age 68) received CIRT, a modality introduced in Japan in the 1990s. In the Osaka Registry, 1983 patients (median age 71) received photon beam RT, and 5,948 patients (median age 68) had surgery. The median follow-up in the three treatment groups was 7.9 years, 5.7 years, and 6.0 years, respectively. More than half in the CIRT cohort had the risk factor of being current or former smokers.
In the CIRT group, 218 (15%) developed a total of 234 subsequent tumors. The most common primary malignancies were stomach (19%), lung (17%), colon (12%), and bladder (9%), with a median time to first subsequent primary cancer of 5.7 years. Risk factors for these later tumors were increased age and smoking.
“This hypothesis-generating study requires further validation in prospective studies, or from additional multinational datasets, in disease sites other than prostate cancer, especially in the setting of similar proton data,” Makishima’s group wrote.
Study limitations included its observational nature, the heterogeneous use of external beam and brachytherapy in the photon beam RT group, and the lack of details on dose fractionation and field design. In addition, the Osaka registry did not collect data on potential risk factors such as smoking, alcohol consumption, family history of cancer, and other comorbidities, thereby limiting the study’s propensity-score covariates.
Furthermore, despite Japan’s universal healthcare care coverage, it is possible that CIRT recipients were of higher socioeconomic status, and possibly healthier than the two control groups. Also, more patients in the surgery group may have undergone endoscopic surveillance, which is uncommonly done for radiation oncology patients, the authors noted.
The study did not allow for the usual latency periods for developing hematologic and solid tumors, and with a maximum follow-up period of only 10 years, the results could not reflect the likely increase in cancers in all cohorts over time. Additionally, selection bias may also have impacted the results since the NIRS patients came from all over Japan and not from a single prefecture like the Osaka cohort. Another potential confounding bias might have stemmed from different follow-up start times across the three cohorts.
Howard M. Sandler, MD, of Cedars-Sinai Medical Center in Los Angeles, told MedPage Today that the findings were “encouraging.” He said that while there is considerable interest in developing them, there are currently no CIRT centers in the U.S., “so these findings would have no immediate impact on practice here.”
Sandler, who was not involved in the study, added that CIRT facilities would be more expensive because, apart from start-up costs, the heavy cyclotron-charged particles require a much larger facility even than proton beam RT.
He also pointed out that, despite the CIRT findings, “there is still no proof that this technology is better. The widespread adoption of [CIRT] will only happen if studies show it is more effective. And in an era when we try to keep healthcare costs down, it will have to be not only more effective, but also cost-effective. It will have to add value to the healthcare system.”
In an accompanying commentary, Charles N. Catton, MD, and David B. Schulz, MD, PhD, both of the Princess Margaret Cancer Centre in Toronto, said the study’s most important contribution was increasing awareness of radiation-related second malignancies after prostate radiotherapy. The findings should not, however, “encourage a general move from photon radiotherapy for those who choose radiotherapy for their prostate cancer.”
This study was funded by Japan’s Research Project for Heavy Ions at the National Institutes for Quantum and Radiological Sciences and Technology.
Makishima and co-authors, Catton and Schultz, and Sandler, disclosed no relevant relationships with industry.