BERKELEY, CA (UroToday.com) - In this case report, we discussed the case of a high-grade undifferentiated sarcoma of bone diagnosed 6 years following prostate brachytherapy implant. The following were some additional concepts not fully expressed in the abstract.
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Historically, radiation has been linked to the development of secondary malignancies (SM). Various studies have conflicting results in regards to the risk of SM following prostate radiation therapy (RT). This is likely as it is almost impossible to distinguish between the potential risks of a RT-induced SM or a new primary, based on genetics, lifestyle factors, or more intensified surveillance. Furthermore, it is challenging to apply older studies to the current practice of radiation oncology which uses more sophisticated, conformal RT techniques. Several studies do report that RT may increase the long-term risk of SM in comparison to those who do not receive RT.[1, 2, 3, 4] A review of literature from the mid 1980s to January 2007 revealed that, although SMs after RT were found to be increased in some studies, after age adjustment and correction for follow-up duration there was no clear increase. The authors concluded that the high heterogeneity of the results implies that the risk of SM after prostate RT is inconclusive. In the modern treatment era it has been observed that SM rates after prostate RT were not different from the cancer incidence rates after radical prostatectomy (RP) when adjusted for patient age and smoking history. Despite this, further evidence in support of RT associated SM comes from a recent study by Nam, et al. which reported an increased risk of SM in patients treated with RT compared to RP. This relationship held true when analysis was limited to contemporary RT suggesting that, despite modern treatment techniques a notable risk of SM still exists. This study was adjusted for age, but not smoking history which limits its applicability to the general population given smoking is a well established risk factor for a variety of malignancies.
Given the relative novelty of brachytherapy (BT) there is less published about the risk of SM and the available evidence is conflicting. However, in general based on dosimetry, radiobiology, and clinical experience, the rate of SM is felt to be lower in BT in comparison to external beam radiotherapy (EBRT). A study by Moon, et al. reported that patients treated with EBRT had significantly higher odds of developing SM, however those treated with BT did not have significantly different odds of SM in comparison to those who did not receive RT. A large single-institution study by Hamilton, et al. similarly concluded that after adjusting for age and smoking history there were no differences in the SM incidence in a BT and RP cohorts compared with the cancer incidence in the general population. In contrast, another analysis reported an increased SM risk after BT for patients ≤ 60 and in the first 4 years of follow-up. These studies demonstrate the inconclusive nature of BT inducing SM. With respect to sarcomas, RT appears to be associated with an increased risk of developing a sarcoma, especially among younger patients. Evidence with less conformal treatment techniques report the increased risk of a sarcoma after RT as high as 145% at ≥ 5 years after diagnosis. One study reported sarcomas as representing 2% of the SM after RT, however the greatest percentage was observed amongst those receiving BT.
Most research has focused on SM rates after EBRT with variable results. There are limited studies that have examined the rate of SM following BT given the long latency time between radiation and development of malignancies as well as the short follow-up period available for a BT cohort. Furthermore, the risk of prostate RT-induced sarcomas is relatively undetermined partially owing to the low incidence of sarcomas in the general population. Thus, the contribution of prostate BT to the risk of SM, specifically sarcomas, remains unclear.
- Moon K, Stukenborg GJ, Keim J, Theodorescu D. Cancer incidence after localized therapy for prostate cancer. Cancer. 2006 Sep 1;107(5):991-8.
- Adel-Wahab M, Reis IM, Hamilton K. Second primary cancer after radiotherapy for prostate cancer – a SEER analysis of brachytherapy versus external beam radiotherapy. Int J Radiat Oncol Biol Phys. 2008;72:58–68.
- Brenner DJ, Curtis RE, Hall EJ, Ron E. Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery. Cancer. 2000;88(2):398-406.
- Virtanen A, Pukkala E, Auvinen A. Incidence of bone and soft tissue sarcoma after radiotherapy: a cohort study of 295,712 Finnish cancer patients. Int J Cancer. 2006;118(4):1017-21.
- Müller AC, Ganswindt U, Bamberg M, Belka C. Strahlenther Onkol. Risk of second malignancies after prostate irradiation? Strahlenther Onkol. 2007 Nov;183(11):605-9.
- Zelefsky MJ, Housman DM, Pei X, Alicikus Z, Magsanoc JM, Dauer LT. Incidence of secondary cancer development after high-dose intensity-modulated radiotherapy and image-guided brachytherapy for the treatment of localized prostate cancer. Int J Radiat Oncol Biol Phys. 2012;83:953–9.
- Nam RK, Cheung P, Hnerschorn S, Saskin R, Su J, Klotz LH, Chang M, Kulkarni GS, Lee Y, Kodama RT, Narod S. Incidence of complications other than urinary incontinence or erectile dysfunction after radical prostatectomy or radiotherapy for prostate cancer: a population-based cohort study. Lancet Oncology. 2014 Feb;15(2):223-231.
- Hamilton SN, Tyldesley S, Hamm J, Jiang WN, Keyes M, Pickles T, Lapointe V, Kahnamelli A, McKenzie M, Miller S, Morris WJ. Incidence of Second Malignancies in Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy and Radical Prostatectomy. Int J Radiat Oncol Biol Phys. 2014 Nov 15;90(4):934-941.
- Hinnen KA, Schaapveld M, van Vulpen M, Battermann JJ, van der Poel H, van Oort IM, van Roermund JG, Monninkhof EM. Prostate brachytherapy and second primary cancer risk: a competitive risk analysis. J Clin Oncol. 2011 Dec 1;29(34):4510-5.
Jessica Conway, MD and Michael McKenzie, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Radiation Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency