To determine the incidence of second primary cancers (SPCs) and radiotherapy-induced SPCs (RTSPCs).
The incidence of SPCs and RTSPCs was compared among four treatment groups with locoregional prostate adenocarcinoma in the 1973-2002 Surveillance, Epidemiology, and End Results database. These groups were no radiotherapy (RT), no surgery (Group 1); external beam RT (EBRT) (Group 2); brachytherapy (Group 3); and a combination of EBRT and brachytherapy (Group 4).
The age-adjusted estimates of SPCs were greater with EBRT than with brachytherapy (2,178 vs. 1,901 SPCs/100,000; p = 0.025) or with the no RT, no surgery group (1,971 SPCs/100,000; p <0.0001). The age-adjusted rate of late SPC (>or=5 years) for EBRT (2,425 SPCs/100,000) was only significantly greater (p <0.0001) than that for no RT, no surgery (1,950 SPCs/100,000). The hazard ratio adjusted for age, race/ethnicity, and grade was constant at 1.263 for EBRT compared with no RT, no surgery (p <0.0001) but varied with the length of follow-up in both the brachytherapy (0.721 at 5 years to 1.200 at 9 years) and combination (0.920 at 5 years to 1.317 at 9 years) groups. The incidence of RTSPCs was only significantly different between the no RT, no surgery group and the EBRT group, with an increase of 162 cases/100,000 or a 0.16% increased SPC risk (p = 0.023). No significant differences in the incidence of RTSPC were seen between the RT groups.
No significant differences were seen in the incidence of RTSPCs between the RT groups. The initial smaller relative risk of overall SPCs in the brachytherapy group increased with time until the curves converged, suggesting that the effect had resulted from patient selection bias.
"Study Type of data Period examined No. patients Median follow-up (years) Exclusions Time period(s) assessed Risk of second cancer at any site (based on p < 0.05 or confidence interval not including 1.0) Magnitude of risk (relative risk or other where stated (95% CI or p value if available)) Pawlish (1997)  Retrospective, SEER registry 1973– 1982 2087 RT 6.1 (mean) <1 year >1 year Increased 1.23 (1.06–1.42) 6390 no RT Brenner (2000)  Retrospective, SEER registry 1973– 1993 51,584 RT 4 (mean) <2 months Percentage increase in risk: 70,539 no RT >2 months No difference 4 (À1 to 9, p = 0.08) >5 years Increased 11 (3–20, p = 0.007) >10 years Increased 27 (9–48, p = 0.002) Abdel-Wahab (2008)  "
[Show abstract][Hide abstract] ABSTRACT: The development of a radiation induced second primary cancer (SPC) is one the most serious long term consequences of successful cancer treatment. This review aims to evaluate SPC in prostate cancer (PCa) patients treated with radiotherapy, and assess whether radiation technique influences SPC. A systematic review of the literature was performed to identify studies examining SPC in irradiated PCa patients. This identified 19 registry publications, 21 institutional series and 7 other studies. There is marked heterogeneity in published studies. An increased risk of radiation-induced SPC has been identified in several studies, particularly those with longer durations of follow-up. The risk of radiation-induced SPC appears small, in the range of 1 in 220 to 1 in 290 over all durations of follow-up, and may increase to 1 in 70 for patients followed up for more than 10 years, based on studies which include patients treated with older radiation techniques (i.e. non-conformal, large field). To date there are insufficient clinical data to draw firm conclusions about the impact of more modern techniques such as IMRT and brachytherapy on SPC risk, although limited evidence is encouraging. In conclusion, despite heterogeneity between studies, an increased risk of SPC following radiation for PCa has been identified in several studies, and this risk appears to increase over time. This must be borne in mind when considering which patients to irradiate and which techniques to employ.
Radiotherapy and Oncology 02/2014; 110(2). DOI:10.1016/j.radonc.2013.12.012 · 4.36 Impact Factor
"Some clinical data suggests that irradiated PCa patients may be at increased risk of RISPC, although the majority of clinical evidence concerns older EBRT techniques [3-12]. In terms of newer techniques, such as IMRT, BT and protons, clinical studies examining second primary cancers often have relatively low patient numbers and/or short durations of follow up [7,11,13-21]. Until further clinical information is available, planning studies provide theoretical RISPC risk estimates. "
[Show abstract][Hide abstract] ABSTRACT: A review of planning studies was undertaken to evaluate estimated risks of radiation induced second primary cancers (RISPC) associated with different prostate radiotherapy techniques for localised prostate cancer. A total of 83 publications were identified which employed a variety of methods to estimate RISPC risk. Of these, the 16 planning studies which specifically addressed absolute or relative second cancer risk using dose--response models were selected for inclusion within this review. There are uncertainties and limitations related to all the different methods for estimating SPC risk. Whether or not dose models include the effects of the primary radiation beam, as well as out-of-field regions, influences estimated risks. Regarding the impact of IMRT compared to 3D-CRT, at equivalent energies, several studies suggest an increase in risk related to increased leakage contributing to out-of-field RISPC risk, although in absolute terms this increase in risk may be very small. IMRT also results in increased low dose normal tissue irradiation, but the extent to which this has been estimated to contribute to RISPC risk is variable, and may also be very small. IMRT is often delivered using 6MV photons while conventional radiotherapy often requires higher energies to achieve adequate tissue penetration, and so comparisons between IMRT and older techniques should not be restricted to equivalent energies. Proton and brachytherapy planning studies suggest very low RISPC risks associated with these techniques. Until there is sufficient clinical evidence regarding RISPC risks associated with modern irradiation techniques, the data produced from planning studies is relevant when considering which patients to irradiate, and which technique to employ.
"The risk of a secondary cancer following the primary treatment of localised PCa should be finally addressed. Several studies showed a small but significant increase in secondary cancer, especially rectal and vesical, following irradiation, although no significant differences emerged between patients treated with EBRT or brachytherapy  "
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