Intensity modulated radiotherapy (IMRT) for prostate cancer

PICHON RIVIERE, A.; AUGUSTOVSKI, F.; GARCIA MARTI, S.; GLUJOVSKY, D.; LOPEZ, A.; ALCARAZ, A.; BARDACH, A.; CIAPPONI, A; MEZA, V

Documento de Evaluación de tecnologías Sanitarias

IECS

Año: 2013 p. 1 - 30

1668-2793

In Argentina, prostate cancer (PC) is the second cause of death cancer in men. External radiation therapy (RT) may be used in all the disease stages. At present, the most commonly used technique is 3D-conformal radiation therapy (3D-CRT). IMRT is proposed as a therapeutic alternative that might have the potential to administer high doses with less adverse events.TechnologyIMRT is a form of 3D-CRT which through planning and a multileaf collimator allows to modulate the number and doses of radiation beams. This enables to irradiate the tumor with higher doses minimizing the radiation received by the surrounding organs.PurposeTo assess the available evidence on the efficacy, safety and coverage policy related aspects regarding the use of IMRT in patients with prostate cancer.MethodsA bibliographic search was carried out on the main databases: DARE, NHS EED, on Internet general search engines, in health technology evaluation agencies and health sponsors. Priority was given to the inclusion of systematic reviews (SR); controlled randomized clinical trials (RCTs); health technology assessments and economic evaluations, clinical practice guidelines (CPG), coverage policies of other health systems and case series reports with mortality and/or disease-free survival results.ResultsThis report includes five SRs, three non-randomized controlled studies, two case series reports, four economic evaluations, three health technology assessments, eight CPGs and information on coverage from health sponsors. All the studies found assessed patients with localized or locally advanced PC; no studies assessing this technique as adjuvant or rescue radiation therapy or in patients with bone metastases have been found.One SR from 2010 included eight studies which compared case series of IMRT with 3D-CRT; no RCT has been identified. The quality of the included studies is poor. None of the studies reported differences in terms of overall or disease-free survival in both techniques. Two studies did not find differences in biochemical relapse free survival (BRFS), while another one found a longer BRFS with IMRT (72.6,6% vs. 50.1%,p<0.01 and 60.2% vs. 35%, p=0.02 in patients with intermediate and high risk of relapse respectively). No study identified a clear benefit for any of the techniques in terms of acute gastrointestinal (GI) and genitourinary (GU) toxicity. Three studies report a lower late GI toxicity with IMRT (absolute risk reduction of approximately 8-15%); and two studies report a lower late GU toxicity with 3D-CRT (absolute risk reduction of approx. 8%). The other systematic reviews included report similar results.Two non-randomized controlled studies published in 2012 that used administrative databases to compare the rate of medical service use reported a lower requirement of new anticancer treatments after receiving IMRT versus 3D-CRT (2.5 every 100 subjects per year vs. 3.1 and 6% of risk after three years with IMRT vs. 9% with 3D-CRT). One of the studies reported a higher risk of GI or GU complications with IMRT. The other study found a lower risk in these results as well as a lower risk of hip fracture with IMRT (0.2% difference per year), but a higher risk of sexual dysfunction in patients who had received IMRT.CPGs and recommendations from international societies consider that both 3D-CRT and IMRT may be used in prostate cancer. Other agencies suggest that IMRT should be chosen in prostate cancer patients with intermediate-high risk of relapse who are going to receive high radiation doses.All the health sponsors cover 3D-CRT, considering coverage of IMRT in certain cases.In Argentina, the cost of IMRT is four times that of 3D-CRT. In developed countries, the cost of IMRT is 1.1 to 2 times higher than that of 3D-CRT.ConclusionsThe quality of the evidence found is poor since to date, no controlled randomized clinical trials have been conducted to assess the effectiveness and safety of IMRT. The evidence suggests that IMRT might be associated with a lower biochemical relapse, lower requirement of new anticancer treatments and a lower risk of late GI toxicity. However, if this difference existed, it would be little in absolute terms. In turn, IMRT might also be associated to a higher frequency of GU toxicity and sexual dysfunction. In contrast to developed countries where the difference in the cost of both techniques is very little, in Argentina, IMRT is almost four times that of 3D-CRT. Uncertainty about its benefits, in terms of cancer, and the big difference in cost, limits its massive use in our country.If used, its use might be justified in patients with high risk of relapse, whom high doses might reduce the risk of relapse. No evidence was found to support its use in case of adjuvant, rescue therapies and/or in patients with bone metastases.