Intensity modulated radiotherapy (IMRT) or conformational radiotherapy (3D-CRT) with conventional fractionation for prostate cancer: Is there any clinical difference?

ABSTRACT Purpose: To compare the treatment outcomes of a cohort of prostate cancer patients treated with conventional schedule using IMRT or 3DRT technique. Materials and Methods: Between 2010-2017, 485 men with localized prostate cancer were treated with conventional radiotherapy schedule with a total dose ≥74Gy using IMRT (231) or 3DCRT (254). Late gastrointestinal (GI) and genitourinary (GU) toxicity were retrospectively evaluated according to modified RTOG criteria. The biochemical control was defined by the Phoenix criteria (nadir + 2ng/mL). The comparison between the groups included biochemical recurrence free survival (bRFS), overall survival (OS) and late toxicity. Results: With a median follow-up of 51 months (IMRT=49 and 3DRT=51 months), the maximal late GU for >=grade- 2 during the entire period of follow-up was 13.1% in the IMRT and 15.4% in the 3DRT (p=0.85). The maximal late GI ≥ grade- 2 in the IMRT was 10% and in the 3DRT 24% (p=0.0001). The 5-year bRFS for all risk groups with IMRT and 3D-CRT was 87.5% vs. 87.2% (p=0.415). Considering the risk-groups no significant difference for low-, intermediate- and high-risk groups between IMRT (low-95.3%, intermediate-86.2% and high-73%) and 3D-CRT (low-96.4%, intermediate-88.2% and high-76.6%, p=0.448) was observed. No significant differences for OS and DMFS were observed comparing treatment groups. Conclusion: IMRT reduces significantly the risk of late GI severe complication compared with 3D-CRT using conventional fractionation with a total dose ≥74Gy without any differences for bRFS and OS.

Análise de custo-efetividade da técnica de IMRT para o tratamento do câncer de próstata localizado / Cost-effectiveness analysis of the IMRT technique for the treatment of localized prostate cancer

De acordo com os dados do Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA), foram esperados, no Brasil, 61.200 novos casos de câncer de próstata para o ano de 2016. Estabelecido o diagnóstico, as opções terapêuticas são consideradas e se baseiam no estadiamento, dosagem do antígeno prostático específico (PSA) e escore histológico de Gleason. Segundo as diretrizes diagnósticas e terapêuticas do adenocarcinoma de próstata publicadas (2015), a técnica de radioterapia de intensidade modulada (IMRT) apresenta benefício no controle da doença e a menor probabilidade de toxicidade. Este trabalho teve como objetivo analisar a custo-efetividade da técnica de IMRT, na perspectiva do SUS, para o tratamento do câncer de próstata localizado, comparada com a técnica conformacional (3DRT). Foi construído um modelo de Markov e, uma coorte hipotética de homens de 65 a 70 anos foi acompanhada por 10 anos. A medida de desfecho clínico foram os anos de vida ajustados para qualidade (QALY). Os custos levantados se basearam nos valores da tabela APAC para um tratamento na dose de 74 a 76 Gy. Análise de sensibilidade probabilística baseada em simulação de Monte Carlo a fim de construir um limiar de aceitabilidade para incorporação da tecnologia em questão foi desenvolvida. O uso da tecnologia IMRT proporcionou um incremento de 0,79 QALY, mas não se mostrou custo-efetiva em relação aos pacientes que receberam radioterapia pela 3DRT. A IMRT apresentou uma razão de custoefetividade incremental de R$10.580,98/QALY. Ao considerar um limiar de aceitabilidade de três vezes o produto interno bruto (PIB) per capita, segundo recomendação da Organização Mundial de Saúde (2011), estimado em R$ 86.628,00/QALY, para 2016, o cenario para a incorporaçao dessa tecnologia se apresenta favoravel. A probabilidade do IMRT ser custo-efetiva foi de 72,5% para limiares de aceitabilidade de R$15.000,00

According to data from the Coordination of Prevention and Surveillance of the National Cancer Institute José Alencar Gomes da Silva (NCI) 61,200 new cases of prostate cancer were expected in Brazil in 2016. Once the diagnosis is established, the therapeutic options are considered according to risk groups described by D'Amico (1998), which are based on staging, prostate-specific antigen (PSA) and Gleason score. For localized prostate tumors, and for all risk groups, radiotherapy is indicated. According to the diagnostic and therapeutic guideline of prostate adenocarcinoma published in October 2015, the intensity modulated radiotherapy (IMRT) technique has a benefit in controlling the disease and the lower probability of toxicity. According to this premise, this study aimed to analyze the costeffectiveness of the IMRT technique, from the perspective of SUS, for the treatment of localized prostate cancer, compared with three-dimensional technique (3DRT). A mathematical model based on Markov models was constructed and a hypothetical cohort of men aged 65 to 70 years was followed up for 10 years. A probabilistic sensitivity analysis was performed based on Monte Carlo simulation to construct a threshold of acceptability for incorporation of the technology in question. As a result of the study, the use of IMRT technology provided a 0.79-year increase in quality-adjusted life years (QALY), but was not cost-effective compared to patients who received radiotherapy using the 3DRT. The IMRT presented an incremental cost-effectiveness ratio of R $ 10,580.98 / QALY. Based on a threshold of three times the per capita GDP, according to the WHO recommendation (2011), calculated at R $ 86,628.00 / QALY for 2016, the scenario for the incorporation of this technology is favorable. If a threshold of acceptability of R $ 28,876 is considered equivalent to a GDP per capita, the probability of IMRT being cost-effective is 72%

External beam radiation therapy and a low-dose-rate brachytherapy boost without or with androgen deprivation therapy for prostate cancer

Purpose To assess outcomes with external beam radiation therapy (EBRT) and a low-dose-rate (LDR) brachytherapy boost without or with androgen deprivation therapy (ADT) for prostate cancer. Materials and Methods From January 2001 through August 2011, 120 intermediate-risk or high-risk prostate cancer patients were treated with EBRT to a total dose of 4,500 cGy in 25 daily fractions and a palladium-103 LDR brachytherapy boost of 10,000 cGy (n = 90) or an iodine-125 LDR brachytherapy boost of 11,000 cGy (n = 30). ADT, consisting of a gonadotropin-releasing hormone agonist ± an anti-androgen, was administered to 29/92 (32%) intermediate-risk patients for a median duration of 4 months and 26/28 (93%) high-risk patients for a median duration of 28 months. Results Median follow-up was 5.2 years (range, 1.1-12.8 years). There was no statistically-significant difference in biochemical disease-free survival (bDFS), distant metastasis-free survival (DMFS), or overall survival (OS) without or with ADT. Also, there was no statistically-significant difference in bDFS, DMFS, or OS with a palladium-103 vs. an iodine-125 LDR brachytherapy boost. Conclusions There was no statistically-significant difference in outcomes with the addition of ADT, though the power of the current study was limited. The Radiation Therapy Oncology Group 0815 and 0924 phase III trials, which have accrual targets of more than 1,500 men, will help to clarify the role ADT in locally-advanced prostate cancer patients treated with EBRT and a brachytherapy boost. Palladium-103 and iodine-125 provide similar bDFS, DMFS, and OS. .

Early stage prostate cancer: biochemical recurrence after treatment

Objectives To identify retrospectively through chart analysis the biochemical recurrence frequency of localized prostate cancer at diagnosis of patients submitted to surgery or radiotherapy; to correlate diagnostic characteristics associated with higher risk of biochemical recurrence.Materials and Methods Retrospective analysis of 483 patients treated in a single center, from March 2000 to December 2009 in order to verify factors associated with biochemical recurrence.Results Biochemical recurrence was more frequent in patients with higher initial PSA levels and those with higher risk disease. Recurrence was more frequent in patients with high risk (25.9%) than those with intermediate risk (10.7%) and low risk (5.5%). There was no significant statistical difference of biochemical recurrence between patients submitted to radiotherapy or radical prostatectomy. Biochemical recurrence was diagnosed in only 11 of 73 patients (15%) submitted to conformal radiotherapy using tridimensional technique.Conclusion Radiotherapy and radical prostatectomy have similar treatment results. Tridimensional conformal radiotherapy used nowadays is more efficient than earlier forms of radiation therapy (cobalt therapy and bidimensional linear accelerator therapy).

Evaluation of Acute Toxicity and Symptoms Palliation in a Hypofractionated Weekly Schedule of External Radiotherapy for Elderly Patients with Muscular Invasive Bladder Cancer

Aim To evaluate acute toxicity and symptoms palliation of a weekly hypofractionated 3DCRT schedule as radical treatment in elderly patients with organ confined bladder cancer cT1-2N0. Materials and Methods Between February 2005 and June 2011, 58 prospectively selected patients diagnosed with organ confined bladder cancer were treated with external 3DCRT (4-field arrangement). All candidates were medically inoperable, with poor performance status, and with age ranged from 75 to 88 years (median 78). A dose of 36 Gy in 6 weekly fractions was prescribed. The primary study endpoints were the evaluation of haematuria, dysuria, frequency and pain palliation as well as the acute toxicity according to the RTOG/EORTC scale: an assessment was performed at baseline, during and 3 months after radiotherapy, while the maximum reported score was taken into account. Results The gastrointestinal acute toxicities were 13/58 (22.4%) and 5/58 (5.6%), for grade I and II respectively. The genitourinary acute toxicities were 19/58 (32.7%) and 10/58 (17.2%), for grade I and II respectively. In terms of clinical outcome, 55/58 patients (94.8%) reported palliation of haematuria, while 19 out of 58 reported no change in frequency and dysuria. All patients reported significant improvement (P < 0.01) for pain, concerning the visual analogue score before and after radiotherapy. The median progression free survival was 14 months. CONCLUSIONS The incidence of patient-reported acute toxicity following weekly hypofractionated external 3DCRT is low while the symptom palliation compares very favorably with other reported outcomes. .

Updated results of high-dose rate brachytherapy and external beam radiotherapy for locally and locally advanced prostate cancer using the RTOG-ASTRO phoenix definition

PURPOSE: To evaluate the prognostic factors for patients with local or locally advanced prostate cancer treated with external beam radiotherapy (RT) and high dose rate brachytherapy (HDR) according to the RTOG-ASTRO Phoenix Consensus Conference. MATERIALS AND METHODS: The charts of 209 patients treated between 1997 and 2005 with localized RT and HDR as a boost at the Department of Radiation Oncology, AC Camargo Hospital, Sao Paulo, Brazil were reviewed. Clinical and treatment parameters i.e.: patient's age, Gleason score, clinical stage, initial PSA (iPSA), risk group (RG) for biochemical failure, doses of RT and HDR were evaluated. Median age and median follow-up time were 68 and 5.3 years, respectively. Median RT and HDR doses were 45 Gy and 20 Gy. RESULTS: Disease specific survival (DSS) at 3.3 year was 94.2 percent. Regarding RG, for the LR (low risk), IR (intermediate risk) and HR (high risk), the DSS rates at 3.3 years were 91.5 percent, 90.2 percent and 88.5 percent, respectively. On univariate analysis prognostic factors related to DSS were RG (p = 0.040), Gleason score ¡Ü 6 ng/mL (p = 0.002), total dose of HDR ¡Ý 20 Gy (p < 0.001) On multivariate analysis the only statistical significant predictive factor for biochemical control (bNED) was the RG, p < 0.001 (CI - 1.147-3.561). CONCLUSIONS: Although the radiation dose administered to the prostate is an important factor related to bNED, this could not be established with statistical significance in this group of patients. To date , in our own experience, HDR associated to RT could be considered a successful approach in the treatment of prostate cancer.