RESUMO
PURPOSE: Using the primary endpoint of time to biochemical progression (TTP), Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized National Comprehensive Cancer Network patients with intermediate and high-risk prostate cancer to low-dose-rate brachytherapy boost (LDR-PB) or dose-escalated external beam boost (DE-EBRT). Randomization to the LDR-PB arm resulted in a 2-fold reduction in biochemical progression compared with the DE-EBRT group at a median follow-up of 6.5 years (P < .001). Herein, the primary endpoint and secondary survival endpoints of the ASCENDE-RT trial are updated at a 10-year median follow-up. METHODS: Patients were randomly assigned to either the LDR-PB or the DE-EBRT arm (1:1). All patients received 1 year of androgen deprivation therapy and 46 Gy in 23 fractions of pelvic RT. Patients in the DE-EBRT arm received an additional 32 Gy in 16 fractions, and those in the LDR-PB arm received an 125I implant prescribed to a minimum peripheral dose of 115 Gy. Two hundred patients were randomized to the DE-EBRT arm and 198 to the LDR-PB arm. RESULTS: The 10-year Kaplan-Meier TTP estimate was 85% ± 5% for LDR-PB compared with 67% ± 7% for DE-EBRT (log rank P < .001). Ten-year time to distant metastasis (DM) was 88% ± 5% for the LDR-PB arm and 86% ± 6% for the DE-EBRT arm (P = .56). There were 117 (29%) deaths. Ten-year overall survival (OS) estimates were 80% ± 6% for the LDR-PB arm and 75% ± 7% for the DE-EBRT arm (P = .51). There were 30 (8%) patients who died of prostate cancer: 12 (6%) in the LDR-PB arm, including 2 treatment-related deaths, and 18 (9%) in the DE-EBRT arm. CONCLUSIONS: Men randomized to the LDR-PB boost arm of the ASCENDE-RT trial continue to experience a large advantage in TTP compared with those randomized to the DE-EBRT arm. ASCENDE-RT was not powered to detect differences in its secondary survival endpoints (OS, DM, and time to prostate cancer-specific death) and none are apparent.
Assuntos
Braquiterapia , Neoplasias da Próstata , Masculino , Humanos , Antagonistas de Androgênios/uso terapêutico , Androgênios , Pelve , Estimativa de Kaplan-Meier , Braquiterapia/métodosRESUMO
PURPOSE: The aim of this study was to characterize the patterns of prostate cancer recurrence after brachytherapy (BT) using 2-(3-[1-carboxy-5-([6-18F-fluoropyridine-3-carbonyl]-amino)-pentyl]-ureido)-pentanedioic acid ([18F]DCFPyL) prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and computed tomography (CT) imaging. METHODS AND MATERIALS: Patients were selected from an ongoing prospective institutional trial investigating the use of [18F]DCFPyL PSMA PET and CT in recurrent prostate cancer (NCT02899312). This report included patients who underwent BT (either monotherapy or boost) and experienced a biochemical failure (BF) defined by the Phoenix definition (prostate-specific antigen [PSA] > 2 ng/mL above nadir). RESULTS: Between March 2017 and April 2020, 670 patients underwent [18F]DCFPyL PSMA PET and CT imaging. Of these 670 patients, 93 were treated with BT; 73 underwent monotherapy, and 20 underwent BT boost (19 low-dose rate and 1 high-dose rate). To report on patterns of recurrence outcomes, 86 patients (median prescan PSA 6.0) with a positive [18F]DCFPyL PSMA PET and CT scan and true BF were included. The most common location of relapse was local; 62.8% had a component of local failure (defined as prostate and/or seminal vesicles), and 46.5% had isolated local failure only, with no other sites of involvement. Regional failure occurred in 40.7% of patients, and 36.0% had metastatic failure. Isolated local recurrence was seen in 54.3% of monotherapy patients versus only in 12.5% of boost patients. Metastatic failure was seen in 28.6% of monotherapy patients versus 68.8% of the boost patients. Local recurrences (69.0%) were found within the same prostate biopsy sextant involved with the tumor at diagnosis, and 76.0% of patients with seminal vesicle recurrences had prostate-base involvement at diagnosis. CONCLUSIONS: Contrary to previous evidence, our study suggests that in prostate BT patients with biochemical recurrence, the most common site of failure is local for the patients treated with monotherapy and metastatic for patients treated with a combination of external beam radiation and BT boost.
Assuntos
Braquiterapia , Neoplasias da Próstata , Humanos , Lisina , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Tomografia Computadorizada por Raios X , UreiaRESUMO
PURPOSE: The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS: The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS: LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure. CONCLUSIONS: LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.
Assuntos
Braquiterapia , Neoplasias da Próstata , Antagonistas de Androgênios , Braquiterapia/métodos , Consenso , Humanos , Masculino , Estudos Prospectivos , Antígeno Prostático Específico , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Estudos RetrospectivosRESUMO
PURPOSE: To determine late urinary toxicity (>12 months) in a large cohort of uniformly treated low-dose-rate prostate brachytherapy patients. METHODS AND MATERIALS: From 1998 to 2009, 2709 patients with National Comprehensive Cancer Network-defined low-risk and low-tier intermediate-risk prostate cancer were treated with Iodine 125 ((125)I) low-dose-rate prostate brachytherapy; 2011 patients with a minimum of 25 months of follow-up were included in the study. Baseline patients, treatment, implant factors, and late urinary toxicity (Radiation Therapy Oncology Group [RTOG] grading system and International Prostate Symptom Score [IPSS]) were recorded prospectively. Time to IPSS resolution, late RTOG genitourinary toxicity was examined with Kaplan-Meier and log-rank tests. Cox proportional hazards regression was done for individual covariates and multivariable models. RESULTS: Median follow-up was 54.5 months (range, 2-13 years). Actuarial toxicity rates reached 27% and 10% (RTOG ≥2 and ≥3, respectively) at 9-13 years. Symptoms resolved quickly in the majority of patients (88% in 6-12 months). The prevalence of RTOG 0, 1, 2, 3, and 4 toxicity with a minimum of 7 years' follow-up was 70%, 21%, 6.4%, 2.3%, and 0.08%, respectively. Patients with a larger prostate volume, higher baseline IPSS, higher D90, acute toxicity, and age >70 years had more late RTOG ≥2 toxicity (all P≤.02). The IPSS resolved slower in patients with lower baseline IPSS and larger ultrasound prostate volume, those not receiving androgen deprivation therapy, and those with higher D90. The crude rate of RTOG 3 toxicity was 6%. Overall the rate of transurethral resection of the prostate was 1.9%; strictures, 2%; incontinence, 1.3%; severe symptoms, 1.8%; late catheterization, 1.3%; and hematuria, 0.8%. The majority (80%) resolved their symptoms in 6-12 months. CONCLUSION: Long-term urinary toxicity after brachytherapy is low. Although actuarial rates increase with longer follow-up (27% RTOG 2 and 10% RTOG 3 at 13 years), symptoms resolve relatively quickly; between 5 and 13 years' follow-up, >90% of patients have minimal urinary toxicity. Refining patient selection criteria, planning, and treatment delivery may further reduce toxicity.
Assuntos
Braquiterapia/efeitos adversos , Radioisótopos do Iodo/efeitos adversos , Neoplasias da Próstata/radioterapia , Lesões por Radiação/epidemiologia , Transtornos Urinários/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Braquiterapia/métodos , Colúmbia Britânica , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Fatores de Tempo , Transtornos Urinários/etiologiaRESUMO
PURPOSE: To examine the relationship between whole prostate dose metrics and disease-free survival (DFS) after (125)I low-dose-rate prostate brachytherapy (LDR-PB). METHODS AND MATERIALS: Data for the first 2000 LDR-PB monotherapy implants were extracted from a database containing patient, tumor, dosimetric, and outcomes information. By National Comprehensive Cancer Network criteria, half (n = 1006) had low-risk disease and half (n = 990) had intermediate-risk disease (four had high-risk disease). Most patients (58.4%) and 75.3% of intermediate-risk patients received 3 months neoadjuvant and 3 months concomitant androgen deprivation therapy (ADT). Univariate and multivariate analyses were conducted using recognized prognostic factors and the whole prostate dose metrics D90 (the minimum dose received by 90% of the postimplant CT-based prostate volume) and V100 (the percent of the postimplant CT-based prostate volume that received at least 100% of the prescription dose). RESULTS: The median followup is 5 years (maximum, 12.5 years); the 5-, 7-, and 10-year actuarial DFS estimates are 96.0%, 94.4%, and 93.0%, respectively. Of the recognized prognostic factors, only pretreatment prostate-specific antigen (p = 0.012) and Gleason sum (p = 0.010) were predictive of DFS. When analyzed as continuous variables, dose metrics were not predictive of DFS. However, most nonsignificant trends favored higher doses, and D90 values <130 Gy were predictive of an increased risk of recurrence in the non-ADT subset (N = 833; log rank, p = 0.018). CONCLUSIONS: Although D90 values of <130 Gy were predictive of an increased risk of recurrence in the non-ADT subset, neither D90 nor V100, when used as continuous variables, was predictive of DFS when applied to the entire cohort or in the subset analysis. This observation informs us that dose metrics are not equivalent to oncologic end points and must be calibrated against DFS for each physician and each institution offering LDR-PB.
Assuntos
Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Relação Dose-Resposta à Radiação , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Radiometria , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: The objective of this study was to report the rates of disease-free survival (DFS), cause-specific survival (CSS), and overall survival after low-dose-rate (LDR) prostate brachytherapy (PB). METHODS: Data from 1006 consecutive patients with prostate cancer who received LDR-PB and underwent implantation on or before October 23, 2003 were extracted from a prospective database on November 11, 2011. The selected patients had low-risk (58%) or intermediate-risk (42%) disease according to National Comprehensive Cancer Network criteria. The Phoenix threshold was used to define biochemical relapse. Sixty-five percent of patients received 3 months of neoadjuvant androgen-deprivation therapy (ADT) and 3 months of concomitant ADT. Univariate and multivariate analyses are reported in relation to patient, tumor, and treatment variables. RESULTS: The median follow-up was 7.5 years. By using Fine and Gray competing risks analysis, the 5-year and 10-year actuarial DFS rates were 96.7% (95% confidence interval, 95.2%-97.7%) and 94.1% (95% confidence interval, 92%-95.6%), respectively. When applied to the whole cohort, none of the usual prognostic variables, including dose metrics, were correlated with DFS. However, in both univariate and multivariate models, increasing dose was the only covariate that correlated with improved DFS for the subset of men (N = 348) who did not receive ADT (P = .043). The actuarial 10-year CSS rate was 99.1% (95% confidence interval, 97.3%-99.7%). The overall survival rate was 93.8% at 5 years (95% confidence interval, 92%-95.1%) and 83.5% at 10 years (95% confidence interval, 79.8%-86.6%). Only age at implantation (P = .0001) was correlated with overall survival in multivariate analysis. CONCLUSIONS: In a consecutive cohort of 1006 men with National Comprehensive Cancer Network low-risk and intermediate-risk prostate cancer, the actuarial rate of recurrent disease after LDR-PB was approximately 3% at 5 years and 6% at 10 years.
Assuntos
Braquiterapia/métodos , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Dosagem Radioterapêutica , Análise de SobrevidaRESUMO
BACKGROUND AND PURPOSE: To evaluate outcome in patients with Gleason 7 prostate cancer treated with iodine-125 brachytherapy at the British Columbia Cancer Agency. MATERIALS AND METHODS: Between 20th July 1998 and 7th February 2006, 1500 patients underwent I-125 prostate brachytherapy without supplemental external beam radiation therapy. Of these, 439 had Gleason 7 disease; 362 had Gleason 3+4 and 77 had 4+3 disease. Generally, patients received 6 months of androgen suppression. We compared biochemical no evidence of disease (bNED) between patients with Gleason ≤ 6 and Gleason 7 and between Gleason 3+4 and 4+3 using the Phoenix definition of biochemical recurrence. RESULTS: Median follow-up was 60 months. Estimated 5 year bNED was 97% for patients with Gleason score ≤ 6 and 94% for patients with Gleason 7 disease (p=0.037). Estimated bNED was 95% and 94% for 3+4 and 4+3, respectively (p=0.791). There was no difference in bNED between implants achieving D90 ≥ versusAssuntos
Braquiterapia
, Radioisótopos do Iodo/uso terapêutico
, Neoplasias da Próstata/radioterapia
, Idoso
, Idoso de 80 Anos ou mais
, Estudos de Coortes
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Gradação de Tumores
, Neoplasias da Próstata/patologia
, Dosagem Radioterapêutica
, Resultado do Tratamento
RESUMO
BACKGROUND AND PURPOSE: To describe the incidence of urinary incontinence among prostate cancer patients treated with external beam radiotherapy (RT) and to investigate associated risk factors. PATIENTS AND METHODS: One thousand and hundred ninety-two patients with >or=24 months follow-up were the subjects of this series. All patients received between 50 and 72 Gy in 20-37 fractions (median 66 Gy/33#). Post-RT urinary incontinence was scored by direct patient interviewing according to the modified RTOG/SOMA scale: Grade 1--occasional use of incontinence pads, Grade 2--intermittent use of incontinence pads, Grade 3--persistent use of incontinence pads, and Grade 4--permanent catheter. Risk-factors investigated were: age, diabetes, TURP prior to RT, elapsed time from TURP to RT, clinical stage, RT dose and presence of Grade >or=2 acute GU and GI toxicity. Non-parametric, actuarial univariated (Kaplan-Meier) and multivariated tests (MVA, Cox regression) were performed. RESULTS: Median follow-up for the group is 52 months (24-109). Thirty-four patients (2.9%) had incontinence prior to RT, which was more common in TURP patients (7.8% vs 1.6% P<0.001). These are excluded from further analysis. Fifty-seven patients (4.9%) developed Grade 1 incontinence, 7 (0.6%) Grade 2, and 7 (0.6%) Grade 3. There was no Grade 4 incontinence. Actuarial rates for Grade >or=1 and >or=2 incontinence at 5 years are 7 and 1.7%, respectively. Risk factors on MVA associated with the development of Grade 1 or worse incontinence are pre-RT TURP (5-year rates 10% vs 6%, P=0.026), presence of Grade >or=2 acute GU toxicity (5-year rates 11% vs 5%, P=0.002). Age, diabetes, clinical stage, elapsed time from TURP to RT, RT dose or fraction size, acute GI toxicity were not significant. Patients who underwent post-RT TURP or dilatation for obstructive symptoms (4.3%), were more likely to develop Grade 2-3 incontinence (5-year rate 8 vs 1.5%, P=0.0015). CONCLUSIONS: Grade 2 or greater urinary incontinence is rare among patients who have been treated with external beam radiotherapy. Associated risk factors are pre-RT TURP and the presence of increased acute GU toxicity. Post-radiaton TURP increases the risk of incontinence five-fold.