Higher Late Genitourinary Toxicity Research Articles

Late toxicity and quality of life with prostate only or whole pelvic radiation therapy in high risk prostate cancer (POP-RT): A randomised trial

AimTo report toxicity and quality of life (QOL) outcomes from a randomised trial of prostate only versus whole pelvic radiotherapy in high risk, node negative prostate cancer. Materials/methodsPatients with localised prostate adenocarcinoma and nodal involvement risk > 20%, were randomised to prostate only (PORT, 68 Gy/25# to prostate) and whole pelvis (WPRT, 68 Gy/25# to prostate and 50 Gy/25# to pelvis) arms with stratification for TURP, Gleason score, baseline PSA, and type of androgen deprivation therapy (ADT). Image guided intensity modulated radiotherapy (IG-IMRT) and two years of ADT were mandatory. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were graded using RTOG grading. QOL was assessed using EORTC QLQ-C30 and PR-25 questionnaire pre-treatment and every 3–6 months post RT. ResultsTotal 224 patients were randomised (PORT 114, WPRT 110) from November 2011 to August 2017. Median follow up was 44.5 months. No RTOG grade IV toxicity was observed. Acute GI and GU toxicities were similar between both the arms. Cumulative ≥ grade II late GI toxicity was similar for WPRT and PORT (6.5% vs. 3.8%, p = 0.39) but GU toxicity was higher (17.7% vs. 7.5%, p = 0.03). Dosimetric analysis showed higher bladder volume receiving 30–40 Gy in the WPRT arm (V30, 60% vs. 36%, p < 0.001; V40, 41% vs. 25%, p < 0.001). There was no difference in QOL scores of any domain between both arms. ConclusionPelvic irradiation using hypofractionated IG-IMRT resulted in increased grade II or higher late genitourinary toxicity as compared to prostate only RT, but the difference was not reflected in patient reported QOL. Clinicaltrials.gov NCT02302105Prostate Only or Whole Pelvic Radiation Therapy in High Risk Prostate Cancer (POP-RT).

Late toxicity for prostate cancer patients treated with hypofractionated helical tomotherapy.

The purpose of this study is to evaluate the long term tolerability of hypofractionated helical tomotherapy (HT) in localized prostate cancer patients. Previous hypofractionated schedules with conventional RT were associated with excessive toxicity, likely due to inadequate sophistication of treatment delivery. There are few data about late toxicity after HT. We evaluated 38 patients with primary adenocarcinoma of the prostate. There were 9 (24%), 15 (39%), and 14 (37%) patients with high, intermediate, and low risk, respectively. Patients were treated with hypofractionated HT from May 2008 to February 2011. Hypofractionation regimens included: 68.04Gy at 2.52Gy/fraction (N=25; 66%), 70Gy at 2.5Gy/fraction (N=4; 11%) and 70.2Gy at 2.6Gy/fraction (N=9; 23%). Late genitourinary (GU) and gastrointestinal (GI) toxicity was scored using the Radiation Therapy Oncology Group scoring system. Median age at diagnosis was 70 years (range 49-80) and median follow-up, 5.8 years. Late grade 1, 2 and 3 GI toxicity were 13%, 24%, and 2.6%, respectively. Late grade 1, 2, 3 GU toxicity were 29%, 21%, and 8%, respectively. Sexual toxicity was evaluated in 19 patients to be grade 1, 2 in 11% and grade 3 in 16%. Multivariate analysis showed that patients with higher values of rectum V50 associated with late GI toxicity (P=0.025). Patients with PSA ≤8 (P=0.048) or comorbidities (P=0.013) at diagnosis were associated with higher late GU toxicity. Additionally, PSA ≤8 also associated with moderate (grade ≥2) late GU toxicity in the multivariate analysis (P=0.028). Hypofractionated HT can be delivered safely with limited rates of moderate and severe late toxicity. The proportion of the rectum that receives a moderate and high dose, having comorbidities, and PSA at diagnosis seem to associate with long term toxicity.

Outcomes for prostate glands >60 cc treated with low-dose-rate brachytherapy

PurposeWe sought to analyze whether outcomes of biochemical relapse–free survival (bRFS), late genitourinary (GU), and late gastrointestinal toxicity are different for prostate cancer patients with small (≤60 cc) vs. large (>60 cc) prostates following low dose-rate brachytherapy. Methods and MaterialsThe bRFS outcomes for 2076 low- or intermediate-risk prostate cancer patients from 1996 to 2012 were determined from a review of a prospectively maintained database. All patients were treated with 125I monotherapy without androgen deprivation therapy. Biochemical failure was defined per the Phoenix definition. Patient-related factors and dosimetric values were examined in Cox regression analyses for bRFS and late toxicity. Late toxicity was scored according to a modified Common Terminology Criteria for Adverse Events version 4.0 scale. ResultsThe median followup for all patients was 55 months. The 5-year bRFS rates for all patients, prostates >60 cc, and prostates ≤60 cc were 93.4% (95% confidence interval [CI]: 92.1%, 94.7%), 96.7% (95% CI: 94.4%, 98.9%), and 92.9% (95% CI: 91.4%, 94.3%), respectively. On multivariable analysis, prostate size >60 cc was significantly associated with improved bRFS (p = 0.01), as were initial prostate-specific antigen and biopsy Gleason score (p < 0.0001 and p = 0.0002, respectively). Patients with prostates >60 cc had significantly higher rates of Grade 3–4 late GU toxicity at 5 years than patients with smaller prostates; 7.2% (95% CI: 4.0%, 10.4%) and 3.2% (95% CI: 2.3%, 4.1%), respectively (p = 0.0007). The overall late gastrointestinal toxicity rate for all patients was 0.7% at 5 years with no significant difference between the two groups. ConclusionsImplantation of large prostates >60 cc results in favorable bRFS outcomes and is associated with increased but acceptable rates of Grade 3 and higher late GU toxicities.

Commentary on Prospective assessment of gastrointestinal and genitourinary toxicity of salvage radiotherapy for patients with prostate-specific antigen relapse or local recurrence after radical prostatectomy: Pearse M, Choo R, Danjoux C, Gardner S, Morton G, Szumacher E, Loblaw A, Cheung P, Department of Radiation Oncology, Auckland Hospital, Auckland, New Zealand

To assess the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity of salvage radiotherapy (RT). A total of 75 patients with prostate-specific antigen relapse or clinically isolated local recurrence after radical prostatectomy were accrued between 1998 and 2002 for a Phase II study to evaluate the efficacy of salvage RT plus 2-year androgen suppression. Acute and late GI and GU toxicity were prospectively assessed using the National Cancer Institute Expanded Common Toxicity Criteria version 2. For acute toxicity, prevalence was examined. For late toxicity, cumulative incidences of Grade 2 or higher and Grade 3 toxicity were calculated. Median age was 67 years at the time of salvage RT. Median time from radical prostatectomy to RT was 36.2 months. Median follow-up was 45.1 months. Seventy-five patients were available for acute toxicity analysis, and 72 for late toxicity. Twelve percent and 40% had pre-existing GI and GU dysfunction before RT, respectively. Sixty-eight percent, 21%, and 5% experienced Grades 1, 2, and 3 acute GI or GU toxicity, respectively. Cumulative incidences of Grade 2 or higher late GI and GU toxicity at 36 months were 8.7% and 22.6%, and Grade 3 late GI and GU toxicity, 1.6% and 2.8%, respectively. None had Grade 4 late toxicity. The severity of acute GU toxicity (Grade < 2 vs. >/= 2) was a significant predictor factor for Grade 2 or higher late GU toxicity after adjusting for pre-existing GU dysfunction. Salvage RT generally was well tolerated. Grade 3 or higher late GI or GU toxicity was uncommon.

Prospective Assessment of Gastrointestinal and Genitourinary Toxicity of Salvage Radiotherapy for Patients With Prostate-Specific Antigen Relapse or Local Recurrence After Radical Prostatectomy

To assess the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity of salvage radiotherapy (RT). A total of 75 patients with prostate-specific antigen relapse or clinically isolated local recurrence after radical prostatectomy were accrued between 1998 and 2002 for a Phase II study to evaluate the efficacy of salvage RT plus 2-year androgen suppression. Acute and late GI and GU toxicity was prospectively assessed using the National Cancer Institute Expanded Common Toxicity Criteria Version 2. For acute toxicity, prevalence was examined. For late toxicity, cumulative incidences of Grade 2 or higher and Grade 3 toxicity were calculated. Median age was 67 years at the time of salvage RT. Median time from radical prostatectomy to RT was 36.2 months. Median follow-up was 45.1 months. Seventy-five patients were available for acute toxicity analysis, and 72 for late toxicity. Twelve percent and 40% had preexisting GI and GU dysfunction before RT, respectively. Sixty-eight percent, 21%, and 5% experienced Grade 1, 2, and 3 acute GI or GU toxicity, respectively. Cumulative incidences of Grade 2 or higher late GI and GU toxicity at 36 months were 8.7% and 22.6%, and Grade 3 late GI and GU toxicity, 1.6% and 2.8%, respectively. None had Grade 4 late toxicity. The severity of acute GU toxicity (Grade < 2 vs. >/= 2) was a significant predictor factor for Grade 2 or higher late GU toxicity after adjusting for preexisting GU dysfunction. Salvage RT generally was well tolerated. Grade 3 or higher late GI or GU toxicity was uncommon.

Predictive Factors for Late Genitourinary and Gastrointestinal Toxicity in Patients With Prostate Cancer Treated With Adjuvant or Salvage Radiotherapy

To determine the rate and magnitude of late genitourinary (GU) and gastrointestinal (GI) toxicities after salvage or adjuvant radiotherapy (RT) for prostate cancer, and to determine predictive factors for these toxicities. A large multi-institutional database that included 959 men who received postoperative RT after radical prostatectomy (RP) was analyzed: 19% received adjuvant RT, 81% received salvage RT, 78% were treated to the prostate bed only, and 22% received radiation to the pelvis. The median follow-up time was 55 months. At 5 years, 10% of patients had Grade 2 late GU toxicity and 1% had Grade 3 late GU toxicity, while 4% of patients had Grade 2 late GI toxicity and 0.4% had Grade 3 late GI toxicity. Multivariate analysis demonstrated that adjuvant RT (p = 0.03), androgen deprivation (p < 0.0001), and prostate bed-only RT (p = 0.007) predicted for Grade 2 or higher late GU toxicity. For GI toxicity, although adjuvant RT was significant in the univariate analysis, no significant factors were found in the multivariate analysis. Overall, the number of high-grade toxicities for postoperative RT was low. Therefore, adjuvant and salvage RT can safely be used in the appropriate settings.

Acute and late genitourinary toxicity of conformal radiotherapy for prostate cancer

The aim of this study was to identify predictive factors for genitourinary (GU) toxicity in prostate cancer patients who underwent conformal radiotherapy (CRT). In this study we analyzed 154 cases of T1-3N0M0 prostate adenocarcinoma and evaluated the occurrence rate of acute and late GU toxicity and the duration of acute toxicity according to clinical parameters: age, transurethral resection of the prostate prior to CRT, hormone therapy, CRT dose, length of planning target volume (PTV). Altogether, 41% of the patients developed grade 2 or higher acute GU toxicity. Longer PTV was significantly associated with a higher incidence of acute GU toxicity (>7 cm, 53%; <or=7 cm, 31%; P = 0.003), and hormone therapy prolonged the duration of the toxicity (P = 0.007). Grade 1 or higher late GU toxicity developed in 23% of the patients, and the 2-year late GU toxicity-free survival rate was 79%. Acute GU toxicity was significantly associated with the late GU toxicity-free survival rate (grade 0-1, 88.7%; grade 2-4, 73.2%; P = 0.0007). The length of PTV and hormone therapy were predictive factors for acute GU toxicity. Furthermore, acute GU toxicity was the most important predictive factor for late GU toxicity.

Predictive Factors for Late Genitourinary and Gastrointestinal Toxicity in Patients with Prostate Cancer Treated with Adjuvant or Salvage Radiotherapy

Purpose/Objective: Radiotherapy (RT) is frequently used following radical prostatectomy (RP) in the adjuvant (ART) or salvage (SRT) setting. The use of ART has been somewhat limited due to concerns regarding cumulative toxicity. However, with mounting evidence suggesting that ART may lead to improved outcome for specific operative findings, use of ART may increase. More information is needed to better characterize toxicity. A large multi-institutional database with men who received ART or SRT after RP was analyzed for the magnitude of toxicity and predictors of late genitourinary (GU) and gastrointestinal (GI) toxicity. Materials/Methods: The characteristics of 959 men with a median follow up of 55 mo were analyzed. Pathologic stage was T1 in 6%, T2 in 30%, T3-4 in 64%. Gleason score was 2–6 in 29%, 7 in 49%, and 8–10 in 22%. 26% had seminal vesicle involvement and 60% had positive surgical margins. 15% received androgen deprivation (AD) for a median of 6 mo (range 1–80). 19% received ART, as defined by RT within 1 year of RP and PSA<0.2 ng/ml, with a median time from RP to RT of 4 mo (range 2–12). 81% received SRT, with a median time from RP to RT of 20 mo (range 2–155). 78% were treated to the prostate bed only (P), while 22% received radiation to the pelvis (WP). Dose ranged from 50–78 Gy, with a median of 64 Gy. GI and GU toxicity were graded using standard RTOG criteria. Stepwise Cox multivariate models for grade 2 or higher GU and GI toxicity were constructed with covariates including type of RT (SRT vs. ART), use of AD, RT dose and RT target (P vs. WP). Results: 12% of patients (13% P, 7%WP) had grade 2 or higher GU toxicity. 4% of patients (5% P, 2% WP) had grade 2 or higher GI toxicity. The distribution for all patients with grade 2 or higher GU toxicity was grade 2 in 86%, grade 3 in 12%, and grade 4 in 1%. For GI toxicity, the distribution was 84%, 9%, and 7%, respectively. In P patients, median dose was 64.8 Gy (range 54–78). In WP patients, median dose was 62 Gy (range 50–70.3). This difference was significant (p<0.0001) using the non-parametric Wilcoxon statistic. Both univariate and multivariate analysis demonstrated that ART (p=0.03), AD (p=0.0003), and prostate RT (p=0.004) significantly predicted for grade 2 or higher late GU toxicity, with hazard ratios of 1.58, 2.27, and 2.19, respectively. For GI toxicity, although ART and dose were significant in univariate analysis, there were no significant factors found in multivariate analysis. Conclusions: Overall, the number of high grade toxicities for postoperative RT is low. ART, AD, and P RT predicted for grade 2 or higher late GU toxicity. There were no predictors for GI toxicity found in this analysis. This suggests that radiotherapy before maximal recovery of urinary function, which can take up to 2 years, may be associated with more GU morbidity. The finding of increased GU toxicity with P RT was unexpected and suggests that other patient or treatment technique factors influencing toxicity have not yet been characterized.