A brief review of low-dose rate (LDR) and high-dose rate (HDR) brachytherapy boost for high-risk prostate

For patients with unfavorable or high-risk prostate cancer, dose escalated radiation therapy leads to improved progression free survival but attempts to deliver increased dose by external beam radiation therapy (EBRT) alone can be limited by late toxicities to nearby genitourinary and gastrointestinal organs at risk. Brachytherapy is a method to deliver dose escalation in conjunction with EBRT with a potentially improved late toxicity profile and improved prostate cancer related outcomes. At least three randomized controlled trials have demonstrated improved biochemical control with the addition of either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy to EBRT, although only ASCENDE-RT compared brachytherapy to dose-escalated EBRT but did report an over 50% improvement in biochemical failure with a LDR boost. Multiple single institution and comparative research series also support the use of a brachytherapy boost in the DE-EBRT era and demonstrate excellent prostate cancer specific outcomes. Despite improved oncologic outcomes with a brachytherapy boost in the high-risk setting, the utilization of both LDR, and HDR brachytherapy use is declining. The acute genitourinary toxicities when brachytherapy boost is combined with EBRT, particularly a LDR boost, are of concern in comparison to EBRT alone. HDR brachytherapy boost has many physical properties inherent to its rapid delivery of a large dose which may reduce acute toxicities and also appeal to the radiobiology of prostate cancer. We herein review the evidence for use of either LDR or HDR brachytherapy boost for high-risk prostate cancer and summarize comparisons between the two treatment modalities

Treatment patterns and overall survival outcomes among patients aged 80 yr or older with high-risk prostate cancer

BACKGROUND: Elderly patients diagnosed with high-risk prostate cancer (PCa) present a therapeutic dilemma of balancing treatment of a potentially lethal malignancy with overtreatment of a cancer that may not threaten life expectancy. OBJECTIVE: To investigate treatment patterns and overall survival outcomes in this group of patients. DESIGN SETTING AND PARTICIPANTS: A retrospective cohort study was conducted. We queried the National Cancer Database for high-risk PCa in patients aged 80 yr or older diagnosed during 2004-2016. INTERVENTION: Eligible patients underwent no treatment following biopsy (ie, observation), androgen deprivation therapy (ADT) alone, radiation therapy (RT) alone, RT + ADT, or surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier, log rank, and multivariate Cox proportional hazard regression was performed to compare overall survival (OS). RESULTS AND LIMITATIONS: A total of 19 920 men were eligible for analysis, and the most common treatment approach was RT + ADT (7401 patients; 37.2%). Observation and ADT alone declined over time (59.3% in 2004 vs 47.5% in 2016). There was no observed difference in OS between observation and ADT alone (adjusted hazard ratio [HR] 1.04, 95% confidence interval [CI], 0.99-1.09; CONCLUSIONS: This analysis demonstrates that the use of definitive local therapy, including surgery or RT ± ADT, is increasing and is associated with a 50% reduction in overall mortality compared with observation or ADT alone. While prospective validation is warranted, elderly men with high-risk disease eligible for definitive management should be counseled on the risks, including a possible compromise in OS, with deferring definitive management. PATIENT SUMMARY: Elderly men are more often diagnosed with higher-risk prostate cancer but are less likely to receive curative treatment options than younger men. Our analysis demonstrates that for men ≥80 yr of age with high-risk prostate cancer, definitive local therapy, including surgery or radiation therapy and/or androgen deprivation therapy, is associated with a 50% reduction in overall mortality compared with observation or androgen deprivation therapy alone. We therefore recommend that life expectancy (ie, physiologic age) be taken into account, over chronologic age, and that elderly men with good life expectancy (eg, \u3e5 yr; minimal comorbidity) should be offered definitive, life-prolonging therapy

The association of radiation dose with overall survival for patients treated with prostate stereotactic body radiation therapy

Introduction Stereotactic body radiation therapy (SBRT) for prostate adenocarcinoma (PCa) has demonstrated excellent biochemical recurrence-free survival, with studies showing improved BRFS with higher-dose SBRT. However, current studies have been underpowered to evaluate the relationship of SBRT dose to overall survival (OS). In this retrospective study using the National Cancer Database (NCDB), we hypothesize that, given the low alpha/beta ratio of PCa, a relatively small increase in the dose-per-fraction would be associated with improved survival outcomes for intermediate-risk PCa (IR-PCa) comparing 36.25 Gy/5 fx [biologically equivalent dose (BEDα/β = 1.5 = 211.46 Gy vs. 35 Gy (BED1.5 = 198.33 Gy)]. Materials and methods We queried records from the NCDB from 2005 to 2015 for men receiving prostate SBRT for IR-PCa (n=2673). 82% were treated using either 35 Gy/5 fx or 36.25 Gy/5 fx. We compared OS in men receiving 35 Gy versus 36.25 Gy. Inverse probability of treatment weighting (IPTW) was used to adjust for covariable imbalances. Unweighted- and weighted-multivariable analysis (MVA) using Cox regression was used to compare OS hazard ratios, accounting for age, race, Charlson-Deyo comorbidity score, treatment facility type, prostate-specific antigen (PSA), clinical T-stage, Gleason Score, and use of androgen deprivation therapy (ADT). Kaplan-Meier analysis was performed. Results Seven hundred and eighty men (35%) were treated with 35 Gy/5 fx and 1434 men (65%) were treated with 36.25 Gy/5 fx (n=2214). Compared to 35 Gy, treatment with 36.25 Gy was associated with significantly improved OS (hazard ratio [HR]: 0.61 [95% CI: 0.43-0.89]

Effectiveness of postoperative radiotherapy after radical cystectomy for locally advanced bladder cancer

BACKGROUND: Local-regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity/mortality. Postoperative radiotherapy (PORT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of PORT would improve OS in LABC in a large nationwide oncology database. METHODS: We identified ≥ pT3pN0-3M0 LABC patients in the National Cancer Database diagnosed 2004-2014 who underwent RC ± PORT. OS was calculated using Kaplan-Meier and Cox proportional hazards regression modeling was used to identify predictors of OS. Propensity matching was performed to match RC patients who received PORT vs those who did not. RESULTS: 15,124 RC patients were identified with 512 (3.3%) receiving PORT. Median OS was 20.0 months (95% CI, 18.2-21.8) for PORT vs 20.8 months (95% CI, 20.3-21.3) for no PORT (P = 0.178). In multivariable analysis, PORT was independently associated with improved OS: hazard ratio 0.87 (95% CI, 0.78-0.97); P = 0.008. A one-to-three propensity match yielded 1,858 patients (24.9% receiving PORT and 75.1% without). In the propensity-matched cohort, median OS was 19.8 months (95% CI, 18.0-21.6) for PORT vs 16.9 months (95% CI, 15.6-18.1) for no PORT (P = 0.030). In the propensity-matched cohort of urothelial carcinoma patients (N = 1,460), PORT was associated with improved OS for pT4, pN+, and positive margins (P \u3c 0.01 all). CONCLUSION: In this observational cohort, PORT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of PORT in selected patients with LABC, regardless of histology. Prospective trials of PORT are warranted

Treatment patterns of high-dose-rate and low-dose-rate brachytherapy as monotherapy for prostate cancer

Purpose: Monotherapy with high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy are both recommended modalities for prostate cancer. The choice between HDR and LDR is dependent on patient, physician, and hospital preferences. We sought to identify treatment patterns and factors associated with receipt of HDR or LDR monotherapy. Material and methods: We queried the National Cancer Database (NCDB) for patients with localized low- or intermediate-risk prostate cancer treated with HDR or LDR monotherapy. Descriptive statistics were used to analyze patterns of HDR vs. LDR. Patient characteristics were correlated with HDR vs. LDR using multivariable logistic regression. Results: We identified 50,326 patients from 2004-2014: LDR 37,863 (75.2%) vs. HDR 12,463 (24.8%). Median follow-up was 70.3 months. The overall use of monotherapy declined over time. HDR application declined relative to LDR. In 2004, 27.0% of cases were HDR compared to 19.2% in 2014. Factors associated with increased likelihood of HDR on multivariable analysis included: increasing age (OR: 1.01, 95% CI: 1.01-1.01), cT2c disease (OR: 1.25, 95% CI: 1.11-1.41), treatment at an academic center (OR: 2.45, 95% CI: 2.24-2.65), non-white race (OR: 1.34, 95% CI: 1.27-1.42), and income \u3e $63,000 (OR: 1.73, 95% CI: 1.59-1.88). LDR was more common in 2010-2014 (OR: 0.59, 95% CI: 0.54-0.65), Charlson-Deyo comorbidity index \u3e 0 (OR: 0.89, 95% CI: 0.84-0.95), and for patients receiving hormone therapy (OR: 0.88, 95% CI: 0.83-0.93). No difference in prostate-specific antigen (PSA) or Gleason score and receipt of HDR vs. LDR was observed. Mean overall survival was 127.0 months for HDR and 125.4 for LDR, and was not statistically different. Conclusions: We observed an overall decrease in brachytherapy (BT) monotherapy use since 2004 for localized prostate cancer. Despite similar survival outcomes, the use of HDR monotherapy declined relative to LDR