An age-corrected matched-pair study of erectile function in patients treated with dose-escalated adaptive image-guided intensity-modulated radiation therapy vs. high-dose-rate brachytherapy for prostate cancer

PurposeTo compare erectile dysfunction (ED) after adaptive dose-escalated image-guided intensity-modulated radiotherapy (IG-IMRT) and high-dose-rate interstitial brachytherapy (HDR) monotherapy.Methods and MaterialsLow- and intermediate-risk prostate cancer patients treated with IG-IMRT or HDR were matched on pretreatment ED, age, Gleason score, T-stage, and prostate specific antigen. Patients who received androgen deprivation therapy were excluded. ED was graded by Common Terminology Criteria for Adverse Events v4. Actuarial rates of ED were computed by the Kaplan–Meier method.ResultsThere were 384 patients with median followup of 2.0 years (0.5–6.1) for IG-IMRT and 2.0 years (0.5–8.7) for HDR. The median IG-IMRT dose was 75.6 Gy and HDR dose 38 Gy in four fractions. For patients with no pretreatment ED, actuarial rates of requiring intervention (Grade ≥2 ED) at 3 years were 31% for IG-IMRT and 19% for HDR (p = 0.23), and impotence despite medical intervention (Grade 3) were 0% for IG-IMRT and 6% for HDR (p = 0.06). For patients with Grade 1 pretreatment ED, Grade ≥2 ED at 3 years were 47% for IG-IMRT and 34% for HDR (p = 0.79), and Grade 3 ED were 15% in both groups (p = 0.59). For patients with Grade 2 pretreatment ED, Grade 3 ED at 3 years were 22% for IG-IMRT and 37% for HDR (p = 0.70). No variables were predictive of Grade ≥2 ED following treatment.ConclusionsRates of ED requiring medical intervention for both IG-IMRT and HDR are low and equivalent. Even patients with ED before treatment are likely to maintain potency with medication use at 3 years following treatment.     

Manual vs. automated implantation of seeds in prostate brachytherapy: Oncologic results from a single-center study

PurposeThe objective of this study was to study survival and tolerance of prostate cancer patients treated with ¹²⁵I permanent interstitial brachytherapy by automated vs. manual implantation of seeds.Methods and MaterialsBetween 2002 and 2010, 349 selected patients were treated with ¹²⁵I brachytherapy by the same team: from 2002 to April 2005, 65 patients with linked seeds and then 284 patients treated using Nucletron First System automated implantation. We analyzed biochemical recurrence-free survival (bRFS) rates and toxicities (univariate and multivariate analyses).ResultsTwo hundred seventy-seven (79.4%) and 69 patients (19.8%) with low- and intermediate-risk disease were treated, respectively (median follow-up: 64 months). The 5-year bRFS rate was 93.1% (95% confidence interval 89.3–95.6) for the entire cohort. The 5-year bRFS rates were 93.4% and 91.7% for patients with low- and intermediate-risk disease, respectively (p = 0.42). In univariate and multivariate analyses, there was no statistically significant difference in the 5-year bRFS rate depending on the implantation technique (93.1% vs. 91.8%, respectively, for automated and linked seeds; p = 0.53). In univariate analysis, only D₉₀ prostate (dose delivered to 90% of the prostate) <140 Gy (p = 0.01), lack of prostate-specific antigen bounce (p = 0.008), and nadir prostate-specific antigen >0.11 (p = 0.01) were predictive factors for bRFS. We observed Grade 3 urethritis in 7 patients (2%), urinary incontinence in 2 patients (0.7%), and Grade 4 proctitis in 2 patients (0.7%).ConclusionsIn this large single-center series, brachytherapy for selected localized prostate cancer achieved excellent rates of biochemical control at 5 years (93.1%) with an acceptable toxicity profile, irrespective of the implantation technique used.     

Long-term biochemical control and cause-specific survival in men with Gleason grade Group 4 and 5 prostate cancer treated with brachytherapy and external beam irradiation

PurposeMen with Gleason grade Group (GG) 4 and 5 prostate cancer have high failure rates when treated by conventional therapy. We investigated the effect of higher radiation doses on freedom from biochemical failure (FBF) and prostate cancer mortality (cause-specific survival [CSS]) in men treated with a combination of permanent implant and external beam irradiation (EBRT).Methods and MaterialsThree hundred twenty men with GG4 (n = 186) and 5 (n = 134) prostate cancer were treated with I-125 or Pd-103 implant followed by 45 Gy of EBRT. Radiation doses were converted to the biological equivalent dose (BED). The median age, prostate-specific antigen (PSA), time on hormone therapy, BED, and followup were 69 years, 9.0 ng/mL, 9 months, 210 Gy, and 6.5 years, respectively. FBF and CSS were calculated by Kaplan–Meier method with associations determined by log rank and Cox regression.ResultsTen-year FBF for GG4 vs. 5 was 77.8 vs. 61.3% (p = 0.015), and CSS was 94 vs. 79.3% (p = 0.001). Men with lower PSA had improved FBF and CSS (p < 0.001). Thirty-one of 320 died of prostate cancer of which 10/186 (5.4%) had GG4 and 21/134 (15.7%) GG5 (OR 3.3, p = 0.002). BED <200 Gy was associated with a 2.2× greater BF (p = 0.004) and 2.4× prostate cancer mortality (p = 0.020). Significant covariates on regression analysis for FBF and CSS were PSA (p = 0.014), GG (p = 0.007), BED (p = 0.009), and GG (p = 0.001).ConclusionsSurvival rates for high-grade prostate cancer are favorable when diagnosed in men with lower PSA and treated with doses of BED > 200 Gy. Higher BED is achieved with a combination of I-125 (110 Gy) or Pd-103 (100 Gy) and 45 Gy EBRT.     

Patient-reported health-related quality of life for men treated with low-dose-rate prostate brachytherapy as monotherapy with 125-iodine, 103-palladium,or 131-cesium: Results of a prospective phase II study

PurposeTo compare quality of life (QoL) after brachytherapy with one of the three approved radioactive isotopes.Methods and MaterialsPatients with mostly favorable intermediate-risk prostate cancer were treated on this prospective phase II trial with brachytherapy as monotherapy, without hormonal therapy. QoL was recorded at baseline and each follow-up by using the Expanded Prostate Cancer Index Composite instrument. The minimal clinically important difference was defined as half the standard deviation of the baseline score for each domain. Mixed effect models were used to compare the different isotopes, and time-driven activity-based costing was used to compute costs.ResultsFrom 2006 to 2013, 300 patients were treated with iodine-125 (I-125, n = 98, prescribed dose [PD] = 145 Gy), palladium-103 (Pd-103, n = 102, PD = 125 Gy), or cesium-131 (Cs-131, n = 100, PD = 115 Gy). Median age was 64.9 years. Median follow-up time was 5.1 years for the entire cohort, and 7.1, 4.8 and 3.3 years for I-125, Pd-103, and Cs-131 groups, respectively. All three isotope groups showed an initial drop in QoL at first follow-up, which gradually improved over the first 2 years for urinary and bowel domains. QoL profiles were similar between I-125 and Pd-103, whereas Cs-131 showed a statistically significant decrease in QoL regarding bowel and sexual function at 12 months compared with Pd-103. However, these differences did not reach the minimal clinically important difference. Compared with I-125, the use of Pd-103 or Cs-131 resulted in cost increases of 18% and 34% respectively.ConclusionsThe three different isotopes produced a similar QoL profile. Statistically significant differences favored Pd-103/I-125 over Cs-131 for bowel and sexual QoL, but this did not reach clinical significance.     

I-125 or Pd-103 for brachytherapy boost in men with high-risk prostate cancer: A comparison of survival and morbidity outcomes

PurposeBrachytherapy boost improves biochemical recurrence rates in men with high-risk prostate cancer (HRPC). Few data are available on whether one isotope is superior to another. We compared the oncologic and morbidity outcomes of I-125 and Pd-103 in men with HRPC receiving brachytherapy.Methods and MaterialsOf 797 patients with HRPC, 190 (23.8%) received I-125 or 607 received Pd-103 with a median of 45 Gy of external beam irradiation. Freedom from biochemical failure (FFBF), freedom from metastases (FFMs), cause-specific survival (CSS), and morbidity were compared for the two isotopes by the ANOVA and the χ² test with survival determined by the Kaplan–Meier method and Cox regression.ResultsMen treated with I-125 had a higher stage (p < 0.001), biological equivalent dose (BED) (p < 0.001), and longer hormone therapy (neoadjuvant hormone therapy, p < 0.001), where men treated with Pd-103 had a higher Gleason score (GS, p < 0.001) and longer followup (median 8.3 vs. 5.3 years, p < 0.001). Ten-year FFBF, FFM, and CSS for I-125 vs. Pd-103 were 77.5 vs. 80.2% (p = 0.897), 94.7 vs. 91.9% (p = 0.017), and 95.4 vs. 91.8% (p = 0.346), respectively. Men with T3 had superior CSS (94.1 vs. 79.5%, p = 0.001) with I-125. Significant covariates by Cox regression for FFBF were prostate specific antigen (PSA), the GS, and the BED (p < 0.001), for FFM PSA (p < 0.001) and GS (p = 0.029), and for CSS PSA, the GS (p < 0.001) and the BED (p = 0.022). Prostate cancer mortality was 7/62 (15.6%) for BED ≤ 150 Gy, 18/229 (7.9%) for BED >150–200 Gy, and 20/470 (5.9%) for BED >200 Gy (p = 0.029). Long-term morbidity was not different for the two isotopes.ConclusionsBrachytherapy boost with I-125 and Pd-103 appears equally effective yielding 10-year CSS of over 90%. I-125 may have an advantage in T3 disease. Higher doses yield the most favorable survival.     

Toxicity and early treatment outcomes in low- and intermediate-risk prostate cancer managed by high-dose-rate brachytherapy as a monotherapy

PurposeTo determine the acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and present short-term biochemical no evidence of disease (bNED) rates after high-dose-rate brachytherapy (HDR-B) monotherapy.Methods and MaterialsBetween October 2003 and June 2006, 36 patients with low (28) and intermediate (8) risk prostate cancer (PCA) were treated by HDR-B monotherapy. All patients received one implant and four fractions of 9.5 Gy within 48 h for a total prescribed dose (PD) of 38 Gy. Five patients received hormonal therapy (HT). Median age was 63.5 years and median followup was 3 years (range, 0.4–4 years). Toxicity was scored according to the CTCAE version 3.0. Biochemical failure was defined according to the Phoenix criteria.ResultsAcute and late Grade 3 GU toxicity was observed in 1 (3%) and 4 (11%) patients, respectively. Grade 3 GI toxicity was absent. The three- year bNED survival rate was 100%. The sexual preservation rate in patients without HT was 75%. Late Grade 3 GU toxicity was associated with the planning target volume (PTV) V₁₀₀ (% PTV receiving ≥100% of the PD; p = 0.036), D₉₀ (dose delivered to 90% of the PTV; p = 0.02), and the urethral V₁₂₀ (urethral volume receiving ≥120% of the PD; p = 0.043). The urethral V₁₂₀ was associated with increased PTV V₁₀₀ (p < 0.001) and D₉₀ (p = 0.003).ConclusionsAfter HDR-B monotherapy, late Grade 3 GU toxicity is associated with the urethral V₁₂₀ and the V₁₀₀ and D₉₀ of the PTV. Decrease of the irradiated urethral volume may reduce the GU toxicity and potentially improve the therapeutic ratio of this treatment.     

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer

PurposeRetrospective data suggest less benefit from androgen deprivation therapy (ADT) in the setting of dose-escalated definitive radiation for prostate cancer, especially when a combination of external beam radiotherapy (EBRT) and brachytherapy approaches are used. This study aimed to test the hypothesis that patients with prostate cancer with intermediate- or high-risk disease undergoing extreme dose escalation with a brachytherapy boost are less likely to receive ADT.Methods and MaterialsData from the National Cancer Database were extracted for men aged 40–90 years diagnosed with node-negative, non-metastatic prostate cancer from 2004 to 2015. Only patients with intermediate- or high-risk disease who were treated with definitive radiotherapy were included. The association and patterns of care between dose escalated radiotherapy and ADT receipt were assessed using multivariable logistic regression.ResultsPatients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive ADT if they underwent dose escalation with a combination of EBRT and brachytherapy (odds ratio 0.67, p < 0.0001). Over time, this decrease in ADT utilization has widened for patients with unfavorable intermediate-risk disease. There was no difference in ADT utilization when comparing patients treated with non–dose-escalated EBRT to those treated with dose-escalated EBRT (without brachytherapy).ConclusionIn this large national database, patients with unfavorable intermediate- and high-risk prostate cancer were significantly less likely to receive guideline-indicated ADT if they underwent extreme dose escalation with combined radiation modalities. As we await prospective data guiding the utility of ADT with dose escalated radiation, these findings suggest potential underutilization of ADT in patients at higher risk of advanced disease.     

Long-term outcomes of prostate cancer patients with Gleason pattern 5 treated with combined brachytherapy and external beam radiotherapy

PurposeRecent reports have suggested relatively poor prognosis for prostate cancer patients with Gleason pattern 5 treated with dose-escalated external beam radiotherapy (XRT) and androgen deprivation therapy (ADT). We present the largest series of men with high-risk, Gleason pattern 5 prostate cancer treated with permanent interstitial brachytherapy and XRT.Methods and MaterialsBetween April 1995 and December 2008, 329 consecutive patients with National Comprehensive Cancer Network high-risk disease were treated with permanent interstitial brachytherapy. Most received XRT and ADT. Median followup was 7.2 years. The cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters.ResultsAt 10 years, biochemical progression-free survival, cause-specific survival (CSS), and overall survival for the group of high-risk patients as a whole was 91.1%, 95.5%, and 72.5%, respectively. There was no difference in biochemical progression-free survival between men with and without Gleason pattern 5 (89.7% vs. 91.8%; p = 0.56). However, men with Gleason pattern 5 had lower prostate cancer CSS (90.3% vs. 98.1%; p = 0.011). There was no difference in overall survival comparing men with and without Gleason pattern 5 disease (67.7% vs. 75.4%; p = 0.14).ConclusionsMen with high-risk, Gleason pattern 5 histology treated with brachytherapy and XRT have excellent long-term outcomes, which compare favorably to dose-escalated XRT/ADT series without brachytherapy. Nonetheless, Gleason pattern 5 results in lower CSS than high-risk disease without Gleason pattern 5.     

Knife or needles? A cohort analysis of outcomes after radical prostatectomy or brachytherapy for men with low- or intermediate-risk adenocarcinoma of the prostate

PurposeThe purpose of this study was to evaluate long-term outcomes for men with early stage prostate cancer treated with radical prostatectomy (RP) or brachytherapy (BT) at a single tertiary care center.Methods and MaterialsWe retrospectively analyzed data from 371 men with clinical T1a–T2c disease with prostate-specific antigen level <20 ng/mL and Gleason score (GS) 6–7 who were treated with RP (n = 279) or BT (n = 92) at MD Anderson Cancer Center in 2000–2001. Biochemical recurrence–free survival (BRFS) and prostate cancer–specific survival rates were compared by treatment modality.ResultsThe median followup time was 7.2 and 7.6 years for patients treated with RP and BT, respectively. Disease was upgraded from GS 6 to 7 after central review of the biopsy specimen for 36 men treated with RP (12.9%) and 15 men treated with BT (16.3%). After RP, GS was upgraded in 121 men (43.4%) between the centrally reviewed biopsy and the RP specimen. After RP, 5-year BRFS rates were 96.1% and 90.6% for low- and intermediate-risk disease, respectively (p = 0.003). After BT, 5-year BRFS rates were 92.5% and 95.8% for low- and intermediate-risk disease, respectively (p = 0.017). After RP or BT, 5-year BRFS rates were not significantly different with GS upgraded. Five-year prostate cancer–specific survival rates for patients with upgraded GS were 100% for both RP and BT.ConclusionsExcellent disease control outcomes can be achieved after either RP or BT as monotherapy for men with early stage prostate cancer. Upgrading of GS from 6 to 7, either (3 + 4) or (4 + 3), did not predict for worse outcomes.     

Definitive high-dose-rate endobronchial brachytherapy of bronchial stump for lung cancer after surgery

PurposeThe aim of this work was to evaluate outcomes after definitive high-dose-rate endobronchial brachytherapy (HDR-BT) for lung cancer.Methods and MaterialWe treated 34 patients after surgery for lung cancer, without nodal or distant metastases, with HDR-BT. Two groups were analyzed, one with local recurrence in stump after prior surgery (n = 13) and a second with nonradical primary lobar resection found in histopathologically positive margins (n = 21). There were 27 men and 7 women with a median age of 57.4 years. Twenty-five patients received sole brachytherapy with 4 fractions of 7.5 Gy and 9 received combined treatment consisting of 2 fractions of 6 Gy (HDR-BT) and 50 Gy from external beam radiotherapy. Overall survival time (OS) and overall disease-free survival time (OFS) were compared with prognostic factors.ResultsThe complete local and radiologic response rate evaluated at the first month after HDR-BT was 73.5% (25/34). The partial response rate was 26.5%. OFS time in total group was 17.4 months; OS was 18.8 months. Differences were found in OS between both groups—primary tumor or recurrence (log-rank test, p = 0.048). Differences were not found according to gender (p = 0.36), clinical stage (p = 0.76), histopathology (p = 0.93), treatment dose (p = 0.45), sole or combined treatment (p = 0.16), or grade of remission in week 4 (p = 0.15).ConclusionsHDR-BT of a stump recurrence or after nonradical resection leads to a long-term OS rate in patients with localized lung cancer and could be considered curative. We found no correlations between OS and chosen clinical data; adjuvant HDR-BT gave better results.     

Racial differences in the PSA bounce in predicting prostate cancer outcomes after brachytherapy: Evidence from the Department of Veterans Affairs

PurposeAfrican American men have historically had poorer prostate cancer biochemical and survival outcomes than Caucasians. However, emerging data suggest nononcologic factors drive much of this disparity. Prior evidence has suggested an association between a transient prostate specific antigen (PSA) bounce and improved biochemical control. However, racial differences in this relationship have remained relatively unexplored.Methods and MaterialsWe identified 4477 men treated for low- or intermediate-risk prostate cancer within the U.S. Department of Veterans Affairs (VA) from 2000 to 2010 with brachytherapy alone or in combination with external beam radiotherapy without androgen deprivation. Longitudinal PSA data were used to define to biochemical failure and PSA bounce. Cox proportional hazard models were used explore racial differences in the relationship between the PSA bounce and time to biochemical failure.ResultsThirty-one percent of our sample experienced a PSA bounce, with African Americans more likely to experience a bounce (42%) compared with Caucasians (29%); p < 0.001. Despite this, African Americans had a higher likelihood of biochemical failure (hazard ratio [HR] 1.4; p = 0.006). However, African American men experiencing a PSA bounce were less likely to experience a biochemical failure (HR = 0.64; p = 0.046), whereas this relationship was not statistically significant for Caucasians (HR = 0.78; p = 0.092). On multivariate analysis, African Americans receiving brachytherapy alone were most sensitive to the protective benefit of the PSA bounce (HR = 0.64).ConclusionsA PSA bounce was associated with improved biochemical control among patients receiving brachytherapy as part of their treatment for low- or intermediate-risk prostate cancer at the VA. African American men treated with brachytherapy had a particularly pronounced biochemical control benefit of a PSA bounce.     

Brachytherapy provides comparable outcomes and improved cost-effectiveness in the treatment of low/intermediate prostate cancer

PurposeTo evaluate the cost-effectiveness and outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy compared with intensity-modulated radiation therapy (IMRT) in patients with low/intermediate risk of prostate cancer.Methods and MaterialsOne thousand three hundred twenty-eight patients with low or intermediate risk of prostate cancer were treated with LDR (n = 207), HDR with four fractions (n = 252), or IMRT (n = 869) between January 1992 and December 2008. LDR patients were treated with palladium seeds to a median dose of 120 Gy, whereas HDR patients were treated to a median dose 38.0 Gy (four fractions). IMRT patients received 42–44 fractions with a median dose of 75.6 Gy. Clinical outcomes were compared, including biochemical failure, cause-specific survival, and overall survival.ResultsOverall, no differences in 5-year biochemical control (BC) or cause-specific survival were noted among treatment modalities. The calculated reimbursement for LDR brachytherapy, HDR brachytherapy with four fractions, and IMRT was $9,938; $17,514; and $29,356, respectively. HDR and LDR brachytherapy were statistically less costly to Medicare and the institution than IMRT (p < 0.001), and LDR brachytherapy was less costly than HDR brachytherapy (p = 0.01 and p < 0.001). Incremental cost-effectiveness ratios for cost to Medicare for BC with IMRT were $4045 and $2754 per percent of BC for LDR and HDR brachytherapy, respectively. Incremental cost-effectiveness ratio using institutional cost comparing IMRT with LDR and HDR brachytherapy was $4962 and $4824 per 1% improvement in BC.ConclusionsIn this study of patients with low and intermediate risk of prostate cancer, comparable outcomes at 5 years were noted between modalities with increased costs associated with IMRT.     

New approach of ultra-focal brachytherapy for low- and intermediate-risk prostate cancer with custom-linked I-125 seeds: A feasibility study of optimal dose coverage

PurposeTo present the feasibility study of optimal dose coverage in ultra-focal brachytherapy (UFB) with multiparametric MRI for low- and intermediate-risk prostate cancer.Methods and MaterialsUFB provisional dose plans for small target volumes (<7 cc) were calculated on a prostate training phantom to optimize the seeds number and strength. Clinical UFB consisted in a contour-based nonrigid registration (MRI/Ultrasound) to implant a fiducial marker at the location of the tumor focus. Dosimetry was performed with iodine-125 seeds and a prescribed dose of 160 Gy. On CT scans acquired at 1 month, dose coverage of 152 Gy to the ultra-focal gross tumor volume was evaluated. Registrations between magnetic resonance and CT scans were assessed on the first 8 patients with three software solutions: VariSeed, 3D Slicer, and Mirada, and quantitative evaluations of the registrations were performed. Impact of these registrations on the initial dose matrix was performed.ResultsMean differences between simulated dose plans and extrapolated Bard nomogram for UFB volumes were 36.3% (26–56) for the total activity, 18.3% (10–30) for seed strength, and 22.5% (16–38) for number of seeds. Registration method implemented in Mirada performed significantly better than VariSeed and 3D Slicer (p = 0.0117 and p = 0.0357, respectively). For dose plan evaluation between Mirada and VariSeed, D₁₀₀% (Gy) for ultra-focal gross tumor volume had a mean difference of 28.06 Gy, mean values being still above the objective of 152 Gy. D₉₀% for the prostate had a mean difference of 1.17 Gy. For urethra and rectum, dose limits were far below the recommendations.ConclusionsThis UFB study confirmed the possibility to treat with optimal dose coverage target volumes smaller than 7 cc.     

Salvage brachytherapy for recurrent prostate cancer

PurposeTo evaluate the role of salvage prostate brachytherapy for locally recurrent prostate cancer after external beam radiation alone.Methods and MaterialsSixty-nine consecutive patients treated with salvage brachytherapy after a local failure were analyzed. All patients were found to have pathologic proven recurrent prostate cancer at least 2 years after initial therapy and no regional or distant disease on imaging studies. Pd-103 was used with a prescribed pD₉₀ of 100 Gy. In total, 89.9% of patients received androgen suppression (AS) as part of their salvage therapy. Patients whose prostate-specific antigen >5.0 ng/mL while on AS were considered to have castration resistant prostate cancer (CRPC). Patients on AS >6 months before salvage brachytherapy were considered to have delayed therapy. Patients retreated within 5 years after their initial treatment were considered to have early failures.ResultsTotal median followup after salvage therapy was 5.0 years (0.6–13.7). From the date of salvage, 5-year biochemical control for low-risk patients was 85.6%, intermediate-risk patients 74.8%, and high-risk patients 66%. Five-year biochemical control was 73.8% for non-CRPC and 22% for CRPC cases (<0.001). Including and excluding CRPC cases, early treatment after failure vs. delayed treatment was significantly better (p < 0.05). Chronic adverse events were seen in few patients, with genitourinary Grade 3 toxicity of 8.7% and no genitourinary Grade 4 or gastrointestinal Grade 3 or higher toxicities.ConclusionsA subset of failures after definitive radiation is local in nature, and excellent control is possible with salvage brachytherapy.     

Improving prostate brachytherapy quality assurance with MRI–CT fusion–based sector analysis in a phase II prospective trial of men with intermediate-risk prostate cancer

PurposeWe combined sector analysis with MRI–CT fusion to comprehensively assess postimplant dosimetry after prostate brachytherapy.Methods and MaterialsSubjects were 50 men with intermediate-risk prostate cancer treated with ¹²⁵I brachytherapy in a prospective phase II clinical trial. On Day 30 after the implantation, dosimetry was evaluated in the prostate base, midgland, and apex regions on fused MRI–CT scans and CT scans. Volumes of each sector receiving 100% of the prescribed dose (V₁₀₀) and doses to 90% of each sector (D₉₀) were also calculated on the ultrasonogram used for treatment planning and compared with values derived from CT and fused MRI–CT scans.ResultsFused MRI–CT scans revealed lower-than-expected doses for the whole prostate (V₁₀₀ = 91.3%, D₉₀ = 152.9 Gy) compared with CT scans (98.5% and 183.6 Gy, p < 0.0001) and lower doses to the prostate base (V₁₀₀ = 79%, D₉₀ = 130 Gy) vs. CT (96% and 170 Gy, p < 0.0001). However, lower doses to the prostate base did not adversely affect biochemical outcomes in men with biopsy-proven disease at the base. At a median followup time of 42 months, the mean prostate-specific antigen level for all patients was 0.3 ng/mL, and no patient had experienced biochemical or clinical progression or recurrence.ConclusionsMRI–CT fusion–based sector analysis was feasible and revealed significantly lower doses to the prostate base than doses estimated from CT alone, although this did not affect biochemical outcomes. MRI–CT fusion–based sector analysis may be useful for developing MRI-based dosimetric markers to predict disease outcomes and treatment-related morbidity.     

Using a surgical prostate-specific antigen threshold of >0.2 ng/mL to define biochemical failure for intermediate- and high-risk prostate cancer patients treated with definitive radiation therapy in the ASCENDE-RT randomized control trial

PurposeTo compare biochemical failure using a prostate-specific antigen (PSA) threshold of >0.2 ng/mL to that using Phoenix threshold (nadir+2 ng/mL).Methods and MaterialsAndrogen suppression combined with elective nodal and dose-escalated radiation therapy (the ASCENDE-RT trial) is a randomized control trial in which 276 high-risk and 122 intermediate-risk patients were randomized to (1) a standard arm with 12 months of androgen deprivation therapy, pelvic external beam radiation therapy (EBRT) to 46 Gy, and an EBRT boost (dose-escalated EBRT [DE-EBRT]) to 78 Gy, or (2) an experimental arm which substituted a low-dose-rate prostate brachytherapy boost (LDR-PB). The primary endpoint was biochemical progression-free survival (b-PFS) using the Phoenix threshold. In this reanalysis of ASCENDE-RT, the b-PFS using phoenix is compared to the surgical PSA threshold of >0.2 ng/mL.ResultsCompared to nadir+2 ng/mL, the >0.2 ng/mL PSA threshold doubled the number of relapse events from 69 to 139. However, the increase was confined to the DE-EBRT subjects. The 7-year Kaplan-Meier b-PFS after DE-EBRT declined from 76% using nadir+2 ng/mL to 38% using the >0.2 ng/mL threshold (p < 0.001). Among the LDR-PB subset, there was no significant difference in b-PFS; the 7-year Kaplan-Meier b-PFS was 85% (>0.2 ng/mL) versus 88% (nadir+2 ng/mL) (p = 0.319).ConclusionsReplacing Phoenix with a surgical threshold greatly increased biochemical failure after DE-EBRT boost but had no effect after LDR-PB. As a result of this finding, PSA outcomes after surgery or brachytherapy can be directly compared by using the surgical definition of PSA failure. In this context, a brachytherapy boost appears to produce superior b-PFS compared to contemporary surgical series.     

Early toxicity and health-related quality of life results of high-dose-rate brachytherapy as monotherapy for low and intermediate-risk prostate cancer

PurposeTo determine the acute toxicity and effect on health-related quality of life of a two-fraction regimen of high-dose-rate (HDR) prostate brachytherapy.Methods and materialsPatients with low- or intermediate-risk prostate cancer were treated with HDR brachytherapy as monotherapy in two implants of 13.5 Gy spaced 7–14 days apart. Patients completed International Prostate Symptom Score (IPSS) and Expanded Prostate Index Composite (EPIC) questionnaires at 1, 3, 6, 9, 12, 16, 20, and 24 months after brachytherapy. Proportion of patients in each IPSS category (mild = 0–7, moderate = 8–18, severe = 19+) was evaluated at each of the intervals above. Paired t tests with baseline values were done for IPSS and EPIC scores.ResultsThirty patients were accrued to the study. Median prostate-specific antigen was 8,7 (range 4.1–17.5). T stages were T1c = 65%, T2a = 21%, and T2b = 14%. Twenty-seven percent of patients had a Gleason score of 6 and 73% had a Gleason score of 7. IPSS categories at baseline, 1, 3, 6, 12, and 24 months were mild (81%, 43%, 58%, 62%, 76%, 64%), moderate (19%, 32%, 29%, 30%, 20%, 29%), and severe (0%, 25%, 13%, 7%, 4%, 6%), respectively. There was a significant decrease in EPIC sexual summary scores at 1, 3, 6, and 12 months of 0 points (p < 0.001), 17 points (p = 0.01), 18 points (p = 0.02), and 17 points (p = 0.01), respectively.ConclusionsThis is the first report of this cohort of patients treated with two-fraction HDR monotherapy. This regimen shows rates of toxicity and health-related quality of life that appear acceptable as compared to other treatment modalities. These results are also comparable with other reports with similar treatment regimens.     

Dose to the bladder neck is not correlated with urinary toxicity in patients with prostate cancer treated with HDR brachytherapy boost

PurposeThe purpose of this study was to evaluate whether the dose to bladder neck (BN) is a predictor of acute and late urinary toxicity after high-dose-rate brachytherapy (HDRB) boost for prostate cancer.Methods and MaterialsBetween 2014 and 2016, patients with prostate cancer treated at our institution with external beam radiation therapy and 15 Gy single-fraction HDRB boost for intermediate- and high-risk disease according to D'Amico definition were reviewed. Intraoperative CT scan–based inverse planning and ultrasound-based inverse planning were performed in 173 and 136 patients, respectively. The following structures were prospectively contoured: prostate, urethra, rectum, bladder, and the BN defined as 5 mm around the urethra between the catheter balloon and the prostatic urethra. Dose to the BN was reported only, no constraint was applied. Acute and late urinary toxicity were assessed using the International Prostate Symptom Score (IPSS) and the Common Terminology Criteria for Adverse Events v.4.0. Clinical and dosimetry factors associated with urinary toxicity were analyzed using generalized linear models.ResultsA total of 309 patients with median age of 71 years (range 50–89) were included. Median followup was 25 months (range 0–39 months). Using D'Amico definition, 71% of the patients had intermediate-risk disease, whereas 29% had high-risk disease. The mean pretreatment prostate-specific antigen value was 9.65 ng/mL. The mean pretreatment, after 6 weeks and over 6 months IPSSs were 8.34, 12.14, and 10.02, respectively. Urinary obstruction was reported in 14 cases (4.5%). Pretreatment IPSS (p = 0.003) and prostate volume (p = 0.024) were significantly associated with acute and late urinary toxicity. The dose for the most exposed 2 cc (D_2cc) of BN was not correlated with acute (p = 0.798) or late urinary toxicity (p = 0.859). BN D_2cc was not correlated with urinary obstruction (p = 0.272), but bladder V₇₅ was (p = 0.021).ConclusionsHigh pretreatment IPSS, large prostate volume and bladder V₇₅ were the only predictors of acute and late urinary toxicity after HDRB boost in our study. Although BN D_2cc was associated with acute and late urinary toxicity after low-dose-rate brachytherapy, no correlation was found after HDRB. A prospective study comparing dose to the BN in HDRB monotherapy would validate the impact of BN dose on acute and late urinary toxicity.