Single-fraction brachytherapy as monotherapy for early-stage prostate cancer: The UCSF experience

PurposeHigh-dose-rate (HDR) brachytherapy as monotherapy is an effective treatment option for localized prostate cancer, but experience with single-fraction brachytherapy is limited by studies with small sample size. We report a large single-institution experience with single-fraction HDR brachytherapy as monotherapy for early-stage prostate cancer.Methods and MaterialsRetrospective chart review was performed for men treated with HDR brachytherapy as monotherapy for low- to intermediate-risk prostate cancer. Competing risk analyses were performed to estimate subdistribution hazard ratio and cumulative incidence of biochemical recurrence (BCR) and prostate cancer–specific mortality.ResultsWe identified 124 men with a median followup of 2.2 years (interquartile range 25th to 75th percentile: 1.8–3). Overall, 21.0% of patients (n = 26) were low risk, 44.4% (n = 55) were favorable intermediate risk, and 34.7% (n = 43) were unfavorable intermediate risk. At 2 years, the cumulative incidence of BCR was 3.5%: 0% for low risk, 4.0% for favorable intermediate risk patients, and 4.5% for unfavorable intermediate risk patients. In total, 12 BCRs were observed (9.7%) and approximately half occurred after median followup of 2.2 years. Compared with low-risk and favorable intermediate-risk disease, unfavorable intermediate-risk disease was significantly associated with BCR (subdistribution hazard ratio: 3.6, 95% CI: 1.1 to 11.1, p = 0.03). Prostate cancer–specific mortality was 0%. No patient experienced Grade 3 or higher acute or late genitourinary toxicity.ConclusionsSingle-fraction brachytherapy for early-stage prostate cancer was safe with promising short-term disease control rates, especially for low-risk patients. Longer term followup is needed as we observed an overall BCR rate of 9.7%.     

Influence of transitioning of planning techniques in high-dose-rate brachytherapy monotherapy for clinically localized prostate cancer from two- to three-dimensional planning

PurposeThe purpose of this study was to examine the influence of transitioning treatment planning techniques in high-dose-rate interstitial brachytherapy monotherapy for localized prostate cancer.Methods and MaterialsWe compared 113 patients treated with initial two-dimensional treatment planning (2D: 74% received 54 Gy/nine fractions) to 240 patients treated with three-dimensional planning (3D: 70 CT image-guided 3D [CT-3D]: 84% 45.5 Gy/seven fractions and 170 MRI image-guided [MRI-3D]: 87% received 49 Gy/nine fractions).ResultsThe actuarial 5-year biochemical failure-free survival rates for 2D and 3D planning were 88.4% and 95.1% (p = 0.0285 between 2D and 3D) (89.4% in CT-3D and 97.5% in MRI-3D), respectively; the rates for 2D and 3D planning were not available and 100% in the low-risk group (100% and 100%), 97.7% and 94.5% (p = 0.7626) (85.1% and 100%) in the intermediate-risk group, and 82.5% and 94.4% (p = 0.0507) (93.8% and 94.7%) for the high-risk group. Late gastrointestinal (GI) toxicity Grade 1, Grade 2, and Grade 3 was found in 13%, 4%, and 1% in 2D, whereas 8%, 2%, and 0% in 3D group (p = 0.0699), respectively. 3D decreased GI toxicity Grade 2 ≤ than 2D (19% and 10%, p = 0.0169). Late genitourinary toxicity Grade 1, Grade 2, and Grade 3 was 21%, 12%, and 3% for 2D and 32%, 18%, and 3% for 3D, respectively (p = 0.0217).ConclusionsThe 3D technique has the potential to reduce GI toxicity and improve biochemical control rate compared to 2D planning, whereas 3D resulted in increased mild genitourinary toxicity.     

Long-term efficacy and urological toxicity of low-dose-rate brachytherapy (LDR-BT) as monotherapy in localized prostate cancer

PurposeThe purpose of this study was to evaluate the incidence of late severe (≥Grade 3) urinary toxicity and the long-term efficacy after low-dose-rate brachytherapy (LDR-BT) in patients with localized prostate cancer (PCa).Methods and MaterialsDuring the years 1999–2008, 241 patients with PCa who underwent LDR-BT with I¹²⁵ and were followed up in Kuopio University Hospital were included to this analysis. The incidence of late severe (Grade 3) urinary toxicity and the long-term efficacy results were analyzed.ResultsAll D'Amico risk groups were represented, as 58.9%, 35.3%, and 5.8% of the patients were classified as low-, intermediate-, and high-risk patients, respectively. With a median followup of 11.4 years after implantation, the incidence of severe urinary toxicity increased throughout the followup period. The risk of Grade 3 urinary toxicity was highest among patients with higher Gleason scores (p = 0.016) and higher initial urine residual volumes (p = 0.017) and the cumulative incidence of severe urinary toxicity was 10.0%. The crude rate for transurethral prostatic resection was 5.8%. The relapse-free survival, the cause-specific survival, and the overall survival were 79.3%, 95.0%, and 66.4%, respectively.ConclusionsThe treatment was well tolerated as 90% of patients avoided any Grade 3 urinary toxicity. LDR-BT for localized PCa achieved high and durable efficacy. These results support the role of LDR-BT monotherapy as one of the valid primary treatment options for low-risk and favorable intermediate-risk patients.     

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.     

After ASCENDE-RT: Biochemical and survival outcomes following combined external beam radiotherapy and low-dose-rate brachytherapy for high-risk and unfavourable intermediate-risk prostate cancer,a population-based analysis

PURPOSETo evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB).METHODS AND MATERIALSA population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial.RESULTSThe median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p < 0.001), 73 ± 8% (p < 0.001), and 77 ± 9% (p = 0.098) for the ineligible patients.CONCLUSIONSIn this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.     

Intraprostatic calcification and biochemical recurrence in men treated with cesium-131 prostate brachytherapy

PURPOSEBaseline intraprostatic calcification (IC) has been shown to be associated with a higher rate of biochemical recurrence (BCR) in men treated with iodine-125 prostate brachytherapy (PB). We evaluated this association in a cohort of men treated with cesium-131 PB.METHODS AND MATERIALSWe retrospectively reviewed the charts of all low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- external beam radiotherapy (EBRT) at our institution from 2/2011 to 7/2018. Patients with < 24 months of follow up or those who received androgen deprivation therapy were excluded. Baseline IC status (defined as one or more ICs ≥ 5 mm) was determined on post-PB CT scans. Cox analysis was used to assess predictors of BCR and Kaplan–Meier survival curves were calculated.RESULTSTwo hundred and sixteen low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- EBRT were included. Median follow up was 56.9 months (range 24.1–111.4). Overall, 76 (35.2%) patients had baseline IC and 140 (64.8%) did not. Baseline disease characteristics did not differ significantly between groups. On univariate Cox analysis, only risk group (p = 0.047) and initial PSA (p = 0.016) were significant predictors of BCR, whereas baseline IC was not (p = 0.11). The 5-year BCR-free survival in patients with versus without baseline IC was 97.7% versus 93.8% (p = 0.405), respectively.CONCLUSIONSIn a cohort of low- and intermediate-risk prostate cancer patients treated with cesium-131 PB, the rate of BCR in men with baseline IC was low and baseline IC was not associated with a higher risk of BCR.     

Radiobiological optimization comparison between pulse-dose-rate and high-dose-rate brachytherapy in patients with locally advanced cervical cancer

PurposeOnly scarce data are available on the possibility to include radiobiological optimization as part of the dosimetric process in cervical cancer treated with brachytherapy (BT). We compared dosimetric outcomes of pulse-dose-rate (PDR) and high-dose-rate (HDR)-BT, according to linear-quadratic model.Methods and MaterialsThree-dimensional dosimetric data of 10 consecutive patients with cervical cancer undergoing intracavitary image-guided adaptive PDR-BT after external beam radiation therapy were examined. A new HDR plan was generated for each patient using the same method as for the PDR plan. The procedure was intended to achieve the same D₉₀ high-risk clinical target volume with HDR as with PDR planning after conversion into dose equivalent per 2 Gy fractions (EQD2) following linear-quadratic model. Plans were compared for dosimetric variables.ResultsAs per study's methodology, the D₉₀ high-risk clinical target volume was strictly identical between PDR and HDR plans: 91.0 Gy (interquartile: 86.0–94.6 Gy). The median D₉₈ intermediate-risk clinical target volume was 62.9 Gy_EQD2 with HDR vs. 65.0 Gy_EQD2 with PDR (p < 0.001). The median bladder D_2cc was 65.6 Gy_EQD2 with HDR, vs. 62 Gy_EQD2 with PDR (p = 0.004). Doses to the rectum, sigmoid, and small bowel were higher with HDR plans with a median D_2cc of 55.6 Gy_EQD2 (vs. 55.1 Gy_EQD2, p = 0.027), 67.2 Gy_EQD2 (vs. S 64.7 Gy_EQD2, p = 0.002), and 69.4 Gy_EQD2 (vs. 66.8 Gy_EQD2, p = 0.014), respectively. For organs at risk (OARs), the effect of radiobiological weighting depended on the dose delivered. When OARs BT contribution to D_2cc doses was <20 Gy_EQD2, both BT modalities were equivalent. OARs EQD2 doses were all higher with HDR when BT contribution to D_2cc was ≥20 Gy_EQD2.ConclusionBoth BT modalities provided satisfactory target volume coverage with a slightly higher value with the HDR technique for OARs D2_cc while intermediate-risk clinical target volume received higher dose in the PDR plan. The radiobiological benefit of PDR over HDR was predominant when BT contribution dose to OARs was >20 Gy.     

Biochemical outcomes and toxicities in young men with prostate cancer after permanent iodine-125 seed implantation: Prospective cohort study in 6662 patients

PURPOSEWe evaluated the effect of age, <60 and ≥60 years, on biochemical outcomes and toxicities in patients with prostate cancer who underwent permanent seed implantation (PI) ± external beam radiation therapy ± hormone therapy in a national Japanese prospective cohort study (J-POPS).METHODS AND MATERIALSThe safety and efficacy analyses included 6721 and 6662 patients, respectively. We categorized patients into two age groups: <60 (n = 716) and ≥60 (n = 6,005) years. We used propensity score matching (PSM) to estimate the marginal effect of age on biochemical freedom from failure (bFFF) using a Phoenix definition and Cox proportional hazard models.RESULTSThe median followup period was 60.0 months. Without PSM, men <60 years demonstrated similar 5-year bFFF (96.3%) compared with men ≥60 years (95.6%; p = 0.576); percent positive biopsies, biologically effective dose, Gleason score, risk classification, and supplemental external beam radiation therapy (p <0.001, <0.001, <0.001, 0.008, and <0.001) were significantly associated with bFFF while age was not (p = 0.576). With PSM, bFFF was not significantly different between age groups (p = 0.664); however, men <60 years showed a significantly lower incidence of declining erectile function, grade ≥2 all urinary toxicities, urinary frequency/urgency, and rectal bleeding (p <0.001, 0.024, 0.031, and 0.010) than men ≥60 years.CONCLUSIONSAfter PI, men <60 years achieved a comparable 5-year biochemical control rate and showed a lower incidence of several toxicities compared to men ≥60 years. This suggests that PI should be an excellent treatment option for men <60 years with prostate cancer.     

Declining brachytherapy utilization for high-risk prostate cancer—Can clinical pathways reverse the trend?

PurposeAlthough external beam radiation therapy (EBRT) plus a brachytherapy boost (BB) offers a 20% improvement in biochemical progression-free survival compared with dose-escalated EBRT alone for men with intermediate and high-risk prostate cancer, population studies show a concerning decline in BB utilization.MethodsWe modified our clinical pathway (CP) in January 2016 to indicate EBRT with BB as first-choice modality for high-risk prostate cancer, based on preliminary findings of Androgen Suppression Combined with Elective Nodal and Dose-Escalated Radiation Therapy. A retrospective review was performed on 659 patients with high-risk prostate cancer treated with definitive intent EBRT ± BB within a network of 19 sites between December 2011 and July 2017. χ² test was used to determine changes in practice pattern before vs. after CP modification.ResultsBefore CP modification, 25.2% of patients were planned for BB, compared with 45.4% afterward (p < 0.001). Among 23 nonbrachytherapist physicians, utilization of BB increased from 3.4% to 14.8% (p < 0.001) after CP modification. Among nine brachytherapists, utilization increased from 46.4% to 55.6% (p = 0.120). Among patients treated by a nonbrachytherapist who did not receive BB, the reason was physician preference in 59.7%, patient preference in 19.9%, and other in 20.4%.ConclusionBased on recent evidence suggesting improved biochemical progression-free survival with use of BB for high-risk prostate cancer, we modified our CP, after which we observed increased use of a BB across a network, especially among physicians who do not perform brachytherapy. However, physician preference remains the most significant factor in the nonutilization of BB. New mechanisms are needed to overcome this barrier.     

MRI-based sector analysis enhances prostate palladium-103 brachytherapy quality assurance in a phase II prospective trial of men with intermediate-risk localized prostate cancer

PurposePalladium-103 (¹⁰³Pd) may be superior to other isotopes in brachytherapy for localized intermediate-risk prostate cancer because of its relatively short half-life, higher initial dose rate, and greater dose heterogeneity within the target volume; these properties also underscore the need for accurate target delineation and postimplant quality assurance. We assessed the use of prostate sector analysis based on MRI for quality assurance after ¹⁰³Pd monotherapy.Methods and MaterialsFifty men with intermediate-risk prostate cancer underwent ¹⁰³Pd monotherapy in a prospective phase II trial at MD Anderson Cancer Center. Dosimetric analyses on day 30 after the implant were done using both CT and fused CT/MRI scans. Dosimetric variables were assessed for the entire prostate and for each of three or six sectors. Volumes and dosimetric variables were compared with paired t tests.ResultsPostimplant dosimetric variables for the entire prostate were significantly different on CT vs. CT/MRI (p = 0.019 for V₁₀₀ and p < 0.01 for D₉₀). Prostate volumes were smaller on the CT/MRI scans (p < 0.00001). The base sector contributed the greatest difference, with doses based on CT/MRI lower than those based on CT (p < 0.01 for V₁₀₀ and D₉₀). To date, these lower base doses have not affected biochemical outcomes for patients with disease in prostate base biopsy samples.ConclusionsCT/MRI is more precise than CT for prostate volume delineation and dosimetric quality assessment and thus provides superior heterogeneity control assessment after ¹⁰³Pd monotherapy implants.     

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.     

Sector analysis of dosimetry of prostate cancer patients treated with low-dose-rate brachytherapy

PurposeBrachytherapy is an effective single treatment modality for low- and intermediate-risk prostate cancer. Here, we compare the radiation doses in different prostate sectors between the preimplant planning images and the postimplant dosimetry.Methods and MaterialsTwo hundred fifteen consecutive patients treated for prostate cancer by ¹²⁵I seed brachytherapy were assessed. Pretreatment plans using transrectal ultrasound images of the prostate were compared with the dose calculated on posttreatment MRI and CT scans obtained 1 month after seed implantation. Twelve sectors were generated by dividing the prostate base, midgland, and apex into four quadrants each. Pretreatment and posttreatment dosimetry were compared between the 12 different sectors of the prostate.ResultsAverage V₁₀₀ (percentage of prostate volume that receives 100% of the prescribed dose) in the preimplant planning images of the prostate was 99.9 ± 0.25% compared with postimplant V₁₀₀ of 94.8 ± 3.77% (p < 0.0001). Prostate V₁₀₀ in the postimplant dosimetry was >91% in all sectors, except the anterior base sector, in which it was 64.87 ± 20.96%. Average 1-month D₉₀ (the dose to 90% of the prostate volume) was 114.5 ± 10.55%. D₉₀ at 1 month compared with preimplant planning was lower in the prostate base and higher in the prostate apex (p < 0.001).ConclusionsOur results show that in ¹²⁵I seed brachytherapy, prostate base receives a lower dose and apex receives a higher dose compared with preimplant planned dose coverage.     

Dose to the dominant intraprostatic lesion using HDR vs. LDR monotherapy: A Phase II randomized trial

PurposeTo present the dosimetric results of a Phase II randomized trial comparing dose escalation to the MRI-defined dominant intraprostatic lesion (DIL) using either low-dose-rate (LDR) or high-dose-rate (HDR) prostate brachytherapy.Material and MethodsPatients receiving prostate brachytherapy as monotherapy were randomized to LDR or HDR brachytherapy. Prostate and DILs were contoured on preoperative multiparametric MRI. These images were registered with transrectal ultrasound for treatment planning. LDR brachytherapy was preplanned using I-125 seeds. HDR brachytherapy used intraoperative transrectal ultrasound–based planning to deliver 27 Gy/2 fractions in separate implants. DIL location was classified as peripheral, central, or anterior. A student t-test compared DIL D₉₀ between modalities and DIL locations.ResultsOf 60 patients, 31 underwent LDR and 29 HDR brachytherapy. Up to three DILs were identified per patient (100 total) with 74 peripheral, six central, and 20 anterior DILs. Mean DIL volume was 1.9 cc (SD: 1.7 cc) for LDR and 1.6 cc (SD 1.3 cc) for HDR (p = 0.279). Mean DIL D₉₀ was 151% (SD 30%) for LDR and 132% (SD 13%) for HDR. For LDR, mean peripheral DIL D₉₀ was 159% (SD 27%) and central or anterior 127% (SD 13%). HDR peripheral DILs received 137% (SD 12%) and central or anterior 119% (SD 7%). DIL D₉₀ for peripheral lesions was higher than anterior and central (p < 0.001).ConclusionsDIL location affects dose escalation, particularly because of urethral proximity, such as for anterior and central DILs. HDR brachytherapy may dose escalate better when target DIL is close to critical organs.     

The use of supplemental external beam radiotherapy in men with low-risk prostate cancer undergoing brachytherapy before and after the 1999 American Brachytherapy Society Guideline statement

PurposeIn 1999, the American Brachytherapy Society (ABS) recommended brachy-monotherapy for men with low-risk prostate cancer because of the potential for increased toxicity with combined external beam radiotherapy (EBRT) and brachytherapy without the proof of increased efficacy. We investigated the patterns of care in the community in this patient population before and after the reporting of the ABS guideline.Methods and MaterialsThe study cohort consisted of 4943 men (median age, 69.0 years) with low-risk prostate cancer treated with brachytherapy with or without supplemental EBRT from 1991 to 2007 across 21 community radiation oncology centers. Multivariable logistic regression analysis was performed to determine if there was a significant association between the year of brachytherapy, prostate-specific antigen level, clinical tumor (T) category, patient's age, and the use of supplemental EBRT.ResultsSupplemental EBRT was used in 647 men (13%). The EBRT use initially increased until 2001 and then decreased yielding a significant association (adjusted odds ratio [AOR], 0.92; p < 0.001) between the EBRT use and the year of brachytherapy using a quadratic formulation. Specifically, EBRT use peaked at 24.6% in 2001 and subsequently declined to 3.3% by 2007. Men with clinical category T2a as compared with T1c disease (AOR, 1.43; p < 0.001) were more likely to receive combined modality therapy.ConclusionsThe use of supplemental EBRT in men with low-risk prostate cancer treated with brachytherapy has decreased since 2001. This change in practice patterns suggests gradual adoption of the 1999 ABS practice guidelines.     

Assessing the impact of brachytherapy boost and androgen deprivation therapy on survival outcomes for patients with unfavorable intermediate-risk prostate cancer patients treated with external beam radiotherapy

BACKGROUNDCurrent recommendations regarding radiotherapy treatment for unfavorable intermediate-risk prostate cancer (UIR-PCa) include external beam radiotherapy (EBRT) ± brachytherapy boost (BT) ± androgen deprivation therapy (ADT). The ideal radiotherapy treatment approach for UIR-PCa has not been well-defined. We hypothesized that EBRT+BT±ADT is associated with improved overall survival (OS) relative to EBRT±ADT in men with UIR-PCa.MATERIALS AND METHODSThe National Cancer Database (NCDB) was used to retrospectively identify 32,246 men diagnosed between 2004 and 2015 with UIR-PCa who received EBRT (n = 13,265), EBRT+ADT (n = 13,123), EBRT+BT (n = 3440), or EBRT+BT+ADT (n = 2418). OS was the primary outcome. Inverse probability of treatment weighting was used to adjust for covariable imbalances and weight-adjusted multivariable analysis using Cox regression modeling was used to compare OS hazard ratios.RESULTSMedian follow-up was 60 months (range: 3–168 months). EBRT+ADT correlated with improved OS relative to EBRT alone on multivariable analysis (Hazard Ratio (HR): 0.92, [95% Confidence Interval: 0.87–0.98], p = 0.005). Compared to EBRT+ADT, EBRT+BT (HR: 0.77 [0.69–0.85], p = 3 × 10^?7) and EBRT+BT+ADT (HR: 0.75 [0.67–0.83], p = 6 × 10^?8) were associated with improved OS. Eight-years OS for the EBRT+ADT versus EBRT+BT+ADT was 70% and 78% (p < 0.0001), which is similar to historical clinical trials (ASCENDE-RT 9-year OS: 74% vs. 78%, p = 0.29). Relative to EBRT+BT, EBRT+BT+ADT was not associated with improved OS (HR: 0.99 [0.87–1.11], p = 0.82).CONCLUSIONSIn a large retrospective cohort, the addition of brachytherapy to EBRT correlated with improved survival in men with UIR-PCa. Men receiving EBRT+ADT+BT had improved OS relative to EBRT+ADT. The addition of ADT to EBRT, but not to EBRT+BT, correlated with improved OS.     

PSA: Declining utilization of prostate brachytherapy

PURPOSETo analyze rates of brachytherapy use for prostate cancer over time and evaluate patient characteristics, demographics and factors predictive for its utilization.METHODSData was retrospectively analyzed from the National Cancer Database (NCDB) for patients with localized prostate cancer treated between 2010 and 2015. Patients were included if they had biopsy confirmed localized adenocarcinoma of the prostate, were treated with radiation as definitive local therapy, and were at least 18 years old. Utilization rates of external beam radiation (EBRT), brachytherapy (BT) and combination (EBRT + BT) were evaluated over time. Univariable (UVA) and backwards elimination multivariable (MVA) analysis were performed to determine characteristics predictive for brachytherapy use.RESULTSWe analyzed 178,837 patients with localized adenocarcinoma of the prostate treated between 2010 and 2015 with radiation therapy. During this period, the use of EBRT increased from 67% to 78%, BT (both monotherapy and combination with EBRT) decreased from 33% to 22%, BT monotherapy decreased from 25% to 16% and EBRT + BT decreased from 8% to 6%. Age >70, government funded insurance or lack of insurance, intermediate or high-risk disease and treatment at an academic center were associated with significantly lower utilization of brachytherapy (all p <0.001), while higher median zip code income was associated with increased use (p = 0.02). On multivariable analysis patients who were younger, had private insurance, were lower NCCN risk category and treated in non-academic cancer centers, had a higher rate of brachytherapy utilization. Notably, on both UVA and MVA brachytherapy practice decreased with increasing year of diagnosis (OR 0.881, 95% CI 0.853–0.910, p <0.001).CONCLUSIONRates of brachytherapy utilization for the treatment of prostate cancer continue to decrease over time. Treatment at an academic center was associated with reduced likelihood of brachytherapy use. This has significant implications for the training of future radiation oncology residents/fellows and direct consequences for both our patients and healthcare expenditure.     

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.     

Changes in ADC and T2-weighted MRI-derived radiomic features in patients treated with focal salvage HDR prostate brachytherapy for local recurrence after previous external-beam radiotherapy

PurposeTo explore the changes in T2-weighted (T2w) and apparent diffusion coefficient (ADC) magnetic resonance imaging -derived radiomic features of the gross tumor volume (GTV) from focal salvage high-dose-rate prostate brachytherapy (HDRB) and to correlate with clinical parameters.Materials and MethodsEligible patients included those with biopsy-confirmed local recurrence that correlated with MRI (T2w, ADC). Patients received 27 Gy in 2 fractions separated by 1 week to a quadrant consisting of the GTV. The MRI was repeated 1 year after HDRB. GTVs, planning target volumes, and normal prostate tissue control volumes were identified on the pre- and post-HDRB MRIs. Radiomic features from each GTV were extracted, and principle component analysis identified features with the highest variance.ResultsPre- and post-HDRB MRIs were obtained from 14 trial patients. Principle component analysis showed that 18 and 17 features contributed to 93% and 86% of the variance observed in the T2w and ADC data, respectively. Sixteen T2w features and 1 ADC GTV feature were different from the control volumes in the pre-HDRB images (p < 0.05). Ten T2w and 7 ADC GTV post-HDRB features were different from those of pre-HDRB (p < 0.05).ConclusionsExploratory analysis reveals several radiomic features in the T2w and ADC image GTVs that distinguish the GTV from healthy prostate tissue and change significantly after salvage HDRB.