Efficacy of brachytherapy for prostate cancer in African Americans compared with Caucasians

PURPOSE: To compare the biochemical response to prostate brachytherapy between African Americans and Caucasians in a consecutive series of patients treated at a single institution. METHODS AND MATERIALS: Between July 1995 and October 2001, 173 patients were treated with permanent (125)I seed implantation alone for presumed localized adenocarcinoma of the prostate. Twelve patients were African American and their biochemical response to treatment was compared with the 161 Caucasian patients. The patients were evaluated for biochemical recurrence according to the ASTRO consensus statement and for achieving and maintaining PSA nadirs of < or = 1.0, < or = 0.5, and < or = 0.2. Median pretreatment PSA level was 8 for the African American group and 6 for the Caucasian group. Median Gleason score for each group was 6 and no patients had palpable extraprostatic disease at the time of treatment. RESULTS: None of the African American patients have experienced biochemical recurrence compared with 7.5% of the Caucasian patients (p=0.34). The percentage of African American patients achieving and maintaining a PSA level of < or = 1.0 was 83% compared with 89% for the Caucasian patients (p=0.61). PSA nadir of < or = 0.5 was achieved in 75% of the African American patients and 81% of the Caucasian patients (p=0.52) and 50% of the African American patients experienced PSA levels of < or = 0.2 compared with 59% of the Caucasian patients (p=0.88). CONCLUSION: African American patients with prostate cancer have in general been reported to have worse prognosis compared with Caucasians. This series suggests similar outcome between African American and Caucasian patients treated with brachytherapy for prostate cancer.     

Prostate-specific antigen bounce in patients treated before 60 years old by iodine 125 brachytherapy for prostate cancer is frequent and not a prognostic factor

PurposeThe only prognostic factor of prostate-specific antigen (PSA) bounce in prostate cancer found in several studies is young age but has never been specifically studied in this subset of patients for long-term results. Bounce characteristics, histological, clinical, and dosimetric data in young patients were analyzed, as well as their impact on toxicity and survival.Material and MethodsThis retrospective study included patients aged ≤60 years treated with exclusive iodine 125 brachytherapy with low or intermediary prostate adenocarcinoma during 1999–2014. Exclusion criteria were a follow-up of ≤24 months. PSA bounce was defined as a ≥0.2-ng/mL increase above the interval PSA nadir, followed by a decrease to nadir or below.ResultsThis study analyzed 179 patients. Median age was 56 years (46–59 years). The median follow-up was 79 months (54; 123). The bounce incidence was 56.8% (49.6%; 64.2%) at 5 years, inversely proportional to positive/total biopsies ratio (HR 0.98, 95% CI [0.97, 0.99]). Incidence of biochemical failure was 1.2%, 95% CI (0.3%; 4.7%), at 5 years with no difference between the bounce and no-bounce group (HR 0.96, 95% CI [0.25; 3.58]). Bounce is an unfavorable prognostic factor for grade two and three urinary toxicities 6.67 (4.14; 10.76) (p < 0.001).ConclusionsPSA bounce is common in young people after brachytherapy. It should be monitored without starting an inadequate and sometimes invasive relapse checkup or a relapse 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.     

Cesium-131 prostate brachytherapy: A single institutional long-term experience

AimsTo report on the PSA outcomes in men undergoing prostate seed implant (PSI) with Cesium-131 at a single institution.Materials and MethodsAll patients who underwent prostate brachytherapy with Cesium-131 (¹³¹Cs) at our institution and had the potential for at least 24 months of follow up were included in this study. Results are reported for the by NCCN risk group (low, low/high-intermediate, and high), as well as by treatment received (monotherapy, combination external beam radiation + PSI, or trimodal therapy with androgen deprivation). The Phoenix definition (absolute nadir plus 2 ng/mL) was used to define biochemical freedom from disease (BFD).ResultsEight hundred and six men have undergone prostate brachytherapy with Cesium-131 at our institution, and 669 men were included in analysis. Median follow up was 60.0 months (range: 0–144 months). According to NCCN risk categories, 29.9% were low-, 55.6% intermediate-, and 14.5% high-risk. Using the Phoenix criteria, 5/10-year BFD was 97.1/95.3% for patients in the low-risk category, 94.0/90.1% for patients in the intermediate-risk category, and 86.2/56.6% for patients in the high-risk category. PSA ≤0.2 ng/dL at 4 years was predictive of 10 year biochemical control: 96.3% vs 70.4%, p < 0.001.ConclusionsThe present study demonstrates that prostate brachytherapy with ¹³¹Cs achieves excellent long-term biochemical control.     

Risk factors for biochemical recurrence after a tissue-ablative prostate-specific antigen <0.2 ng/mL

PurposeA prostate-specific antigen (PSA) nadir <0.2 ng/mL is generally considered as tissue ablative and at low risk for recurrence. After attaining such a low PSA nadir, we analyzed risk factors for recurrence.Methods and materialsWe identified patients from our institutionalized database with either D'Amico low- or intermediate-risk prostate cancer that was treated with either low-dose-rate prostate brachytherapy or external beam radiotherapy as monotherapy. We compared patients who attained a nadir <0.2 ng/mL and subsequently developed biochemical failure to patients who did not experience biochemical failure by using χ² test and Student t test. Survival analysis was performed using the Kaplan–Meier method (log-rank test).ResultsOf 892 patients, 560 (63%) achieved a nadir <0.2 ng/mL. Only 23 (4.1%) later developed a biochemical recurrence. The 7-year Kaplan–Meier biochemical recurrence-free survival after a PSA nadir of <0.2 ng/mL was 96%. Patients who later experienced biochemical recurrence were more likely to have Cancer of the Prostate Risk Assessment Score intermediate- or high-risk cancer: (74% vs. 40%, p < 0.001). Patients were more likely to have a diagnostic PSA >6.0 ng/mL: (66% vs. 43% p < 0.001) and have a Gleason score ≥ 3  + 4: (52% vs. 34%, p = 0.005). They were also more likely to be older (p = 0.003): mean (SD) 70.3 (6.4) vs. 66.2 (6.5) and have a time to PSA nadir that was significantly shorter (p = 0.013): mean (SD) 51.8 (29.6) vs. 65.2 (25.1).ConclusionsBiochemical recurrence after attaining a PSA nadir <0.2 ng/mL is rare and more frequent in patients with intermediate risk cancer and older patients. These patients can benefit from a prolonged followup with specialized physicians.     

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.     

Comparison of dose-escalated,image-guided radiotherapy vs. dose-escalated,high-dose-rate brachytherapy boost in a modern cohort of intermediate-risk prostate cancer patients

PurposeWe compared outcomes in intermediate-risk prostate cancer patients treated with dose-escalated adaptive image-guided radiation therapy (IGRT) or dose-escalated high-dose-rate brachytherapy boost (HDR-B).Methods and MaterialsPatients with intermediate-risk prostate cancer by National Comprehensive Cancer Network criteria were treated with either CT-based off-line adaptive IGRT (n = 734) or HDR-B (n = 282). IGRT was delivered with 3D-conformal or intensity-modulated radiation therapy with a median dose of 77.4 Gy. For HDR-B, the whole pelvis received a median 46 Gy, and the prostate 2 implants of 9.5 Gy (n = 71), 10.5 Gy (n = 155), or 11.5 Gy (n = 56).ResultsMedian followup was 3.7 years for IGRT and 8.0 years for HDR-B (p < 0.001). Eight-year biochemical control was 86% for IGRT and 91% for HDR-B (p = 0.22), disease-free survival 67% for IGRT and 79% for HDR-B (p = 0.006), and overall survival 75% for IGRT and 86% for HDR-B (p = 0.009). Cause-specific survival (8-year, 100% vs. 99%), freedom from distant metastases (98% vs. 97%), and freedom from local recurrence (98% vs. 98%) did not differ (p > 0.50 each). A worse prognosis group was defined by percent positive prostate biopsy cores >50%, perineural invasion, or stage T2b–c, encompassing 260 (35%) IGRT and 171 (61%) HDR-B patients. These patients evidenced a 5-year biochemical control of 96% for HDR-B and 87% for IGRT (p = 0.002).ConclusionsDose-escalated IGRT and HDR-B both yield excellent clinical outcomes for patients with intermediate-risk prostate cancer. Improved biochemical control with HDR-B for patients with worse pretreatment characteristics suggests that a subgroup of intermediate-risk prostate cancer patients may benefit from dual-modality treatment.     

Relationship between prostate-specific antigen bounce body fat distribution and body mass index in permanent seed brachytherapy for prostate cancer

PurposeTo analyze the influence of body mass index (BMI) and adipose tissue distribution on prostate-specific antigen (PSA) bounce after iodine-125 prostate brachytherapy.Methods and MaterialsWe studied 20 patients who had PSA bounce (≥0.50 ng/mL) after exclusive prostate brachytherapy. These patients were compared with 48 patients without a bounce (<0.50 ng/mL). All patients in the comparison group had a followup of ≥24 months and a last PSA ≤0.5 ng/mL. Within these 48 patients, there was a group matched for age (n = 20). Univariate and multivariate logistic models were estimated to assess the association between age, baseline PSA, prostate volume, D₉₀, visceral fat (VF) volume, and BMI on PSA-bouncing status.ResultsWhen comparing the patients with a bounce to those without, only BMI showed a significantly different distribution (mean, 25.18 vs. 27.47 kg/m²; p = 0.0342). On a multivariate analysis, BMI had an odds ratio of 0.85 (95% confidence interval, 0.71–0.99, p = 0.049), indicating that an increase of 1 kg/m² in BMI is associated with a 15% reduction in the odds of having a bounce. In the univariate analysis with the matching patients, BMI was a significant predictor of a bounce (p = 0.0147). In the multivariate conditional logistic model, BMI showed a trend toward an influence on a bounce (p = 0.0615). All other factors, including VF, did not have any influence on a PSA bounce.ConclusionsPatients with a lower BMI are more likely to experience a PSA bounce ≥0.50 ng/mL. VF did not have an influence on a PSA bounce.     

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.     

Transperineal mapping biopsy improves selection of brachytherapy boost for men with localized prostate cancer

PURPOSETo determine if transperineal mapping biopsy (TPMB) can improve the selection of brachytherapy alone (BT) or brachytherapy boost (BTB) in men with localized prostate cancer.Methods and MaterialsTwo hundred and eighteen men underwent TPMB with a mean of 48.6 cores retrieved. Comparisons were made between prebiopsy risk features and biopsy results to treatment choice with associations tested with ANOVA (bootstrap), χ² test (Pearson), and linear regression. Survival estimates were tested by the Kaplan–Meier method with comparisons by log rank.ResultsMean age, prostate specific antigen (PSA), prostate specific antigen density (PSAD), and prostate volume were 67.2 years, 8.1 ng/mL, 0.19, and 50.3 cc, respectively. 105 (48.2%) biopsies were positive for Gleason Group (GG) 1: 34 (32.4%), 2: 21 (20%), 3: 31 (29.5%), 4: 7 (6.7%), and 5: 12 (11.4%). The mean number of positive cores (PCs) was 7.3 (median 6, range 1–37). Men with six or more PCs had higher PSA (11.3 vs. 6.0 ng/mL, p = 0.025) and PSAD (0.34 vs. 0.13, p = 0.013). Overall brachytherapy was used in 74 (70.5%) as either monotherapy or boost therapy. Men with BTB had higher PSA (9.7 vs. 6.7 ng/mL, p = 0.029), PSAD (0.27 vs. 0.16, p = 0.007), GG (3.3 vs. 1.8, p < 0.001), more bilateral disease (75.9% vs. 55.6%, odds ratio 3.9, p = 0.008), and PCs (10.9 vs. 4.4, p < 0.001). On linear regression, only GG (p = 0.008) and PCs (p = 0.044) were associated with BTB. Biochemical-free failure at 5 years was 92.7%.ConclusionsTPMB improves the selection of patients for BTB. Men with more PCs are more likely to have BTB. Restricting the need for BTB to those with greater volume prostate cancer may reduce radiation side effects.     

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.     

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.     

PSA outcomes and late toxicity of single-fraction HDR brachytherapy and LDR brachytherapy as monotherapy in localized prostate cancer: A phase 2 randomized pilot study

PURPOSETo evaluate the PSA outcomes and the late patient's reported health related quality of life (HRQOL) and toxicity after single-fraction High-Dose-Rate brachytherapy (HDRB) and Low-Dose-Rate brachytherapy (LDRB) for prostate cancer.METHODSMen with low and favorable intermediate-risk prostate cancer across 3 centres were randomized between monotherapy brachytherapy with either Iodine-125 LDRB or 19 Gy single-fraction HDRB. Biochemical outcomes were evaluated using the Phoenix definition, PSA nadir and absolute PSA value <0.4 ng/mL. Toxicities and HRQOL were recorded at 24 and 36 months.RESULTSA total of 31 patients were randomized, 15 in the LDRB arm and 16 patients in the HDRB arm. After a median follow-up of 45(36–53) months, 3 patients in the HDRB arm experienced biochemical failure (p = 0.092). Nineteen Gy single-fraction HDRB was associated with significantly higher PSA nadir compared to LDRB (1.02 ± 0.66vs 0.25 ± 0.39, p < 0.0001). Moreover, a significantly larger proportion of patients in the LDRB group had a PSA <0.4 ng/mL (13/15 vs 2/16, p < 0.0001). For late Genito-Urinary, Gastro-Intestinal, and sexual toxicities at 24 and 36 months, no significant differences were found between the 2 arms. As for HRQOL, the IPSS and EPIC-26 urinary irritative score were significantly better for patients treated with HDRB over the first 36 months post-treatment (p = 0.001 and p = 0.01, respectively), reflecting superior HRQOL.CONCLUSIONHDRB resulted in superior HRQOL in the irritative urinary domain compared to LDRB. PSA nadir was significantly lower in the LDRB group and a higher proportion of patients in the LDRB group reached PSA <0.4 ng/mL.     

Pride or prejudice: Does Phoenix flatter radiation therapy?

PurposeTo compare disease-free survival (DFS) rates using a >0.4 ng/mL biochemical failure definition with the Phoenix (nadir+2 ng/mL) failure definition by analyzing a consecutive cohort of 1006 patients treated with low-dose-rate prostate brachytherapy (LDR-PB) monotherapy.Methods and MaterialsData for first 1006 consecutive LDR-PB implants (1998–2003) were extracted from a prospective database. Patients had low- (58%) or intermediate (42%)-risk disease. Three months neoadjuvant and 3 months concomitant androgen deprivation therapy were used in 65% of cases. The Phoenix definition was modified to “unfail” patients who had a benign prostate-specific antigen (PSA) bounce.ResultsThe median followup is 7.5 years. The median PSA at latest followup for disease-free patients was 0.04 ng/mL. The Phoenix definition yielded 5- and 10-year Kaplan–Meier DFS estimates of 96.5 ± 1.2% and 93.7 ± 2.0%, respectively. Applying the >0.4 ng/mL threshold reduced these estimates to 94.4 ± 1.6% and 88.8 ± 3.0% (log rank, p = 0.015).ConclusionsCompared with Phoenix, applying a >0.4 ng/mL failure definition increased biochemical failure by ∼2% at 5 years and ∼5% at 10 years. These data show that Phoenix did not greatly exaggerate DFS estimates compared with a surgical-type threshold. However, this observation is a consequence of the exceptionally low residual PSA values characteristic of LDR-PB and cannot be generalized to other forms of radiation therapy.     

Permanent prostate brachytherapy monotherapy with I-125 for low- and intermediate-risk prostate cancer: Outcomes in 974 patients

Purpose

To report outcomes of patients undergoing low-dose-rate (LDR) brachytherapy and investigate factors associated with biochemical failure and survival.

Unusually high prostate-specific antigen bounce after prostate brachytherapy: Searching for etiologic factors

PurposeDetermine whether fat distribution, body mass index, or clinical and dosimetric factors are associated with prostate specific antigen (PSA) bounce (PSAb) of ≥1.6 ng/mL in patients treated with permanent seed ¹²⁵I prostate brachytherapy (PB).Methods and MaterialsWe identified 23 patients with a PSAb of ≥1.6 ng/mL. For each patient with a bounce, at least one control with similar age (age ± 2 years, n = 31) was identified. Control patients had to have no bounce (≤0.2 ng/mL) and a most recent PSA of <1 ng/mL. CT at Day 30 after PB was used to determine the volume of subcutaneous adipose tissue, visceral adipose tissue, and peri-prostatic fat. Univariate and multivariate logistic models were used to assess the association between PSAb and adipose tissue distribution and clinical and dosimetric factors.ResultsMean patient age was 62.3 ± 5.3 years. Mean PSAb height was 2.7 ± 0.8 ng/mL, and mean time to bounce was 9.6 ± 4 months. More than 90% of the patients reached a PSA nadir before PSAb within 12 months post-PB. Patients showing PSAb were more likely to have a T1c disease vs. T2a (odds ratio = 18.87; 95% confidence interval: 2.32–454.55; p = 0.019) and a lower seed activity per cc of prostate volume (odds ratio = 0.02; 95% confidence interval = 0.42–2.22; p = 0.026). Neither fat distribution nor body mass index was associated with PSAb (p = 0.11–0.597).ConclusionsClinical and dosimetric factors play a role in PSAb of ≥1.6 ng/mL. Fat distribution is not associated with a PSAb. There is presently no satisfactory theory to explain the etiology of PSAb.     

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%.     

Medium-term oncological and functional outcomes of hemi-gland brachytherapy using iodine-125 seeds for intermediate-risk unilateral prostate cancer

PURPOSETo examine medium-term outcomes of hemi-gland low-dose-rate brachytherapy as a primary treatment for intermediate-risk prostate cancer.METHODSWe recruited intermediate-risk unilateral prostate cancer patients for a prospective trial of hemi-gland brachytherapy. Twenty-four patients underwent hemi-gland iodine-125 seed implantation with a prescribed dose of 160 Gy. Serum prostate-specific antigen (PSA) was measured regularly and follow-up biopsy was scheduled after 2–3 years of treatment. When clinically needed afterward, for-cause biopsy was performed to confirm pathology. Treatment failure (TF)-free survival, which was defined as freedom from radical or systemic therapy, metastases, and cancer-specific mortality, was assessed, as was biochemical failure (BF)-free survival. Urinary and sexual functions were also evaluated.RESULTSMedian follow-up duration was 61 months. Twenty-two patients (92%) exhibited a declining trend or decreased value of PSA for 12 months or longer after the treatment. Follow-up biopsy in the initial triennium and for-cause biopsy in the subsequent triennium were performed in 16 and four patients, respectively, and cancer was found from the treated lobe in one patient (4% of the cohort) and significant cancer was found from untreated lobes in four patients (17%) in total. Secondary treatments were performed in six patients successfully. Five-year freedom from BF, TF, and metastasis was 71%, 90%, and 100%, respectively. The International Prostate Symptom Score significantly deteriorated at 3 months and reversed itself afterward. The International Index of Erectile Function 5 had no significant decrease.CONCLUSIONSHemi-gland low-dose-rate brachytherapy provides favorable medium-term oncological outcomes with genito-urinary functional preservation for men with intermediate-risk unilateral prostate cancer.     

PSA bounce after prostate brachytherapy with or without neoadjuvant androgen deprivation

PurposeTo assess the impact of PSA bounce (PB) on biochemical failure (BF) and clinical failure (CF) in brachytherapy patients treated with or without neoadjuvant androgen deprivation (AD).Methods and MaterialsFrom 1987 to 2003, 691 patients with clinical stage T1–T3N0M0 prostate cancer were treated with external beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy boost (n = 407), HDR brachytherapy alone (n = 93), or permanent seed implant (n = 191). Three hundred seventeen patients (46%) received neoadjuvant/adjuvant AD with RT. BF was scored using 3 definitions (ASTRO—3 rises, nadir + 2 ng/ml, and threshold 3 ng/ml) based on current and absolute nadir (AN) methodologies. PB was defined as any increase in PSA followed by a decrease to the prior baseline or lower. The median followup was 4.0 years.ResultsForty-six patients (7%) experienced CF at 5 years. PB of ≥0.1, ≥1.0, and ≥2.0 ng/ml at any time after RT occurred in 330 (48%), 60 (9%), and 22 patients (3%) respectively. The use of an AN definition reduced the likelihood of scoring PB as BF across all levels. The patients receiving AD experienced significantly longer bounce duration. Bounce <1.0 ng/ml showed no association with CF. For bounce ≥1.0 ng/ml, 10% demonstrated CF vs. 6% without bounce of this amplitude (p = 0.27). Bounces ≥1.0 ng/ml were more likely to be scored as BFs for definitions based on current nadir (3 rises: 20% vs. 13%, nadir + 2: 43% vs. 11%, 3 at/after nadir: 57% vs. 12%) than those based on AN (3 rises: 8% vs. 10%, nadir + 2: 18% vs. 11%, 3 at/after nadir: 13% vs. 11%).ConclusionsBounces ≥1.0 ng/ml are rare after brachytherapy with or without neoadjuvant AD, occurring in less than 10% of patients. Low PBs have little impact on BF, but as PB amplitude increases, the BF rate increases. BF definitions based on AN are less sensitive to PB after brachytherapy.     

Prognostic importance of tobacco use in men receiving definitive prostate brachytherapy

PurposeSeveral prominent publications have identified an overall association between tobacco use and an increased risk of disease recurrence and disease-specific mortality in prostate cancer patients. The authors explored whether tobacco use adversely impacts treatment outcomes in men treated with permanent interstitial brachytherapy.Methods and MaterialsFrom April 1995 to August 2008, 2057 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.5 years. The role of tobacco use as a prognostic factor for biochemical progression-free survival, cause-specific survival, and overall survival was investigated. Differences in survival between smokers and nonsmokers were compared using Kaplan–Meier curves and log-rank tests.ResultsCurrent smokers presented with a lower body mass index (p < 0.001), smaller prostate size (p = 0.003), younger age (p < 0.001), higher prostate-specific antigen level (p = 0.002), a trend toward higher percentage biopsy core involvement (p = 0.08), higher incidence of perineural invasion (p = 0.015), and higher risk disease (p < 0.001) than former or nonsmokers. There was no difference in biochemical progression-free survival (p = 0.30) or cause-specific survival (p = 0.72) at 10 years for smokers compared with nonsmokers. On univariate and multivariate analysis, tobacco use was an adverse risk factor for overall survival (p < 0.001). There was no association between smoking and any prostate cancer-specific outcome.ConclusionsSmokers treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men who are nonsmokers.