Patient-reported long-term rectal function after permanent interstitial brachytherapy for clinically localized prostate cancer

PurposeTo evaluate the effect of permanent interstitial brachytherapy with or without supplemental therapies on long-term rectal function using a patient-administered quality-of-life instrument.Methods and MaterialsOne hundred thirty four of the initial 219 prostate brachytherapy patients who remain alive and have participated in a prospective evaluation of rectal function were mailed the rectal function assessment score (R-FAS). Of the 134 patients, 3 have a colostomy because of colorectal cancer, 2 failed to respond, and 129 (99.2% of eligible patients) returned a completed R-FAS. R-FAS ranges from 0 to 27 with lower scores indicative of better bowel function. Median followup was 14 years. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on bowel function.ResultsFor the current cohort, R-FAS was 3.35, which was comparable to the 1999 (4.29), 2002 (3.92), and 2006 (4.00) surveys. In the 2011 survey, 10 (7.8%), 17 (13.1%), and 102 (78.3%) patients reported bowel function to be worse, improved, or unchanged after brachytherapy. No patient has developed a rectal ulcer or fistula. The number of preimplant bowel movements, tobacco, and diabetes mellitus correlated with R-FAS. Consistent with the previous thee surveys, patient’s perception of overall rectal quality of life was inversely related to the use of supplemental external beam radiation.ConclusionsLong-term rectal function after prostate brachytherapy is favorable with a small number of patients reporting deterioration in bowel function. The judicious use of supplemental external beam radiation with particular attention to rectal doses may further improve long-term function.     

Favorable preservation of erectile function after prostate brachytherapy for localized prostate cancer

PurposeWe analyzed the rate of preserved potency after prostate brachytherapy (PB) with radioactive seeds and the impact of patient comorbidities on post-PB erectile dysfunction (ED).MethodsWe included 627 patients who were assessed for pre- and postimplant potency between 2005 and 2017. Assessment was based on the Common Terminology Criteria for Adverse Events Scale (CTCAEs). Logistic regression models were used to assess clinical predictors of preserved potency after PB defined as having sufficient erections for sexual activity with or without the need of oral pharmacologic assistance. Covariates included age, diabetes (DM), hypertension (HTN), dyslipidemia (DLP), coronary artery disease (CAD), International Prostate Symptom Score (IPSS), prostate volume, and Cancer of the Prostate Risk Assessments (CAPRA) score. Patients on androgen deprivation therapy or using five alpha reductase inhibitors were excluded from analyses.ResultsPost-PB potency was assessed at an average of 6 months (n = 627), 1 year (n = 538), 2 years (=440), 4 years (n = 272), and 5 years (n = 124). At 2 and 5 years, post-PB potency was preserved in 87% and 84% of patients, respectively. When adjusting for all available covariates, advanced age, pre-PB potency, and the presence of vascular comorbidities (HTN, DM, and DLP) were all predictors of potency at 2 years after PB (all p < 0.01). When performing a sensitivity analysis for vascular comorbidities, the presence of DM had the strongest impact on ED than either HTN or DLP (p < 0.01).ConclusionMore than 84% of patients had preserved potency 5 years after PB. Advanced age, pre-PB potency, and vascular comorbidities had a statistically significant impact on potency after PB.     

Salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy

PURPOSE: To determine the toxicity and clinical outcome of salvage prostate brachytherapy for localized prostate cancer failure after external beam radiation therapy. METHODS AND MATERIALS: Twenty-one patients underwent (103)Pd salvage brachytherapy (median minimum peripheral dose, 90Gy) after local failure after external beam radiation (median dose, 66.6Gy) from 1/21/1998 to 4/5/2005. The median age was 72 years. Six patients had prior transurethral resection of the prostate. The median Gleason score was 7 and the median preimplant prostate-specific antigen was 3.8. Twelve patients received concurrent androgen ablation with prostate brachytherapy. Biochemical failure was defined as three consecutive rises in prostate-specific antigen scored at the call date, initiation of hormone therapy, or clinical failure. Toxicity was defined according to the National Cancer Institute common toxicity criteria and the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme. RESULTS: With a median followup of 36 months, the actuarial 3-year and 5-year overall survival rates were 81% and 81%, and the biochemical failure-free survival rates were 94% and 38%, respectively. There was no significant difference in biochemical failure-free survival (p=0.98) and overall survival (p=0.13) for patients who had androgen ablation. Four patients developed biochemical failure and 1 patient developed distant metastasis at 59 months from treatment. Four patients had Grade 2 genitourinary adverse events, 2 patients had Grade 1 genitourinary adverse events, and 1 patient had a Grade 2 gastrointestinal adverse event. There were no Grade 3 or higher adverse events. All three deaths were secondary to other medical comorbidities. CONCLUSIONS: Salvage prostate brachytherapy after external beam radiation failure can be safely performed with acceptable biochemical control. This treatment option should be considered for patients who have prolonged life expectancy after localized external beam radiation failure.     

Equivalent uniform dose, D(90), and V(100) correlation with biochemical control after low-dose-rate prostate brachytherapy for clinically low-risk prostate cancer

PURPOSE: To assess the correlation of postimplant dosimetric quantifiers with biochemical control of prostate cancer after low-dose-rate brachytherapy. MATERIALS AND METHODS: Generalized equivalent uniform dose (EUD), dose in Gy to 90% of the prostate gland (D(90)), and percentage of the prostate receiving 100% of the prescribed dose (V(100)) were calculated from the postimplant dose-volume histogram (DVH) for 140 patients undergoing low-dose-rate prostate brachytherapy (LDRPB) monotherapy from 1997 to 2003 at Duke University and the Durham VA Medical Center. Biochemical recurrence was defined according to the American Society for Therapeutic Radiology and Oncology consensus definition. RESULTS: Median followup after LDRPB was 50 months. There was a 7% biochemical recurrence rate (10/140) at last clinical followup. The median EUD was 167 Gy (range, 41-245). The median D(90) was 139 Gy (range, 45-203). The median V(100) was 88% (range, 44-100). The overall 5-year biochemical recurrence-free survival (bRFS) was 94.2%. The 5-year bRFS was 100% for EUD> or =167 Gy and 89.4% for EUD <167 Gy (p=0.008); 100% for D(90) > or =140 Gy and 90.4% for D(90) <140 Gy (p=0.020); 100% for V(100) > or =88%; and 90.3% for V(100) <88% (p=0.017). There was no statistically significant correlation between any of these factors and overall survival. CONCLUSIONS: In our series of 140 patients with low-risk prostate cancer treated with LDRPB alone, we observed a statistically significant correlation between EUD, D(90), and V(100) and bRFS. The generalized EUD, a calculated value that incorporates the entire prostate DVH, appears to be at least as well correlated with bRFS as D(90) or V(100), and may more completely represent the totality of the dose distribution.     

Subclinical inflammation as a predictor for erectile dysfunction after brachytherapy for localized prostate cancer

PURPOSE: Neutrophil-to-lymphocyte ratio (NLR), a marker for subclinical inflammation, has been previously shown to be associated with erectile dysfunction (ED). We studied the potential predictive value of the NLR on ED after prostate brachytherapy (PB) for PCa.METHODS AND MATERIALS: Between July 2005 and January 2021, 842 patients were included in this retrospective study of a prospectively maintained database. ED was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) physician-reported scale. ED was defined as a Grade 2 or 3 function. NLR count was determined 1–2 months before PB and separated into values PB <2 and ≥2. Patient characteristics and erectile function at last follow-up were compared for patients with a Univariate and multivariate analyses were performed to evaluate the predictive value of baseline NLR ≥2 on post-PB ED.RESULTS: Baseline NLR ≥2 was found to be a statistically significant predictor of post-PB ED on both univariate (p = 0.002) and multivariate analyses (p = 0.008). Furthermore, the difference in ED prevalence between the NLR <2 and NLR ≥2 groups became more pronounced with longer follow-up after PB. The ED rate at 5 years post-PB was 43% for the NLR ≥2 groups, compared to 29% for the NLR <2 groups.CONCLUSIONS: Subclinical systemic inflammation is a potentially important factor for predicting sexual toxicity after pelvic radiotherapy. NLR may be used as a proxy for predicting post-PB ED.     

103Pd brachytherapy versus radical prostatectomy in patients with clinically localized prostate cancer: a 12-year experience from a single group practice

PURPOSE: In an effort to shed light on the continuing debate over the best treatment options for patients with localized prostate cancer, we present a retrospective review of patients from a single group community urology practice. METHODS AND MATERIALS: Data from 1707 patients were reviewed. These patients, with T1 or T2 adenocarcinoma of the prostate, were treated from 1992 to 2004 with either brachytherapy or radical retropubic prostatectomy (RRPP); 81% were aged over 65 years. Patients were classified into risk groups based on initial prostate-specific antigen (PSA) and Gleason score. Time to PSA-indicated recurrence was used as the measure of disease control and cure. RESULTS: Time to PSA-indicated recurrence was used as a measure of efficacy. Brachytherapy with 103Pd exclusively and RRPP were found to provide equivalent control (<0.4 ng/mL for prostatectomy and <3 successive rises in PSA as defined by the American Society for Therapeutic Radiology and Oncology [ASTRO]) in low-risk groups (89% seeds vs. 94% RRPP). In intermediate (89% seeds vs. 58% RRPP) and high-risk (88% seeds vs. 43% RRPP) groups, brachytherapy patients had better control rates. The addition of external radiation, with or without luteinizing hormone-releasing hormone therapy, improved biochemical control rates in intermediate and high-risk brachytherapy groups. CONCLUSION: The results failed to show any superiority of prostatectomy over brachytherapy with 103Pd (TheraSeed; Theragenics Corp., Buford, GA) regarding time until relapse as indicated by PSA level increase (>0.4 ng/mL for prostatectomy and >3 successive rises in PSA as defined by ASTRO). We recently reviewed our techniques and improved equipment from 1995 to present and found major gains with both brachytherapy and surgery. Low risk brachytherapy resulted in 99% freedom from PSA failure while surgery showed results of 97%. Brachytherapy and prostatectomy should be offered without bias to all men with stage T1 and T2 organ-confined prostate cancer.     

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%.     

Clinical outcomes of high-dose-rate brachytherapy and external beam radiotherapy in the management of clinically localized prostate cancer

PurposeTo report prostate-specific antigen (PSA) relapse-free survival and treatment-related toxicity outcomes after combining high-dose-rate (HDR) brachytherapy with external beam radiotherapy (EBRT) for patients with clinically localized prostate cancer.Methods and MaterialsBetween 1998 and 2009, 229 patients were treated with HDR brachytherapy followed 3 weeks later by supplemental EBRT. The HDR brachytherapy boost consisted of three fractions of ¹⁹²Ir (5.5–7.5 Gy per fraction), and EBRT consisted of intensity-modulated radiotherapy delivering an additional 45.0–50.4 Gy directed to the prostate gland and seminal vesicles. Median follow-up was 61 months.ResultsSeven-year PSA relapse-free survival for low-, intermediate-, and high-risk patients were 95%, 90%, and 57%, respectively (p < 0.001). Among high-risk patients treated with biological equivalent doses in excess of 190 Gy, 7-year PSA relapse-free survival was 81%. In multivariate analysis, Gleason scores of ≥8 predicted for increased risk of biochemical failure, whereas the use of short-term neoadjuvant androgen deprivation therapy did not influence tumor-control outcomes even among intermediate- or high-risk patients. Seven-year incidence of distant metastases for low-, intermediate-, and high-risk patients were 5%, 3%, and 17%, respectively. Seven-year incidence of late Grade 2 and 3 genitourinary toxicities were 22.1% and 4.9%, respectively and the 7-year incidence of Grade 2 and 3 gastrointestinal toxicities were 1% and 0.4%, respectively.ConclusionHDR prostate brachytherapy in conjunction with supplemental EBRT results in excellent biochemical relapse-free survival rates with a low incidence of severe late genitourinary or gastrointestinal toxicities. The use of short-term neoadjuvant androgen deprivation did not influence long-term biochemical tumor control in this cohort.     

Iodine-125 brachytherapy for prostate cancer: first published Australian experience

With the emergence of new imaging and implant techniques, prostate brachytherapy has become increasingly popular over the last decade. Brachytherapy promises to deliver twice the biologically effective dose as conventional external beam treatments without increasing the dose to tissues surrounding the prostate. However, there are few or no published Australian series of its efficacy in the clinic. We present the experience of one of the first centres in Australia to offer this service to its patients: a series from Sir Charles Gairdner Hospital in Western Australia. We present data on the efficacy of brachytherapy in maintaining prostate specific antigen levels, as well as the rate of urinary, rectal and sexual complications. Our results compare favourably with other brachytherapy and external beam treatment series. We believe that with the increasing trend towards dose escalation and novel therapies, standardized measurements of success and failure need to be better defined, and that randomized trials comparing modalities are needed to improve the management of prostate cancer.     

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.     

LDR vs. HDR brachytherapy for localized prostate cancer: the view from radiobiological models

PURPOSE: Permanent LDR brachytherapy and temporary HDR brachytherapy are competitive techniques for clinically localized prostate radiotherapy. Although a randomized trial will likely never be conducted comparing these two forms of brachytherapy, a comparative radiobiological modeling analysis proves useful in understanding some of their intrinsic differences, several of which could be exploited to improve outcomes. METHODS AND MATERIALS: Radiobiological models based upon the linear quadratic equations are presented for fractionated external beam, fractionated (192)Ir HDR brachytherapy, and (125)I and (103)Pd LDR brachytherapy. These models incorporate the dose heterogeneities present in brachytherapy based upon patient-derived dose volume histograms (DVH) as well as tumor doubling times and repair kinetics. Radiobiological parameters are normalized to correspond to three accepted clinical risk factors based upon T-stage, PSA, and Gleason score to compare models with clinical series. Tumor control probabilities (TCP) for LDR and HDR brachytherapy (as monotherapy or combined with external beam) are compared with clinical bNED survival rates. Predictions are made for dose escalation with HDR brachytherapy regimens. RESULTS: Model predictions for dose escalation with external beam agree with clinical data and validate the models and their underlying assumptions. Both LDR and HDR brachytherapy achieve superior tumor control when compared with external beam at conventional doses (<70 Gy), but similar to results from dose escalation series. LDR brachytherapy as boost achieves superior tumor control than when used as monotherapy. Stage for stage, both LDR and current HDR regimens achieve similar tumor control rates, in agreement with current clinical data. HDR monotherapy with large-dose fraction sizes might achieve superior tumor control compared with LDR, especially if prostate cancer possesses a high sensitivity to dose fractionation (i.e., if the alpha/beta ratio is low). CONCLUSIONS: Radiobiological models support the current clinical evidence for equivalent outcomes in localized prostate cancer with either LDR or HDR brachytherapy using current dose regimens. However, HDR brachytherapy dose escalation regimens might be able to achieve higher biologically effective doses of irradiation in comparison to LDR, and hence improved outcomes. This advantage over LDR would be amplified should prostate cancer possess a high sensitivity to dose fractionation (i.e., a low alpha/beta ratio) as the current evidence suggests.     

Experience of brachytherapy using I-125 seed permanent implants for localized prostate cancer

PURPOSE: We report here our experience of brachytherapy using I-125 seeds for localized prostate cancer in 100 patients. MATERIALS AND METHODS: We carried out brachytherapy with I-125 seed permanent implants in 100 patients with localized prostate cancer between September 2003 and October 2004. Preplanning dosimetry was done using transrectal ultrasonic images obtained three or four weeks prior to treatment. Using transrectal ultrasound, we inserted I-125 seeds in the prostate through needles according to the preplanning diagram. We then examined the results on prostate CT performed one month later. RESULTS: It was necessary to describe transrectal ultrasonic image such as preplanning. There were several cases in which the source arrangement of the schedule was corrected immediately before the operation. In the examination after one month, the numerical value at the start of treatment initially was not satisfactory, but we eventually obtained a result that could to be evaluated. CONCLUSION: We carried out permanent implant brachytherapy for localized prostate cancer using I-125 seeds and reported our experience.     

Radical dose escalation by high-dose-rate brachytherapy for localized prostate cancer—Significance of prostate-specific antigen nadir level within 18 months as correlation for long-term biochemical control

Purpose

High-dose-rate brachytherapy (HDR-BT) for dose escalation in localized prostate cancer has been established as one standard treatment option. However, long-term results at followup (FU) ≥5 years are usually needed to ensure robustness of reported outcomes. Potential benefit of salvage therapy is, nevertheless, higher when relapse is diagnosed early. This study aimed to solve this dilemma by evaluating the prostate-specific antigen (PSA) nadir for early prediction of long-term biochemical control.

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.     

The impact of perineural invasion on biochemical outcome after permanent prostate iodine-125 brachytherapy

PurposePerineural invasion (PNI) in prostate biopsies is associated with increased risk of higher Gleason score and worse pathologic stage. We report the influence of PNI in biochemical no evidence of disease (bNED) survival after ¹²⁵I prostate brachytherapy (BT).Methods and MaterialsPathology reports of 700 men with localized prostate cancer who underwent ¹²⁵I prostate BT in 1999–2008 were reviewed. The presence or absence of PNI in the biopsy was documented in 339 men. Clinical, treatment, and dosimetric parameters, along with PNI status, were evaluated for bNED survival, defined by “nadir + 2” definition.ResultsOf the 339 patients, 87% had favorable risk and 13% intermediate risk. PNI was present in 89 patients (26%). After a median followup of 32 months, there were five biochemical failures (4: +PNI and 1: ?PNI), of which one was local failure (+PNI). Actuarial 5-year bNED survival for the entire group was 97.0% (92.9% for +PNI; 99.2% for ?PNI). In univariate analysis age, pretreatment prostate-specific antigen, Gleason score 7, and intermediate risk group predicted for worse biochemical outcome, whereas the presence of PNI showed a trend toward significance (p = 0.06). Some of the regression algorithms failed to converge because of low event rates.ConclusionsWe report excellent biochemical control in 339 men treated with ¹²⁵I prostate BT. The presence of PNI showed a trend toward significance in predicting 5-year bNED survival but did not impact on local control and should not influence the decision to recommend BT for localized prostate cancer.