Predicting biochemical tumor control after brachytherapy for clinically localized prostate cancer: The Memorial Sloan-Kettering Cancer Center experience

PurposeTo identify predictors of biochemical tumor control and present an updated prognostic nomogram for patients with clinically localized prostate cancer treated with brachytherapy.Methods and MaterialsOne thousand four hundred sixty-six patients with clinically localized prostate cancer were treated with brachytherapy alone or along with supplemental conformal radiotherapy. Nine hundred one patients (61%) were treated with Iodine-125 (¹²⁵I) monotherapy to a prescribed dose of 144 Gy, and 41 (4.5%) were treated with Palladium-103 (¹⁰³Pd) monotherapy to a prescribed dose of 125 Gy. In patients with higher risk features (n = 715), a combined modality approach was used, which comprised ¹²⁵I or ¹⁰³Pd seed implantation or Iridium-192 high–dose rate brachytherapy followed 1–2 months later by supplemental intensity-modulated image-guided radiotherapy to the prostate.ResultsThe 5-year prostate-specific antigen relapse-free survival (PSA-RFS) outcomes for favorable-, intermediate-, and high-risk patients were 98%, 95%, and 80%, respectively (p < 0.001). Multivariate Cox regression analysis identified Gleason score (p < 0.001) and pretreatment PSA (p = 0.04) as predictors for PSA tumor control. In this cohort of patients, the use of neoadjuvant and concurrent androgen deprivation therapy did not influence biochemical tumor control outcomes. In the subset of patients treated with ¹²⁵I monotherapy, D₉₀ > 140 Gy compared with lower doses was associated with improved PSA-RFS. A nomogram predicting PSA-RFS was developed based on these predictors and had a concordance index of 0.70.ConclusionsResults with brachytherapy for all treatment groups were excellent. D₉₀ higher than 140 Gy was associated with improved biochemical tumor control compared with lower doses. Androgen deprivation therapy use did not impact on tumor control outcomes in these patients.     

Late,persistent, substantial treatment-related symptoms (LAPERS) following low-dose-rate brachytherapy for prostate cancer

PurposeWe aim to report 1) prevalence, 2) incidence, and 3) late, persistent, substantial treatment-related symptoms (LAPERS) after low-dose-rate brachytherapy (LDRBT) for prostate cancer.Methods and materialsThe study comprised men treated with LDRBT in a single Australian institution between 2014 and 2019. All men completed the Expanded Prostate Cancer Index Composite 26 (EPIC-26) questionnaire pretreatment, and at regular intervals posttreatment. ‘Substantial’ symptoms were defined as ‘moderate’ or ‘big’ problems in EPIC-26 which assesses the degree of symptom bother for each functional domain. ‘Persistent’ symptoms were defined as ‘substantial’ symptoms that present in at least half of the ‘late’ followup assessments. This provided a binary LAPERS outcome (yes/no). Prevalence (at each time point) and cumulative incidence of substantial symptoms were also reported.ResultsA total of 172 men with ‘baseline’ and at least three ‘late’ followup EPIC-26 were included in the study. The median followup was 60 months (IQR: 36–74 months). For overall urinary function, prevalence of substantial symptoms was highest at 10% 6-month posttreatment, with 5-year cumulative incidence of 18%, but only 2% had LAPERS. For overall bowel function, prevalence of substantial symptoms was highest at 7% 12-months posttreatment, with 5-year cumulative incidence of 15%, and only 2% had LAPERS. For sexual function, prevalence of substantial symptoms was highest at 28% 6-months posttreatment, with 5-year cumulative incidence of 49%, and 22% had LAPERS (baseline-adjusted LAPERS 17%).ConclusionsThere were considerable differences in late toxicities using different toxicity-reporting approaches. LAPERS approach is more reflective of ‘true’ late toxicities considering duration and persistence of symptoms.     

Detection of failure patterns using advanced imaging in patients with biochemical recurrence following low-dose-rate brachytherapy for prostate cancer

PURPOSE/OBJECTIVE(S)This study describes the pattern of failure in patients with biochemical (BCR) recurrence after low-dose-rate (LDR) brachytherapy as a component of definitive treatment for prostate cancer.METHODSPatients with BCR after LDR brachytherapy ± external beam radiation therapy (EBRT) were enrolled on prospective IRB approved advanced imaging protocols. Patients underwent 3T multiparametric MRI (mpMRI); a subset underwent prostate specific membrane antigen (PSMA)-based PET/CT. Pathologic confirmation was obtained unless contraindicated.RESULTSBetween January 2011 and April 2021, 51 patients with BCR after brachytherapy (n = 36) or brachytherapy + EBRT (n = 15) underwent mpMRI and were included in this analysis. Of 38 patients with available dosimetry, only two had D90<90%. The prostate and seminal vesicles were a site of failure in 66.7% (n = 34) and 39.2% (n = 20), respectively. PET/CT (n = 32 patients) more often identified lesions pelvic lymph nodes (50%; n = 16) and distant metastases (18.8%; n = 6), than mpMRI. Isolated nodal disease (9.8%; n = 5) and distant metastases (n = 1) without local recurrence were uncommon. Recurrence within the prostate was located in the transition zone in 48.5%, central or midline in 45.5%, and anterior in 36.4% of patients.CONCLUSIONIn this cohort of patients with BCR after LDR brachytherapy ± EBRT, the predominant recurrence pattern was local (prostate ± seminal vesicles) with frequent occurrence in the anterior prostate and transition zone. mpMRI and PSMA PET/CT provided complementary information to localize sites of recurrence, with PSMA PET/CT often confirming mpMRI findings and identifying occult nodal or distant metastases.     

Radiation protection and dosimetry issues for patients with prostate cancer after I-125 low-dose-rate brachytherapy permanent implant

PurposeThe aim of this work was to analyze the exposure rates measured in the proximity of patients who underwent prostate low-dose-rate brachytherapy with I-125 implant. Effective doses to relatives and to population were computed to estimate the time to reach radioprotection dose constraints.Methods and MaterialsMeasurements were obtained from 180 patients, whereas the body mass index was calculated and reported for 77 patients. The day after the implant, $\dot{K}$ measurements were conducted at various skin distances and positions and converted to effective doses. A theoretical model was developed to estimate effective doses from total implanted activity. The latter was approximated with a 10-mL vial inside the patient.ResultsThe $\dot{K}$ measurements showed a low correlation with the total implanted activity, albeit an increasing trend of $\dot{K}$ was observed on increasing the activity. A stronger correlation was found between body mass index and $\dot{K}$ measurements.The effective dose to population is in general lower than dose constraints as well as the effective doses to relatives, with the exception of children and pregnant women, who command special precautions. We report differences between the experimental model– and theoretical model–based dose evaluation together with their comparison with previous studies found in literature.ConclusionsBased on the $\dot{K}$ measurements and the results of the present analysis, it is possible to provide the patient with radiation safety instructions specifically tailored to his relatives’ habits and working environment.     

Dose distribution and morbidity after high dose rate brachytherapy for prostate cancer: influence of V150 and V200 parameters

The purpose of this study is to identify factors predicting morbidity in patients undergoing high dose rate (HDR) brachytherapy boost with external beam irradiation for prostate cancer. Acute and late morbidity data were collected for 104 prostate cancer patients treated with an HDR boost together with external beam radiotherapy. Significant urinary and rectal morbidity were correlated with urethral and rectal point doses, and the proportions of the target volume receiving 100%, 150% and 200% (V200) or more of the prescribed dose. Rectal or urethral point doses did not predict morbidity. By contrast, the V200 was significantly higher for patients experiencing either acute or late urinary morbidity. The cut-off V200 was 15% of the target volume. Although theoretically beneficial for tumour cell kill, the treatment of significant proportions of the prostate to high dose might be associated with increased morbidity, and should preferably be avoided.     

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.     

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.

Use of a rectal spacer with low-dose-rate brachytherapy for treatment of prostate cancer in previously irradiated patients: Initial experience and short-term results

BackgroundSalvage brachytherapy in patients with prior pelvic radiation carries a risk of rectal injury. Herein, we report our initial experience using a hydrogel spacer between the prostate and the rectum during salvage brachytherapy.Methods and MaterialsA total of 11 patients with prostate cancer and prior radiotherapy (5 prostate brachytherapy, 2 prostate external beam radiation therapy [EBRT], and 4 rectal cancer EBRT) received ¹²⁵I brachytherapy after attempted placement of 10 cc of a diluted hydrogel spacer between the prostate and rectum.ResultsSpacing was achieved in 8 of the 11 (73%) patients but was not possible in 3 (1 prior brachytherapy and 2 prior EBRT) owing to fibrosis and adhesions. For the 8 patients in whom spacing was accomplished, the median space between the prostate and rectum was 10.9 mm (prior EBRT) vs. 7.7 mm (prior brachytherapy), p = 0.048. Median followup was 15.7 months. One patient developed a prostato-rectal fistula requiring a diverting colostomy. The 16-month estimate of late Grade 3 or 4 gastrointestinal or genitourinary toxicity was 26%. One patient developed lymph node–positive recurrence. The 16-month prostate-specific antigen failure-free survival rate was 89%. Compared with baseline, Expanded Prostate Cancer Index Composite for Clinical Practice urinary quality of life (QoL) was significantly worse at 3 and 6 months but not significantly worse by 1 year. There were no significant changes throughout the study period in bowel or sexual QoL.ConclusionHydrogel spacer placements may be feasible in most patients with prior pelvic radiation. Further followup is needed to determine whether spacer placement will produce long-term improvements in toxicity or QoL.     

The concept of erectile function preservation (penile rehabilitation) in the patient after brachytherapy for prostate cancer

PurposeRadiation therapy (RT) for prostate cancer is commonly associated with erectile dysfunction (ED), although high-quality data on incidence of ED after brachytherapy (BT) are limited. We reviewed the literature on BT-related ED and propose a clinical pathway for maximal preservation of erectile function (EF) after treatment.Methods and MaterialsErectile physiology and pathophysiology after RT are reviewed. Evidence and rationale for the concept of penile rehabilitation are presented. BT literature that focuses on ED is identified. A clinical care pathway for maximally preserving EF in patients treated with RT for localized prostate cancer is proposed.ResultsThe mechanisms contributing to ED after prostate irradiation involve injury to the neurovascular bundles, penile vasculature, and cavernosal structural tissue. Reported rates of ED after BT vary widely. Basic science and clinical studies support the concept of a structured program of erectile tissue preservation for optimizing EF after radical prostatectomy and are adapted for the prostate radiation patient.ConclusionsAlthough definitive evidence for such erectile tissue preservation strategies is pending, there is a solid scientific rationale for the application of available strategies to the radiation patient.     

In vivo dosimetry with semiconductors in medium dose rate (MDR) brachytherapy for cervical cancer

Purpose

This study was performed to evaluate the role of in vivo dosimetry with semiconductor detectors in gynaecological medium dose rate brachytherapy, and to compare the actual doses delivered to organs at risk (as measured using in vivo dosimetry) with those calculated during treatment planning.

Materials and methods

Doses to the rectum and bladder were measured in a group of patients with cervical carcinoma using semiconductor detectors and compared to the doses calculated using a treatment planning system. 36 applications of brachytherapy at dose rates of 1.8–2.3 Gy/h were performed in the patients.

Results

The mean differences between the measured and calculated doses were 3 % for the rectum and 11 % for the bladder.

Conclusions

The main reason for the differences between the measured and calculated doses was patient movement. To reduce the risk of large errors in the dose delivered, in vivo dosimetry should be performed in addition to treatment planning system computations.     

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.     

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.     

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.