Long-Term Biochemical and Survival Outcome of 921 Patients Treated With I-125 Permanent Prostate Brachytherapy

doi:10.1016/j.ijrobp.2009.03.049

International Journal of Radiation OncologyBiologyPhysics

Volume 76, Issue 5, April 2010, Pages 1433-1438

https://doi.org/10.1016/j.ijrobp.2009.03.049 Get rights and content

Purpose

To assess long-term biochemical and survival outcome after permanent prostate brachytherapy (BT).

Methods and Materials

Data on 921 patients, treated with permanent interstitial BT monotherapy between 1989 and 2004 for ≤T2c Nx/0 Mx/0 prostate cancer were evaluated. All patients were treated with I-125 seeds (prescription dose 144 Gy). Eighty-five patients with a gland volume ≥50cc received 6 months of antiandrogen therapy before treatment. Patients were classified into risk groups with 232 defined as low-, 369 intermediate-, and 320 high-risk disease. The median follow-up was 69 months (range, 4–186 months); mean age was 67 years.

Results

Average 5- and 10-year biochemical no evidence of disease (bNED) rates were 79% and 57%. Average 10-year bNED rates by risk group were 88% for low-risk, 61% for intermediate-risk, and 30% for high-risk disease. The average 10-year overall and disease-specific survival rates were 59% and 82%. Ten-year overall and disease-specific survival rates by risk group were, respectively, 68% and 96% for low-risk, and 64% 87% for intermediate-risk, and 49% and 69% for high-risk disease. In multivariate Cox regression analysis, both risk group and treatment era were independent predictors of bNED and survival.

Conclusions

These data on long-term survival continue to support the use of I-125 monotherapy for prostate cancer in low-risk patients and, in particular, demonstrate its efficacy in intermediate-risk patients.

Introduction

Adenocarcinoma of the prostate is the number-one male cancer in both the United States and Europe. As prostate cancer awareness increases, so does its screening, which in particular results in an increase of early-stage, localized disease.

For patients with favorable tumor characteristics, i.e., well-differentiated tumors with a low initial prostate specific antigen (IPSA) level and low tumor stage, treatment outcome with prostate brachytherapy (PB) generally is considered excellent 1, 2. International guidelines do not suggest the use of PB for intermediate- and high-risk patients, for whom it is considered less effective 3, 4, 5. However the evidence for these recommendations is limited and needs to be further established. In particular, long-term follow-up is lacking because of the long natural course of prostate cancer. Thus, only few studies have reported reasonably long-term follow-up for patients treated with brachytherapy. Unfortunately, most of these studies had a follow-up of less than 10 years, used different biochemical recurrence and risk group definitions, reported only a small number of patients, or used additional treatment such as external radiotherapy 6, 7, 8, 9, 10, 11, 12, 13. Because of the long natural history of prostate cancer, outcome is mostly reported as biochemical recurrence (BCR), which is considered the best surrogate outcome measure for disease-specific survival (DSS) (14). We report long-term outcome regarding BCR, overall survival (OS), and DSS for 921 patients with monotherapeutic permanent I-125 PB.

Section snippets

Methods and Materials

Between January 1989 and October 2004, 945 patients with biopsy-proven adenocarcinoma of the prostate were treated with permanent interstitial I-125 PB using a transrectal ultrasound-guided approach. The patient characteristics are shown in Table 1. Patients were considered for brachytherapy if the tumor stage was T≤2c, tumor grade <3 (Gleason <8), Nx/0, and Mx/0, although patients with a large transurethral prostatectomy (TURP) cavity were excluded from therapy. Patients without data regarding

Results

Table 2 shows treatment outcome of time both until BCR and death, as well as estimates for bNED and survival. There was a highly significant difference in median months until BCR between low-, intermediate-, and high-risk patients with higher risk associated with shorter time to failure. The number of men dying from prostate cancer in the low- (n = 5) and intermediate-risk groups (n = 8) was too small for valid comparison, but the same trend for higher risk and shorter time to death was seen as

Discussion

This article reports long-term bNED and survival outcomes after I-125 PB from a single institution and includes 921 patients who received I-125 PB as monotherapy, resulting in extensive follow-up in terms of both time and sample size. Low- and intermediate-risk patients showed excellent bNED and DSS. Age-adjusted life expectancy for healthy control subjects is equal to our low- and intermediate-risk PB patients (21). This effectively means that prostate cancer seems to have no effect on overall

Conclusion

In this article, we compared the long-term follow-up data for PB patients from our institution with available literature. We confirm the positive effect on clinical outcome of PB in low-risk prostate cancer patients and also demonstrate this effect in intermediate-risk patients. We suggest revision of guidelines and nomograms to include intermediate-risk patients as suitable candidates for PB monotherapy. For high-risk disease, further evaluation is necessary, and the use of concurrent EBRT

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Cited by (108)

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
2021, Brachytherapy
To 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.
Men 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.
A 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.
HDRB 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.
Ultra-long-term toxicity of prostate brachytherapy
2021, Brachytherapy
The true long-term toxicity associated with most radiation treatments is unknown. Prostate cancer patients survive decades after prostate cancer brachytherapy, with unclear long-term toxicity profiles. We therefore evaluated prostate cancer patients who had received I-125 brachytherapy treatment (14,400 cGy) 14–24 years prior and assessed their long-term quality of life based on urinary, bowel, and sexual function.
We performed a single-institutional, retrospective analysis of 39 men who received brachytherapy between 1996 and 2005. Analysis was based on physician evaluations, laboratory values, and International Prostate Symptom Score (IPSS) results.
At last followup, the mean patient age was 80 years (median 81 years), with a mean of 17.8 years posttreatment followup. Fifteen percent of patients had experienced recurrence. Urinary symptoms were limited, with 0% of patients reporting dysuria, 13% reporting incontinence, and 33% on medication for urinary symptoms. Average times nocturia was 1.7 with mean IPSS of 6.4. With regard to bowel symptoms, 3% of patients reported incontinence, 8% noted diarrhea, 3% had rectal bleeding, 8% noted constipation, and no patients required prescription medication for bowel function. Thirty-nine percent of patients potent before treatment reported being potent with or without medication.
Prostate cancer survivors, postbrachytherapy treatment, have an overall good quality of life for many years to come. Urinary and bowel symptoms are limited, IPSS scores are generally low, and patients who consider sexual function important at their stage in life are frequently found to be potent. Overall, the long-term side effects of brachytherapy are limited at 14–24 years posttreatment.
Diagnostic performance of imaging techniques for detecting of local recurrence after prostate brachytherapy
2020, Cancer/Radiotherapie
The purpose of this study was to evaluate MRI and fluorocholine PET/CT diagnostic performances for the detection of local recurrence following prostate brachytherapy for localised prostate cancer.
In this single-centre study, we retrospectively reviewed data from 21 patients treated by brachytherapy for localised prostate cancer and diagnosed with biochemical recurrence according to Phoenix Criteria, who underwent MRI and fluorocholine PET/CT. We included patients with local relapse suspicion according to imaging exams, with biopsy for the final assessment of local recurrence. Patient analysis data were supplemented by segment analysis using an 8-segment model.
The fluorocholine PET/CT was positive for 81% and negative for 19% of patients. The sensitivity and specificity were 92% and 33% with diagnosis accuracy of 67%. The MRI was positive for 57% and negative for 43% of patients. The sensitivity and specificity were 67% and 56% with diagnosis accuracy of 62%. There was no statistically significant difference between fluorocholine PET/CT and MRI accuracy (P = 0.63). On a segment-based analysis, the sensitivity and specificity were 44% and 82% for fluorocholine PET/CT with diagnosis accuracy of 78%. For MRI, specificity was 91% diagnosis accuracy was 82%.
Both MRI and fluorocholine PET/CT permit to highlight local recurrence sites after prostate brachytherapy. Confirmation biopsies are, however, necessary since this accuracy is insufficient.
L’objectif de ce travail était d’évaluer les performances de la tomographie par émission de positons (TEP)–scanographie à la (¹⁸F)-fluorocholine ou l’IRM en cas de rechute biochimique après curiethérapie d’un cancer de la prostate localisé, qui sont peu décrites dans la littérature.
Il s’agit d’une étude monocentrique rétrospective incluant 21 patients pris en charge par curiethérapie pour un cancer de la prostate localisé en rechute biochimique selon les critères de Phoenix. Tous les patients ont eu une IRM et une TEP–scanographie à la (¹⁸F)-fluorocholine. Nous avons inclus les patients avec une suspicion de la rechute locale selon l’imagerie et pour qui une biopsie confirmait le diagnostic d’adénocarcinome de prostate. Un modèle d’analyse par patient et par segment a été utilisé.
La TEP–scanographie à la (¹⁸F)-fluorocholine était positive chez 81% des patients, négative chez 19%. La sensibilité et la spécificité étaient de 92% et 33%. L’IRM était positive pour 57% des patients, avec respectivement une sensibilité et une spécificité de 67% et 56%. Aucune différence significative n’a été retrouvée entre les deux méthodes d’imagerie pour la détection (p = 0,63). En analyse par segment, la sensibilité était de 44% et la spécificité était de 82% pour la TEP–scanographie à la (¹⁸F)-fluorocholine. Pour l’IRM, la spécificité était de 91%.
L’IRM ou la TEP–scanographie à la (¹⁸F)-fluorocholine permet de mettre en évidence une rechute locale après curiethérapie d’un cancer de la prostate localisé. Cependant, les biopsies de confirmation sont nécessaires du fait des limites de ces deux imageries en termes de détection.
Changes in lower urinary tract symptoms after iodine-125 brachytherapy for prostate cancer
2019, Clinical and Translational Radiation Oncology
To investigate chronological changes in lower urinary tract symptoms (LUTS) in patients who received iodine-125 brachytherapy (BT) for prostate cancer.
We enrolled 706 patients who received BT. Of these, 265 (38%) received BT combined with external beam radiation therapy (EBRT). An International Prostate Symptom Score (IPSS), IPSS quality of life (IPSS-QOL) score, and overactive bladder symptom score (OABSS) were recorded before BT (baseline, BL), and 1, 3, 6, 12, 24, 36, 48, and 60 months after BT. The sum of frequency (2), urgency (4) and nocturia (7) of the IPSS questionnaire was defined as the storage symptoms score, whereas the sum of emptying (1), intermittency (3), weak stream (5), and hesitancy (6) was defined as the voiding symptom score.
Total IPSS significantly increased at 3 months following BT compared with BL (mean score: 17.1 vs. 7.99, P < 0.001) and returned to BL by 36 months. The storage symptom score did not return to BL 36 months after BT. Total OABSS significantly increased 3 months after BT compared with BL (mean score: 6.52 vs. 3.45, P < 0.001), and returned to BL 48 months after BT. The IPSS-QOL score was the highest score (mean score: 2.46 vs. 3.9, P < 0.001) 3 months after BT and returned to BL 48 months after BT, however the IPSS-QOL score was lower than BL (mean score: 2.01 vs 2.46, P < 0.001) at 60 months. The risk factors for LUTS within 1 year after BT were BL IPSS (P < 0.001) and PV (P < 0.001). Patients who received combined EBRT experienced transient storage symptoms 24 and 36 months after BT, whereas those who received BT alone did not. However, the storage symptom score of the patients who received combined EBRT was improving 48 months after BT and eventually showed no significant difference compared with those treated with BT alone.
Three months after BT, LUTS, including storage symptoms, deteriorated the most but improved with time. The urinary symptom in patients who received combined EBRT can potentially flare again in 24 and 36 months after BT. Knowledge of changes in LUTS associated with BT may influence treatment recommendations and enable patients to make better-informed decisions.
Multicenter Evaluation of Biochemical Relapse–Free Survival Outcomes for Intraoperatively Planned Prostate Brachytherapy Using an Automated Delivery System
2017, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
This gives oncologists the ability to add extra seeds in areas of suboptimal dosimetry, which is impossible to evaluate and correct with the preplanning technique. Despite these potential benefits from intraoperative brachytherapy, to date, aside from a few exceptions, most long-term published outcomes used preplanned prostate brachytherapy techniques (7, 8). In contrast with our long experience with the intraoperative technology and excellent single-institution published outcomes (5), one intraoperative study describes better outcomes using the Mick applicator (Mick Radio-Nuclear Instruments, Mount Vernon, NY) compared with the automated FIRST/seedSelectron system (Elekta Brachytherapy, Stockholm, Sweden) (8, 9).
To report biochemical recurrence in prostate cancer treated with intraoperatively planned low-dose-rate prostate brachytherapy using an automated delivery system (IO-LDRB).
Between 2003 and 2013, 2608 patients from 3 centers were treated with IO-LDRB as single-modality treatment for low or low-tier intermediate-risk prostate cancer. Databases from the 3 centers have been analyzed. These independent databases were collected prospectively. Patient, tumor, and treatment characteristics were then compared, Kaplan-Meier survival estimates of biochemical relapse–free survival (bRFS) were generated, and the Cox proportional hazards model was used to determine factors predicting for relapse.
A total of 2608 patients with a median follow-up of 4.7 (interquartile range, 3.1-6.9) years were analyzed. Median age was 64 (range, 42-84) years. In these patients, median initial prostate-specific antigen was 5.5 ng/mL, 74% were T1, and 26% were T2; 73% were Gleason 6, and 25% Gleason 7. Median percentage of biopsy cores positive was 33%, and median gland volume was 34.2 cm³. Eleven percent of patients received hormones for a median of 3.0 months before implantation. Median seed activity was 0.437 mCi, D90 (dose covering 90% of the prostate volume) was 186.7 Gy, and V100 was 99.37%. Biochemical relapse was observed in 124 patients (4.8%), and median time to failure was 4.0 years. Predicted bRFS was 93% at 7 years. On Cox regression bRFS was dependent only on D90 at the time of implantation and prostate-specific antigen density.
This study demonstrates that IO-LDRB is an effective treatment option for patients with low and low-tier intermediate-risk prostate cancer. Rates of biochemical relapse remain low several years after treatment. These results compared favorably to published manual preplan technique results.
Low-dose-rate Brachytherapy for Prostate Cancer in Low-resource Settings
2017, International Journal of Radiation Oncology Biology Physics
In areas with limited health care, it is important to identify and implement effective treatment methods and to optimize available resources. We investigated the implementation of a low-dose-rate (LDR) brachytherapy program for the treatment of prostate cancer (PCa) in a low-resource setting such as Puerto Rico (PR), where PCa is the main cause of cancer-associated death.
After institutional approval, the medical records of patients with nonmetastatic PCa undergoing LDR brachytherapy from 2008 to 2013 were reviewed from PR. The factors analyzed included adequate D₉₀ (radiation dose delivered to 90% of the target volume) coverage (≥140 Gy), early and late toxicity (Common Terminology Criteria for Adverse Events grade >2), and prostate-specific antigen failure. Freedom from biochemical failure was evaluated using Kaplan-Meier analysis.
The barriers to implementation of LDR brachytherapy in a country with limited resources were identified. These included lack of access to funding for startup costs, specific referral patterns, lack of trained support staff, such as dosimetrists and physicists, and initial opposition from insurance companies for reimbursement. The initial results from 191 patients were included in the present study with a median follow-up period of 26 months. Prostate-specific antigen failure occurred in 6 patients (3%). No early or late gastrointestinal toxicity (grade >2) developed. Only 3 (2%) and 2 (1%) patients experienced early and late genitourinary toxicity (grade >2), respectively. The 2- and 3-year freedom from biochemical failure in this population was 97% and 95.9%, respectively.
At present, limited data are available delineating the barriers faced by low-resource settings in the implementation of LDR brachytherapy. Our data highlight the issues unique to this environment and support the use of LDR brachytherapy as a reliable and effective treatment modality for patients with PCa in low-resource settings.

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Clinical InvestigationLong-Term Biochemical and Survival Outcome of 921 Patients Treated With I-125 Permanent Prostate Brachytherapy

Purpose

Methods and Materials

Results

Conclusions

Introduction

Section snippets

Methods and Materials

Results

Discussion

Conclusion

Int J Radiat Oncol Biol Phys

Eur Urol

Int J Radiat Oncol Biol Phys

Brachytherapy

J Urol

Int J Radiat Oncol Biol Phys

J Urol

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Lancet Oncol

Clinical Investigation
Long-Term Biochemical and Survival Outcome of 921 Patients Treated With I-125 Permanent Prostate Brachytherapy