Comparison of biochemical failure definitions for permanent prostate brachytherapy

doi:10.1016/j.ijrobp.2006.03.027

International Journal of Radiation OncologyBiologyPhysics

Volume 65, Issue 5, 1 August 2006, Pages 1487-1493

Presented at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), Denver, Colorado, October 18, 2005.

https://doi.org/10.1016/j.ijrobp.2006.03.027 Get rights and content

Purpose: To assess prostate-specific antigen (PSA) failure definitions for patients with Stage T1–T2 prostate cancer treated by permanent prostate brachytherapy.

Methods and Materials: A total of 2,693 patients treated with radioisotopic implant as solitary treatment for T1–T2 prostatic adenocarcinoma were studied. All patients had a pretreatment PSA, were treated at least 5 years before analysis, 1988 to 1998, and did not receive hormonal therapy before recurrence. Multiple PSA failure definitions were tested for their ability to predict clinical failure.

Results: Definitions which determined failure by a certain increment of PSA rise above the lowest PSA level to date (nadir + x ng/mL) were more sensitive and specific than failure definitions based on PSA doubling time or a certain number of PSA rises. The sensitivity and specificity for the nadir + 2 definition were 72% and 83%, vs. 51% and 81% for 3 PSA rises. The surgical type definitions (PSA exceeding an absolute value) could match this sensitivity and specificity but only when failure was defined as exceeding a PSA level in the 1–3 ng/mL range and only when patients were allowed adequate time to nadir. When failure definitions were compared by time varying covariate regression analysis, nadir + 2 ng/mL retained the best fit.

Conclusions: For patients treated by permanent radioisotopic implant for prostate cancer, the definition nadir + 2 ng/mL provides the best surrogate for failure throughout the entire follow-up period, similar to patients treated by external beam radiotherapy. Therefore, the same PSA failure definition could be used for both modalities. For brachytherapy patients with long-term follow-up, at least 6 years, defining failure as exceeding an absolute PSA level in the 0.5 ng/mL range may be reasonable.

Introduction

Recently, there has been considerable interest in revisiting prostate-specific antigen (PSA) failure definitions for external beam radiation therapy. Since the 1996 American Society for Therapeutic Radiology and Oncology (ASTRO) Consensus Conference which established the three PSA rise with backdating definition (1), multiple criticisms of this methodology have been expressed (2, 3, 4), largely because of the availability of data with longer clinical follow-up and the opportunity to apply more sophisticated statistical analysis. Therefore, to reevaluate the ASTRO Consensus definition and explore other definitions, a second Failure Definition Symposium was held in Phoenix in January 2005. In addition to data on external beam radiotherapy patients, included were failure definition analyses for external radiotherapy combined with hormonal therapy and permanent radioisotopic implant. The goal was to establish a uniform failure definition for all radiation modalities, if possible. The information in this study expands on the brachytherapy analysis contributed to the PSA Failure Definition Symposium.

Section snippets

Methods and materials

Eleven institutions combined data on 2693 patients treated with permanent radioisotopic implant, I-125 or Pd-103, as solitary treatment for T1–T2 prostatic adenocarcinoma. Contributing institutions included: M. D. Anderson Cancer Center, New York Prostate Institute, Arizona Oncology Services, Seattle Prostate Institute, Chicago Prostate Institute, Cleveland Clinic, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, Mayo Clinic-Rochester, University of Michigan, and Fox

Results

The median PSA nadir for all brachytherapy patients was 0.25 ng/mL at a median follow-up of 2.36 years. However, PSA nadir was related to the amount of follow-up time after implant such that the median nadir was 0.1 ng/mL for patients with at least 3 years follow-up. In 239 patients who were PSADF at 8 years posttreatment by the nadir + 2 definition, the median nadir PSA was 0.1 ng/mL with a range of 0–2.1 ng/mL. The 75th, 90th, and 95th percentiles were 0.3 ng/mL, 0.5 ng/mL, and 0.8 ng/mL,

Discussion

With the ongoing changes in radiotherapeutic methods and techniques for prostate cancer treatment in conjunction with higher doses and varied fractionation schedules, it is extremely important that a standard methodology to assess efficacy is employed. To compare treatments fairly, a tested and agreed upon PSA failure definition is necessary. While standardizing failure definitions across all treatment modalities for prostate cancer would be ideal, the work reported to date and the analysis

Conclusion

Thorough analysis of biochemical failure definitions for both external beam radiotherapy, with or without hormonal therapy, as well as for brachytherapy for prostatic carcinoma has now been done. The data presented here show that the nadir + 2 definition is the best option for patients with various amounts of follow-up treated by brachytherapy, including for studies with less than 5 years maturity. An absolute definition in the 0.5 ng/mL range could only be applied to brachytherapy patients who

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A Systematic Review on the Role of Imaging in Early Recurrent Prostate Cancer
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In patients treated for prostate cancer, a rising serum prostate-specific antigen (PSA) level is a first sign of relapse, but imaging is needed to determine the localization of the recurrence, which may be local, in lymph nodes, and/or metastatic. With the increasing success rate of earlier salvage therapy, the diagnosis has become pertinent when the recurrent PSA level is still very low.
To systematically review the literature on the role of the existing imaging techniques in patients with early recurrent prostate cancer.
A systematic literature search across the MEDLINE and EMBASE databases was conducted in February 2018, searching for original studies reporting on imaging in a (sub)group of patients with recurrent PSA levels not higher than 5 ng/ml. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The methodological quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool.
A total of 98 studies were included in this systematic review, reporting on the role of transrectal ultrasonography (TRUS), computed tomography (CT), bone scintigraphy (BS), single-photon emission CT, multiparametric magnetic resonance imaging (mpMRI), whole-body MRI (wbMRI), and positron emission tomography (PET)-CT/MRI using 18F fluoro-deoxy-glucose, 11C choline, 18F (fluoro)(methyl)choline, 11C acetate, 18F FACBC (fluciclovine) and prostate-specific membrane antigen (PSMA)-based tracers. CT and BS were not sufficiently sensitive in the early recurrence setting. For the detection of local recurrence, TRUS or mpMRI can be used; however, at the lowest PSA levels, few data were available, only after radical prostatectomy, showing a wide range of positivity. TRUS or mpMRI need to be combined with (PET)-CT to assess distant disease, but new techniques such as wbMRI, PET-MRI, or PET-CT allow for an all-in-one approach. At recurrent PSA levels <0.5 ng/ml, detection rates up to 31.3% were reported using ¹¹C choline PET-CT and up to 65.0% using ⁶⁸Ga PSMA-11 PET-CT. At recurrent PSA levels <0.2 ng/ml, detection rates of ⁶⁸Ga PSMA-11 PET-CT ranged from 11.3% to as high as 58.3%.
Detection rates of different imaging techniques depend on the PSA level at the time of imaging. Recent advanced imaging techniques may detect the localization of the recurrence, even when the PSA levels are still very low.
In patients treated for prostate cancer, a rising serum prostate-specific antigen (PSA) level is a sign of recurrence of the disease. Advanced imaging techniques may demonstrate the localization of the recurrence, even when the PSA levels are still very low.
Low-dose-rate prostate brachytherapy: 4–8 week postimplant prostate-specific antigen a novel predictor of biochemical failure-free survival
2017, Brachytherapy
The purpose of this study was to determine the relationship between patient, disease, and treatment variables and biochemical failure-free survival (bFFS) following low-dose-rate prostate brachytherapy (LDR-BT).
Data from 624 consecutive patients who received LDR-BT for localized prostate cancer between 2002 and 2012 at a single institution were collected for various patient, disease, and treatment characteristics including a 4–8 week postimplant PSA (4–8wkPSA). Subgroup analysis was stratified by risk category and treatment regimen. Analysis was performed using Kaplan–Meier survival curves, Cox proportional hazard ratios (HRs), and receiver-operator characteristic curves.
A total of 624 consecutive patients were included with followup time of 4.0 ± 3.1 years. Predictors of bFFS included PSA nadir and 4–8wkPSA (HR = 2.48, p = 0.000 and HR = 1.24, p = 0.000, respectively) for total population. Diabetes mellitus (p = 0.026), chronic obstructive pulmonary disease (p = 0.000), alcohol use (p = 0.024), and age (p = 0.002) were predictors for specific subgroups. Receiver-operator characteristic curves 4–8wkPSA were found to be significant (p = 0.036).
4–8wkPSA is a novel predictor of bFFS for patients receiving LDR-BT across several risk categories and treatment regimens with potential clinical utility as a prognostic indicator. Certain comorbidities and exposure histories also demonstrated significant relationships with bFFS including chronic obstructive pulmonary disease, diabetes mellitus, age, alcohol history, proton pump inhibitor use, PSA nadir, and PSA density.
Oncological and functional results of robotic salvage radical prostatectomy after permanent brachytherapy implants
2017, Cancer/Radiotherapie
To evaluate the feasibility of robotic salvage prostatectomy for local recurrence after permanent brachytherapy implants for prostate cancer.
Seven patients were operated by robotic salvage prostatectomy with or without pelvic lymph node dissection between October 2007 and March 2012, for a local recurrence after iodine 125 permanent brachytherapy implants. Local recurrence was proved by prostate biopsies, once biochemical relapse was diagnosed and imaging assessment performed.
The average age of a patient at the time of diagnosis was 66 years (62–71 years). The median nadir prostate specific antigen (PSA) serum concentration after brachytherapy was 1.29 ng/mL (0.6–2.1 ng/mL), obtained after a median of 12 months (7–21 months). The average [PSA] before robotic salvage prostatectomy was 6.60 ng/mL (4.17–13.80 ng/mL). [PSA] at 1 and 3 months after prostatectomy was less than 0.05 ng/mL in five patients. [PSA] remained below 0.05 ng/mL for six patients at 12 and 24 months. One month after robotic salvage prostatectomy, all patients had at least partial urinary incontinence. At 12 and 24 months after robotic salvage prostatectomy four patients have regained full urinary continence. In terms of erectile function at 24 months, three patients retained erectile function with possible sexual intercourse.
Robotic salvage prostatectomy appears to be a reliable treatment in terms of oncological outcome with convincing results both for urinary continence and erectile function for selected patients with local recurrence after permanent brachytherapy implants.
Évaluer la faisabilité d’une prostatectomie de rattrapage robotisée pour une rechute locale après une curiethérapie de prostate initiale par implants permanents.
D’octobre 2007 à mars 2012, sept patients pris initialement en charge par curiethérapie de prostate par iode 125, en situation de rechute locale, ont bénéficié d’une prostatectomie robotisée avec ou sans curage pelvien ganglionnaire. Les patients étaient en situation de rechute biologique selon la concentration sérique de d’antigène spécifique de la prostate et avaient eu un bilan d’imagerie complet. Le diagnostic de rechute locale a été confirmé par les biopsies prostatiques.
L’âge moyen des patients au moment du diagnostic était de 66 ans (62–71). Le nadir médian de la concentration sérique de d’antigène spécifique de la prostate à un an de la curiethérapie était de 1,29 ng/mL (0,6–2,1 mg/mL). La concentration moyenne d’antigène spécifique de la prostate lors du traitement de rattrapage par prostatectomie robotisée était de 6,60 ng/mL (4,17–13,80 ng/mL). La concentration sérique de d’antigène spécifique de la prostate était à 1 et 3 mois de la prostatectomie de moins de 0,05 ng/mL pour cinq patients. À 12 et 24 mois, elle est restée inférieure à 0,05 ng/mL pour six patients. Un mois après la chirurgie, tous les patients souffraient d’une incontinence urinaire partielle. À 12 et 24 mois, cinq patients avaient une continence parfaite. Pour ce qui concerne la fonction érectile, à 24 mois, trois patients ont conservé une fonction érectile permettant les rapports.
La prostatectomie de rattrapage robotisée réalisée pour des patients sélectionnés en situation de rechute locale après curiethérapie est une option thérapeutique à considérer, avec des résultats fiables et des résultats fonctionnels probants en termes de continence et de conservation érectile.

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¹: D.A. Kuban was supported by an Educational Grant from Oncura.

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Clinical investigationProstateComparison of biochemical failure definitions for permanent prostate brachytherapy

Introduction

Section snippets

Methods and materials

Results

Discussion

Conclusion

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

J Urol

J Urol

J Urol

J Urol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clinical investigation
Prostate
Comparison of biochemical failure definitions for permanent prostate brachytherapy