Postoperative Nomogram Predicting the 9-Year Probability of Prostate Cancer Recurrence After Permanent Prostate Brachytherapy Using Radiation Dose as a Prognostic Variable

doi:10.1016/j.ijrobp.2009.03.031

International Journal of Radiation OncologyBiologyPhysics

Volume 76, Issue 4, 15 March 2010, Pages 1061-1065

Presented orally at the 49th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, October 28–November 1, 2007, Los Angles, CA.

https://doi.org/10.1016/j.ijrobp.2009.03.031 Get rights and content

Purpose

To report a multi-institutional outcomes study on permanent prostate brachytherapy (PPB) to 9 years that includes postimplant dosimetry, to develop a postimplant nomogram predicting biochemical freedom from recurrence.

Methods and Materials

Cox regression analysis was used to model the clinical information for 5,931 patients who underwent PPB for clinically localized prostate cancer from six centers. The model was validated against the dataset using bootstrapping. Disease progression was determined using the Phoenix definition. The biological equivalent dose was calculated from the minimum dose to 90% of the prostate volume (D90) and external-beam radiotherapy dose using an α/β of 2.

Results

The 9-year biochemical freedom from recurrence probability for the modeling set was 77% (95% confidence interval, 73–81%). In the model, prostate-specific antigen, Gleason sum, isotope, external beam radiation, year of treatment, and D90 were associated with recurrence (each p < 0.05), whereas clinical stage was not. The concordance index of the model was 0.710.

Conclusion

A predictive model for a postimplant nomogram for prostate cancer recurrence at 9-years after PPB has been developed and validated from a large multi-institutional database. This study also demonstrates the significance of implant dosimetry for predicting outcome. Unique to predictive models, these nomograms may be used a priori to calculate a D90 that likely achieves a desired outcome with further validation. Thus, a personalized dose prescription can potentially be calculated for each patient.

Introduction

Accurate prediction models for prostate cancer recurrence after permanent prostate brachytherapy (PPB) are valuable for patient counseling and for considering the role of adjuvant therapies. Numerous prognostic variables associated with disease recurrence after PPB have been identified, including serum prostate-specific antigen (PSA) level, Gleason grade, and pathologic stage. In 2001, a PPB nomogram was developed on the basis of a three-center cohort of 3,512 patients that calculated a man's 5-year biochemical freedom from recurrence (BFFF) after PPB and included external beam radiotherapy (EBRT) as an independent variable (1).

In 1999, the American Brachytherapy Society provided a consensus statement regarding PPB and included the recommendation that all patients treated by PPB should undergo postimplant dosimetry for purposes of quality assurance (2). Such postimplant dosimetry is usually performed by computed tomography conducted within 30 days of the procedure. The Radiation Therapy Oncology Group has completed two Phase I/II clinical trials involving PPB requiring such CT-based postimplant dosimetry 3, 4. Furthermore, in 1998 Stock et al.(5) published data demonstrating that there exists a dose–response relationship for ¹²⁵I brachytherapy, such that patients who receive a higher dose to the prostate are less apt to suffer biochemical failure (5). An update of this series and other have supported this dose–response relationship 6, 7. In this report we update the original PPB nomogram with one that includes results of postimplant dosimetry as well as other potential prognostic factors. This study uses a larger multi-institutional patient cohort to develop a postoperative nomogram predicting BFFF to 9 years that uses postimplant dosimetry as an independent variable. Furthermore, this nomogram now predicts recurrence on the basis of the Phoenix definition.

Section snippets

Methods and Materials

Six treatment centers, the North Shore Long Island Jewish Health System, Mt. Sinai Medical Center, Cleveland Clinic Foundation, Mayo Clinic, Memorial Sloan-Kettering Cancer Center, and University of California at San Francisco supplied clinical and raw follow-up data on 5,931 consecutively treated PPB patients. All six centers obtained institutional review board approval to share their raw patient data, which was entered into Prostate Research Database (Fearn and Potters, NY), an Access-based

Results

The pretreatment patient characteristics of all patients are summarized in Table 1. The median follow-up was calculated by censored events, not lifetime visits, and was 43.6 months (range, 0–160 months). The mean number of follow-up PSA values per patient was 5.3 (range, 1–28). Median pretreatment PSA level was 6.8 ng/mL (range, 0–120 ng/mL). The 9-year BFFF probability was 77% (Fig. 1). Prostate-specific antigen, clinical stage, Gleason sum, isotope, year of treatment, EBRT, and prostate D90

Discussion

Kattan et al.(1) have previously reported on the merits of a continuous multivariable pretreatment prostate brachytherapy nomogram for prostate cancer recurrence after PPB. Although the nomogram is considerably more complicated to use than the National Comprehensive Cancer Network risk-grouping schemata, the added complexity of nomograms results in enhanced predictive accuracy. Furthermore, the nomogram predictions are tailored to the risk posed by the characteristics of an individual's cancer,

References (9)

M.W. Kattan et al.
Pretreatment nomogram for predicting freedom from recurrence after permanent prostate brachytherapy in prostate cancer
Urology
(2001)
S. Nag et al.
American Brachytherapy Society (ABS) recommendations for transperineal permanent brachytherapy of prostate cancer
Int J Radiat Oncol Biol Phys
(1999)
S.J. Feigenberg et al.
Health-related quality of life in men receiving prostate brachytherapy on RTOG 98-05
Int J Radiat Oncol Biol Phys
(2005)
W.R. Lee et al.
A descriptive analysis of postimplant dosimetric parameters from Radiation Therapy Oncology Group P0019
Brachytherapy
(2006)

There are more references available in the full text version of this article.

Cited by (50)

Endorectal contact radiation boosting: Making the case for dose AND volume reporting
2022, Brachytherapy
The various rectal endoluminal radiation techniques all have steep, but different, dose gradients. In rectal contact brachytherapy (CXB) doses are typically prescribed and reported to the applicator surface and not to the gross tumor volume (GTV), clinical target volume (CTV) or organs at risk (OAR), which is crucial to understand tumor response and toxicity rates. To quantify the above-described problem, we performed a dose modeling study using a fixed prescription dose at the surface of the applicator and varied tumor response scenarios.
Endorectal ultrasound-based 3D-volume-models of rectal tumors and the rectal wall were used to simulate the delivered dose to GTV, CTV and the rectal wall layers, assuming treatment with Maastro HDR contact applicator for rectal cancer with a fixed prescription dose to the applicator surface (equivalent to 3 × 30 Gy CXB) and various response scenarios.
An identical prescribed dose to the surface of the applicator resulted in a broad range of doses delivered to the GTV, CTV and the uninvolved intestinal wall. For example, the equieffective dose in 2 Gy per fraction (EQD2) D90% of the GTV varied between 63 and 231 Gy, whereas the EQD2 D2cc of the rectal wall varied between 97 and 165 Gy.
Doses prescribed at the surface are not representative of the dose received by the tumor and the bowel wall. This stresses the relevance of dose reporting and prescription to GTV and CTV volumes and OAR in order to gain insight between delivered dose, local control and toxicity and to optimize treatment protocols.
Iodine-125 radioactive seed brachytherapy as a treatment for spine and bone metastases: A systematic review and meta-analysis
2021, Surgical Oncology
To evaluate the analgesic efficacy, safety, and local tumor control of iodine-125 (¹²⁵I) seed brachytherapy (BT) for the management of spine and bone metastases.
A systematic literature search was conducted using PubMed, the Cochrane Library, and Scopus databases. Data regarding patient demographics, tumor characteristics, procedural parameters, and clinical outcomes were extracted and analyzed.
Fourteen studies (7 prospective, 7 retrospective) were included, accounting for 689 patients, in our review. Analgesic efficacy was assessed at baseline and various postoperative time points. Significant improvement in pain was noted at 4- and 24-week follow-ups (p < 0.01). Interestingly, all studies that combined ¹²⁵I seed BT with cement augmentation reported relatively higher levels of pain reduction (mean pain reduction ≥4 points) as compared to the studies which applied ¹²⁵I seed BT as a stand-alone therapy (mean pain reduction ≥2 points), at the last follow-up. Local tumor control rates ranged widely from 14% to 100% at varying follow-ups. Median overall survival ranged between 10 months and 25 months. The overall complication rate was 19% (130/689) and mainly included minor subcutaneous hemorrhage, fever, myelosuppression, and seed displacement. Metrics assessing performance and quality of life demonstrated significant improvements from baseline to posttreatment.
¹²⁵I seed BT, alone or in conjunction with cement augmentation, may be a viable salvage therapy in appropriately selected patients. However, further studies are needed to analyze the long-term efficacy of this intervention as a palliative and curative modality.
Nomograms are key decision-making tools in prostate cancer radiation therapy
2018, Urologic Oncology: Seminars and Original Investigations
The use of nomograms for predicting clinical endpoints has been well documented. Nomograms provide an individualized prognosis and help clinicians determine the effectiveness of treatment for a given patient. Early identification of potential treatment failure or toxicity allows alternative approaches to be considered, reducing unnecessary treatment, morbidity, and cost. This review aims to evaluate clinical potential of nomogram use for the management of prostate cancer radiotherapy patients.
PubMed, Embase, and Scopus were searched for literature published between 2006 and 2016. The reported correlation between measured and nomogram-predicted probabilities of biochemical control, disease progression, survival and toxicity was reviewed, through an analysis of concordance indexes and areas under the curves.
Sixteen studies were reviewed. Outcomes predicted by the nomogram were very close to outcomes measured (concordance index of 0.7 and above) in the majority. But a combination of under and overestimation of outcome was also reported. The predictive accuracy of nomograms was very variable, however, most nomograms had accuracy greater than chance, indicated by a concordance index higher than 0.5.
Nomograms can be used as prognostic guides to aid clinical decision-making for prostate cancer patients until further research addresses the limitations presented in this review. Strict definitions of end points should be added to future models and perhaps models could be enhanced with the incorporation of genomic variables or tumor specific parameters.
DNA-PKcs Expression Is a Predictor of Biochemical Recurrence After Permanent Iodine 125 Interstitial Brachytherapy for Prostate Cancer
2016, International Journal of Radiation Oncology Biology Physics
Predictive factors for biochemical recurrence (BCR) in localized prostate cancer (PCa) after brachytherapy are insufficient to date. Cellular radiosensitivity depends on DNA double-strand breaks, mainly repaired by the nonhomologous end-joining (NHEJ) system. We analyzed whether the expression of NHEJ proteins can predict BCR in patients treated by brachytherapy for localized PCa.
From 983 PCa cases treated by brachytherapy between March 2000 and March 2012, 167 patients with available biopsy material suitable for in situ analysis were included in the study. The median follow-up time was 47 months. Twenty-nine patients experienced BCR. All slides were reviewed to reassess the Gleason score. Expression of the key NHEJ proteins DNA-PKcs, Ku70, and Ku80, and the proliferation marker Ki67, was studied by immunohistochemistry performed on tissue microarrays.
The Gleason scores after review (P=.06) tended to be associated with BCR when compared with the score initially reported (P=.74). Both the clinical stage (P=.02) and the pretreatment prostate-specific antigen level (P=.01) were associated with biochemical failure. Whereas the expression of Ku80 and Ki67 were not predictive of relapse, positive DNA-PKcs nuclear staining (P=.003) and higher Ku70 expression (P=.05) were associated with BCR. On multivariate analysis, among pretreatment variables, only DNA-PKcs (P=.03) and clinical stage (P=.02) remained predictive of recurrence. None of the patients without palpable PCa and negative DNA-PKcs expression experienced biochemical failure, compared with 32% of men with palpable and positive DNA-PKcs staining that recurred.
Our results suggest that DNA-PKcs could be a predictive marker of BCR after brachytherapy, and this might be a useful tool for optimizing the choice of treatment in low-risk PCa patients.
Is Surgery Still Necessary for Prostate Cancer?
2016, Prostate Cancer: Science and Clinical Practice: Second Edition
Management options of localized prostate cancer principally include active surveillance and active treatment options including radical prostatectomy (RP) and radiation therapies (RT). Treatment should be tailored to each patient, taking in consideration the patient’s overall health, life expectancy, and disease risk; clinicians’ skills and experience; and the patients’ preferences and priorities. Comparative effectiveness research on these different treatments is crucial with regard to oncological efficacy, short- and long-term side effects, effects on health-related quality of life (HRQOL), and cost. Multiple well-conducted, retrospective studies suggest better cancer-specific and overall survival for RP compared to RT, especially for higher-risk disease. HRQOL outcomes are not clearly better for one modality over the other, and costs generally favor surgery over radiation. RP should be considered, particularly in the context of multimodal treatment strategies, for men with high-risk disease. Treatments need to be targeted to the patients most likely to benefit, and the way forward likely will involve more use of active surveillance for low-risk disease and multimodal treatment for high-risk disease.
The Importance of Prostate-specific Antigen (PSA) Nadir and Early Identification of PSA Relapse after 10 Years of Prostate Iodine<sup>125</sup> Seed Brachytherapy in Edinburgh
2015, Clinical Oncology
To analyse our 5 and 10 year prostate brachytherapy outcome data and to assess the impact of PSA nadir on relapse free survival and whether an alternative definition of PSA relapse could detect men destined to fail by the Phoenix definition at an earlier time point.
474 men were treated over a 10 year period between 20012 and 2011and divided into 2 five year cohorts for the purpose of the analysis.
The risk of relapse is strongly predicted by post treat prostate-specific antigen (PSA) nadir. After 3 years post-treatment, PSA nadir plus 0.4 ng/ml identified men at risk of relapse 17 months earlier than the Phoenix definition.
The Phoenix definition of nadir plus 2.0 ng/ml does not allow the early identification of men destined to relapse. The initiation of salavage therapy at the earliest opportunity could potentially affect subsequent survival and an outline randomised controlled trial proposal is presented.

View all citing articles on Scopus

: Conflict of interest: R.S. acts as a consultant for Bard. B.D. acts as a consultant for Oncura Inc. and Calypso Inc. and has a financial interest in Tomotherapy Inc. N.S. is a co-owner of Prologics, LLC. No other conflicts.

View full text

Clinical InvestigationPostoperative Nomogram Predicting the 9-Year Probability of Prostate Cancer Recurrence After Permanent Prostate Brachytherapy Using Radiation Dose as a Prognostic Variable

Purpose

Methods and Materials

Results

Conclusion

Introduction

Section snippets

Methods and Materials

Results

Discussion

Pretreatment nomogram for predicting freedom from recurrence after permanent prostate brachytherapy in prostate cancer

Urology

American Brachytherapy Society (ABS) recommendations for transperineal permanent brachytherapy of prostate cancer

Int J Radiat Oncol Biol Phys

Health-related quality of life in men receiving prostate brachytherapy on RTOG 98-05

Int J Radiat Oncol Biol Phys

A descriptive analysis of postimplant dosimetric parameters from Radiation Therapy Oncology Group P0019

Brachytherapy

Clinical Investigation
Postoperative Nomogram Predicting the 9-Year Probability of Prostate Cancer Recurrence After Permanent Prostate Brachytherapy Using Radiation Dose as a Prognostic Variable