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Title: Long-Term Results and Predictive Factors of Three-Dimensional Conformal Salvage Radiotherapy for Biochemical Relapse After Prostatectomy

Abstract

Purpose: Salvage radiotherapy (RT) is used to treat patients with biochemical failure after radical prostatectomy (RP). Although retrospective series have demonstrated that salvage RT will result in biochemical response in approximately 75% of patients, long-term response is much lower (20-40%). The purpose of this study was to determine prognostic factors related to the prostate-specific antigen (PSA) outcome after salvage RT. Methods and Materials: Between 1991 and 2004, 171 patients received salvage RT at University of Heidelberg. Patient age, margin status, Gleason score, tumor grading, pathologic tumor stage, pre-RP and pre-RT PSA levels, and time from RP to rise of PSA were analyzed. Results: Median follow-up time was 39 months. The 5-year overall and clinical relapse-free survival were 93.8% and 80.8%, respectively. After RT serum PSA decreased in 141 patients (82.5%). The 5-year biochemical relapse-free survival was 35.1%. Univariate analysis showed following statistically significant predictors of PSA recurrence after RT: preoperative PSA level (p = 0.035), pathologic tumor classification (p 0.001), Gleason score (p < 0.001), tumor grading (p = 0.004), and pre-RT PSA level (p = 0.031). On multivariate analysis, only Gleason score (p = 0.047) and pre-RT PSA level (p = 0.049) were found to be independently predictive ofmore » PSA recurrence. Conclusions: This study represents one of the largest retrospective studies analyzing the outcome of patients treated with salvage RT at a single institution. Our findings suggest that patients with Gleason score <7 and low pre-RT PSA levels are the best candidates for salvage RT, whereas patients with high-grade lesions should be considered for additional treatment (e.g., hormonal therapy)« less

Authors:
 [1];  [2];  [2];  [2];  [3];  [3]
  1. Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany). E-mail: dirk.neuhof@med.uni-heidelberg.de
  2. Department of Radiation Oncology, University of Heidelberg, Heidelberg (Germany)
  3. Department of Urology, University of Heidelberg, Heidelberg (Germany)
Publication Date:
OSTI Identifier:
20951585
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 67; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2006.11.024; PII: S0360-3016(06)03513-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ANTIGENS; CARCINOMAS; FAILURES; HORMONES; MULTIVARIATE ANALYSIS; PATIENTS; PROSTATE; RADIOTHERAPY

Citation Formats

Neuhof, Dirk, Hentschel, Tina, Bischof, Marc, Sroka-Perez, Gabriele, Hohenfellner, Markus, and Debus, Juergen. Long-Term Results and Predictive Factors of Three-Dimensional Conformal Salvage Radiotherapy for Biochemical Relapse After Prostatectomy. United States: N. p., 2007. Web. doi:10.1016/j.ijrobp.2006.11.024.
Neuhof, Dirk, Hentschel, Tina, Bischof, Marc, Sroka-Perez, Gabriele, Hohenfellner, Markus, & Debus, Juergen. Long-Term Results and Predictive Factors of Three-Dimensional Conformal Salvage Radiotherapy for Biochemical Relapse After Prostatectomy. United States. doi:10.1016/j.ijrobp.2006.11.024.
Neuhof, Dirk, Hentschel, Tina, Bischof, Marc, Sroka-Perez, Gabriele, Hohenfellner, Markus, and Debus, Juergen. Sun . "Long-Term Results and Predictive Factors of Three-Dimensional Conformal Salvage Radiotherapy for Biochemical Relapse After Prostatectomy". United States. doi:10.1016/j.ijrobp.2006.11.024.
@article{osti_20951585,
title = {Long-Term Results and Predictive Factors of Three-Dimensional Conformal Salvage Radiotherapy for Biochemical Relapse After Prostatectomy},
author = {Neuhof, Dirk and Hentschel, Tina and Bischof, Marc and Sroka-Perez, Gabriele and Hohenfellner, Markus and Debus, Juergen},
abstractNote = {Purpose: Salvage radiotherapy (RT) is used to treat patients with biochemical failure after radical prostatectomy (RP). Although retrospective series have demonstrated that salvage RT will result in biochemical response in approximately 75% of patients, long-term response is much lower (20-40%). The purpose of this study was to determine prognostic factors related to the prostate-specific antigen (PSA) outcome after salvage RT. Methods and Materials: Between 1991 and 2004, 171 patients received salvage RT at University of Heidelberg. Patient age, margin status, Gleason score, tumor grading, pathologic tumor stage, pre-RP and pre-RT PSA levels, and time from RP to rise of PSA were analyzed. Results: Median follow-up time was 39 months. The 5-year overall and clinical relapse-free survival were 93.8% and 80.8%, respectively. After RT serum PSA decreased in 141 patients (82.5%). The 5-year biochemical relapse-free survival was 35.1%. Univariate analysis showed following statistically significant predictors of PSA recurrence after RT: preoperative PSA level (p = 0.035), pathologic tumor classification (p 0.001), Gleason score (p < 0.001), tumor grading (p = 0.004), and pre-RT PSA level (p = 0.031). On multivariate analysis, only Gleason score (p = 0.047) and pre-RT PSA level (p = 0.049) were found to be independently predictive of PSA recurrence. Conclusions: This study represents one of the largest retrospective studies analyzing the outcome of patients treated with salvage RT at a single institution. Our findings suggest that patients with Gleason score <7 and low pre-RT PSA levels are the best candidates for salvage RT, whereas patients with high-grade lesions should be considered for additional treatment (e.g., hormonal therapy)},
doi = {10.1016/j.ijrobp.2006.11.024},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 67,
place = {United States},
year = {Sun Apr 01 00:00:00 EDT 2007},
month = {Sun Apr 01 00:00:00 EDT 2007}
}
  • Purpose: To evaluate the long-term failure patterns in patients who underwent an {sup 111}In-capromab pendetide (ProstaScint) scan as part of their pretreatment assessment for a rising prostate-specific antigen (PSA) level after prostatectomy and subsequently received local radiotherapy (RT) to the prostate bed. Methods: Fifty-eight patients were referred for evaluation of a rising PSA level after radical prostatectomy. All patients had negative findings for metastatic disease after abdominal/pelvis imaging with CT and isotope bone scans. All patients underwent a capromab pendetide scan, and the sites of uptake were noted. All patients were treated with local prostate bed RT (median dose 66.6more » Gy). Results: Of the 58 patients, 20 had biochemical failure (post-RT PSA level >0.2 ng/mL or a rise to greater than the nadir PSA), including 6 patients with positive uptake outside the bed (positive elsewhere). The 4-year biochemical relapse-free survival (bRFS) rates for patients with negative (53%), positive in the prostate bed alone (45%), or positive elsewhere (74%) scan findings did not differ significantly (p = 0.51). The positive predictive value of the capromab pendetide scan in detecting disease outside the bed was 27%. The capromab pendetide scan status had no effect on bRFS. Those with a pre-RT PSA level of <1 ng/mL had improved bRFS (p = 0.003). Conclusion: The capromab pendetide scan has a low positive predictive value in patients with positive elsewhere uptake and the 4-year bRFS was similar to that for those who did not exhibit positive elsewhere uptake. Therefore, patients with a postprostatectomy rising PSA level should considered for local RT on the basis of clinicopathologic factors.« less
  • Purpose: To assess the acute and late gastrointestinal (GI) and genitourinary (GU) toxicity of salvage radiotherapy (RT). Methods and Materials: A total of 75 patients with prostate-specific antigen relapse or clinically isolated local recurrence after radical prostatectomy were accrued between 1998 and 2002 for a Phase II study to evaluate the efficacy of salvage RT plus 2-year androgen suppression. Acute and late GI and GU toxicity was prospectively assessed using the National Cancer Institute Expanded Common Toxicity Criteria Version 2. For acute toxicity, prevalence was examined. For late toxicity, cumulative incidences of Grade 2 or higher and Grade 3 toxicitymore » were calculated. Results: Median age was 67 years at the time of salvage RT. Median time from radical prostatectomy to RT was 36.2 months. Median follow-up was 45.1 months. Seventy-five patients were available for acute toxicity analysis, and 72 for late toxicity. Twelve percent and 40% had preexisting GI and GU dysfunction before RT, respectively. Sixty-eight percent, 21%, and 5% experienced Grade 1, 2, and 3 acute GI or GU toxicity, respectively. Cumulative incidences of Grade 2 or higher late GI and GU toxicity at 36 months were 8.7% and 22.6%, and Grade 3 late GI and GU toxicity, 1.6% and 2.8%, respectively. None had Grade 4 late toxicity. The severity of acute GU toxicity (Grade < 2 vs. {>=} 2) was a significant predictor factor for Grade 2 or higher late GU toxicity after adjusting for preexisting GU dysfunction. Conclusion: Salvage RT generally was well tolerated. Grade 3 or higher late GI or GU toxicity was uncommon.« less
  • Purpose: To compare the biochemical relapse-free survival (bRFS) among patients receiving whole pelvic radiotherapy (WPRT) vs. prostate bed RT (PBRT) after radical prostatectomy. Methods and Materials: Between 1985 and 2005, 160 patients underwent adjuvant or salvage RT after radical prostatectomy. A short course of total androgen suppression was also given concurrently to 87 patients. Of the 160 patients, 114 were considered at high risk of lymph node involvement because they had a pathologic Gleason score of {>=}8, a preoperative prostate-specific antigen level >20 ng/mL, seminal vesicle or prostate capsule involvement, or pathologic lymph node involvement. Of this group, 72 underwentmore » WPRT and 42 underwent PBRT. The median follow-up was >5 years for all patient subsets. Kaplan-Meier and Cox proportional hazards multivariate analyses were performed for all clinical, pathologic, and treatment factors predicting for bRFS. Results: Whole pelvic RT resulted in superior bRFS compared with PBRT (p = 0.03). The advantage of WPRT was limited to high-risk patients, with a 5-year bRFS rate of 47% (95% confidence interval, 35-59%) after WPRT vs. 21% (95% confidence interval, 8-35%) after PBRT (p = 0.008). For low-risk patients, no difference (p = 0.9) was found. On multivariate analysis, only WPRT (p = 0.02) and a preoperative prostate-specific antigen level <1.0 ng/mL (p = 0.002) were significantly associated with bRFS. The benefit from total androgen suppression with postoperative RT was only observed when given concurrently with WPRT (p 0.04) and not with PBRT (p = 0.4). Conclusion: The results of our study have indicated that WPRT confers superior bRFS compared with PBRT for high-risk patients receiving adjuvant or salvage RT after radical prostatectomy. This advantage was observed only with concurrent TAS. These results are analogous to the benefit from WPRT seen in the Radiation Therapy Oncology Group 94-13 study.« less
  • Purpose: This study attempts to improve our understanding of the role of salvage radiotherapy (SRT) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy with regard to biochemical control, rate of distant metastasis, and survival. Methods and Materials: We performed a retrospective analysis of 96 men treated with conformal prostate bed SRT (median, 64.8 Gy) at a single institution (median follow-up, 70 months). The majority had intermediate- or high-risk prostate cancer. Fifty-four percent underwent a resection with positive margins (R1 resection). The median time interval between surgery and SRT was 22 months. Results: After SRT, 66% of patients reachedmore » a PSA nadir of less than 0.2 ng/mL. However, the 5-year biochemical no evidence of disease rate was 35%. Seminal vesicle involvement was predictive for a significantly lower biochemical no evidence of disease rate. All patients with a preoperative PSA level greater than 50 ng/mL relapsed biochemically within 2 years. The 5-year distant metastasis rate was 18%, the 5-year prostate cancer-specific survival rate was 90%, and the 5-year overall survival rate was 88%. Significantly more distant metastases developed in patients with a PSA nadir greater than 0.05 ng/mL after SRT, and they had significantly inferior prostate cancer-specific and overall survival rates. Resection status (R1 vs. R0) was not predictive for any of the endpoints. Conclusions: Men with postoperative PSA relapse can undergo salvage treatment by prostate bed radiotherapy, but durable PSA control is maintained only in about one-third of the patients. Despite a high biochemical failure rate after SRT, prostate cancer-specific survival does not decrease rapidly.« less
  • Purpose: Permanent prostate implant brachytherapy (PPI), three-dimensional conformal radiotherapy (3D-CRT), and conformal proton beam radiotherapy (CPBRT) are used in the treatment of localized prostate cancer, although no head-to-head trials have compared these modalities. We studied the biochemical control (biochemical no evidence of disease [bNED]) and prostate-specific antigen (PSA) nadir achieved with contemporary PPI, and evaluated it against 3D-CRT and CPBRT. Patients and Methods: A total of 249 patients were treated with PPI at the University of California, San Francisco, and the outcomes were compared with those from a 3D-CRT cohort and the published results of a high-dose CPBRT boost (CPBRTB)more » trial. For each comparison, subsets of the PPI cohort were selected with patient and disease criteria similar to those of the reference group. Results: With a median follow-up of 5.3 years, the bNED rate at 5 and 7 years achieved with PPI was 92% and 86%, respectively, using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition, and 93% using the PSA nadir plus 2 ng/mL definition. Using the ASTRO definition, a 5-year bNED rate of 78% was achieved for the 3D-CRT patients compared with 94% for a comparable PPI subset and 93% vs. 92%, respectively, using the PSA nadir plus 2 ng/mL definition. The median PSA nadir for patients treated with PPI and 3D-CRT was 0.10 and 0.40 ng/mL, respectively (p < .0001). For the CPBRT comparison, the 5-year bNED rate after a CPBRTB was 91% using the ASTRO definition vs. 93% for a similar group of PPI patients. A greater proportion of PPI patients achieved a lower PSA nadir compared with those achieved in the CPBRTB trial (PSA nadir <=0.5 ng/mL, 91% vs. 59%, respectively). Conclusion: We have demonstrated excellent outcomes in low- to intermediate-risk patients treated with PPI, suggesting at least equivalent 5-year bNED rates and a greater proportion of men achieving lower PSA nadirs compared with 3D-CRT or CPBRTB.« less