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Title: Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer

Abstract

Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Methods and Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement, PCL {>=} or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Results: Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL {>=}40% (89% vs. 68 %, p = 0.04) were found to be significant predictors formore » LR, although PCL {>=}40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL {>=}40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. Conclusions: LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.« less

Authors:
 [1];  [2];  [3];  [2];  [4];  [3];  [2];  [3];  [2];  [2]; ; ; ;  [1];  [2]; ;  [1];  [2]; ;  [1] more »;  [2];  [1];  [2] « less
  1. Department of Radiation Oncology, University of Toronto, Toronto (Canada)
  2. (Canada)
  3. Princess Margaret Hospital, University Health Network, Toronto (Canada)
  4. Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto (Canada)
Publication Date:
OSTI Identifier:
22056126
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 82; Journal Issue: 3; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The 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; BIOPSY; CLINICAL TRIALS; FAILURES; FORECASTING; HAZARDS; MEN; NEOPLASMS; PATIENTS; PROSTATE; RADIATION DOSES; RADIOTHERAPY

Citation Formats

Chopra, Supriya, Princess Margaret Hospital, University Health Network, Toronto, Toi, Ants, Department of Medical Imaging, University of Toronto, Toronto, Taback, Nathan, Evans, Andrew, Department of Pathology, University of Toronto, Toronto, Haider, Masoom A., Department of Medical Imaging, University of Toronto, Toronto, Sunnybrook Health Sciences Center, Toronto, Milosevic, Michael, Bristow, Robert G., Chung, Peter, Bayley, Andrew, Princess Margaret Hospital, University Health Network, Toronto, Morton, Gerard, Vesprini, Danny, Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Warde, Padraig, Catton, Charles, Princess Margaret Hospital, University Health Network, Toronto, Menard, Cynthia, E-mail: Cynthia.Menard@rmp.uhn.on.ca, and Princess Margaret Hospital, University Health Network, Toronto. Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer. United States: N. p., 2012. Web. doi:10.1016/J.IJROBP.2011.05.035.
Chopra, Supriya, Princess Margaret Hospital, University Health Network, Toronto, Toi, Ants, Department of Medical Imaging, University of Toronto, Toronto, Taback, Nathan, Evans, Andrew, Department of Pathology, University of Toronto, Toronto, Haider, Masoom A., Department of Medical Imaging, University of Toronto, Toronto, Sunnybrook Health Sciences Center, Toronto, Milosevic, Michael, Bristow, Robert G., Chung, Peter, Bayley, Andrew, Princess Margaret Hospital, University Health Network, Toronto, Morton, Gerard, Vesprini, Danny, Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Warde, Padraig, Catton, Charles, Princess Margaret Hospital, University Health Network, Toronto, Menard, Cynthia, E-mail: Cynthia.Menard@rmp.uhn.on.ca, & Princess Margaret Hospital, University Health Network, Toronto. Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer. United States. doi:10.1016/J.IJROBP.2011.05.035.
Chopra, Supriya, Princess Margaret Hospital, University Health Network, Toronto, Toi, Ants, Department of Medical Imaging, University of Toronto, Toronto, Taback, Nathan, Evans, Andrew, Department of Pathology, University of Toronto, Toronto, Haider, Masoom A., Department of Medical Imaging, University of Toronto, Toronto, Sunnybrook Health Sciences Center, Toronto, Milosevic, Michael, Bristow, Robert G., Chung, Peter, Bayley, Andrew, Princess Margaret Hospital, University Health Network, Toronto, Morton, Gerard, Vesprini, Danny, Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto, Warde, Padraig, Catton, Charles, Princess Margaret Hospital, University Health Network, Toronto, Menard, Cynthia, E-mail: Cynthia.Menard@rmp.uhn.on.ca, and Princess Margaret Hospital, University Health Network, Toronto. 2012. "Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer". United States. doi:10.1016/J.IJROBP.2011.05.035.
@article{osti_22056126,
title = {Pathological Predictors for Site of Local Recurrence After Radiotherapy for Prostate Cancer},
author = {Chopra, Supriya and Princess Margaret Hospital, University Health Network, Toronto and Toi, Ants and Department of Medical Imaging, University of Toronto, Toronto and Taback, Nathan and Evans, Andrew and Department of Pathology, University of Toronto, Toronto and Haider, Masoom A. and Department of Medical Imaging, University of Toronto, Toronto and Sunnybrook Health Sciences Center, Toronto and Milosevic, Michael and Bristow, Robert G. and Chung, Peter and Bayley, Andrew and Princess Margaret Hospital, University Health Network, Toronto and Morton, Gerard and Vesprini, Danny and Odette Cancer Center, Sunnybrook Health Sciences Center, Toronto and Warde, Padraig and Catton, Charles and Princess Margaret Hospital, University Health Network, Toronto and Menard, Cynthia, E-mail: Cynthia.Menard@rmp.uhn.on.ca and Princess Margaret Hospital, University Health Network, Toronto},
abstractNote = {Purpose: Rational design of targeted radiotherapy (RT) in prostate cancer (Pca) hinges on a better understanding of spatial patterns of recurrence. We sought to identify pathological factors predictive for site of local recurrence (LR) after external beam RT. Methods and Materials: Prospective databases were reviewed to identify men with LR after RT from 1997 through 2009. Patients with biochemical failure and biopsy-confirmed Pca more than 2 years after RT were evaluated. Prediction for site of recurrence based on the following pretreatment factors was determined on independent and cluster-sextant basis: presence of malignancy, dominant vs. nondominant percentage core length (PCL) involvement, PCL {>=} or <40%, and Gleason score. Sites of dominant PCL were defined as sextants with peak PCL involvement minus 10%, and >5% for each patient. Results: Forty-one patients with low-intermediate risk Pca constituted the study cohort. Median time to biopsy after RT was 51 months (range, 24-145). Of 246 sextants, 74 were involved with tumor at baseline. When sextants are treated as independent observations the presence of malignancy (77% vs. 22%, p = 0.0001), dominant PCL (90% vs. 46%, p = 0.0001), and PCL {>=}40% (89% vs. 68 %, p = 0.04) were found to be significant predictors for LR, although PCL {>=}40% did not retain statistical significance if sextants were considered correlated. The vast majority of patients (95%) recurred at the original site of dominant PCL or PCL {>=}40%, and 44% also recurred in regions of nondominant PCL <40% (n = 8) and/or benign sampling (n = 14) at baseline. Conclusions: LR after RT predominantly occurs in regions bearing higher histological tumor burden but are not isolated to these sites. Our data highlights the value of spatially resolved baseline pathological sampling and may assist in the design of clinical trials tailoring RT dose prescriptions to subregions of the prostate gland.},
doi = {10.1016/J.IJROBP.2011.05.035},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 82,
place = {United States},
year = 2012,
month = 3
}
  • Purpose: The aim of this study was to evaluate the feasibility and safety of salvage high-dose-rate (HDR) brachytherapy for locally recurrent prostate cancer after external beam radiotherapy (EBRT). Methods and Materials: We retrospectively analyzed 21 consecutively accrued patients undergoing salvage HDR brachytherapy for locally recurrent prostate cancer after EBRT between November 1998 and December 2005. After pathologic confirmation of locally recurrent disease, all patients were treated with 36 Gy in six fractions using two transrectal ultrasound-guided HDR prostate implants, separated by 1 week. Eleven patients received neoadjuvant hormonal therapy immediately presalvage, whereas none received adjuvant hormonal therapy postsalvage. Median follow-upmore » time from recurrence was 18.7 months (range, 6-84 months). Determination of subsequent biochemical failure after brachytherapy was based on the definition by the American Society for Therapeutic Radiology and Oncology. Results: Based on the Common Terminology Criteria for Adverse Events (CTCAE version 3), 18 patients reported Grade 1 to 2 genitourinary symptoms by 3 months postsalvage. Three patients developed Grade 3 genitourinary toxicity. Maximum observed gastrointestinal toxicity was Grade 2; all cases spontaneously resolved. The 2-year Kaplan-Meier estimate of biochemical control after recurrence was 89%. Thirteen patients have achieved a PSA nadir {<=}0.1 ng/ml, but at the time of writing this endpoint has not yet been reached for all patients. All patients are alive; however 2 have experienced biochemical failure, both with PSA nadirs {>=}1, and have subsequently been found to have distant metastases. Conclusions: Salvage HDR prostate brachytherapy appears to be feasible and effective.« less
  • Purpose: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. Methods and Materials: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm{sup 3} and/or resulting inmore » extraprostatic disease on pathology were considered clinically significant. Results: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm{sup 3}) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci ({<=}0.06 cm{sup 3}) were not detected on imaging. The ratios between tumor volumes on pathology and on post-RT MRI ranged from 0.52 to 2.80. Conclusions: Our study provides a direct visual confirmation that clinically significant post-RT local recurrence occurs at the site of primary tumor. Our results are in agreement with reported clinical and pathologic results and support the current practice of boosting the radiation dose within the primary tumor using imaging guidance. They also suggest that monitoring of primary tumor with pre-RT and post-RT MRI could lead to early detection of local recurrence amenable to salvage treatment.« less
  • Purpose: To determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and Materials: This retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, andmore » size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. Results: Nine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1-2.2) and 1.9 cm (range, 1.4-2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7-10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). Conclusions: Local recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.« less
  • Purpose: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. Methods and Materials: We evaluated 390 patients with pT{sub 3}N{sub 0} prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 yearsmore » after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. Results: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3). Conclusions: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT{sub 3}N{sub 0} PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to aRT, delivered to the prostatic bed.« less
  • Purpose: To identify factors predictive for chronic urinary toxicity secondary to high-dose adaptive three-dimensional conformal radiation. Methods and Materials: From 1999 to 2002, 331 consecutive patients with clinical Stage II-III prostate cancer were prospectively treated (median dose, 75.6 Gy). The bladder was contoured, and the bladder wall was defined as the outer 3 mm of the bladder solid volume. Toxicity was quantified according to the National Cancer Institute Common Toxicity Criteria 2.0. Median follow-up was 1.6 years. Results: The 3-year rates of Grade {>=}2 and Grade 3 chronic urinary toxicity were 17.0% and 3.6%, respectively. Prostate volume, confidence-limited patient-specific planningmore » target volume, bladder wall volume, and acute urinary toxicity were all found to be accurate predictors for chronic urinary toxicity. The volume of bladder wall receiving {>=}30 Gy (V30) and {>=}82 Gy (V82), along with prostate volume, were all clinically useful predictors of Grade {>=}2 and Grade 3 chronic urinary toxicity and chronic urinary retention. Both Grade {>=}2 (p = 0.001) and Grade 3 (p = 0.03) acute urinary toxicity were predictive for the development of Grade {>=}2 (p = 0.001, p = 0.03) and Grade 3 (p = 0.05, p < 0.001) chronic urinary toxicity. On Cox multivariate analysis the development of acute toxicity was independently predictive for the development of both Grade {>=}2 and Grade 3 chronic urinary toxicity. Conclusions: Acute urinary toxicity and bladder wall dose-volume endpoints are strong predictors for the development of subsequent chronic urinary toxicity. Our recommendation is to attempt to limit the bladder wall V30 to <30 cm{sup 3} and the V82 to <7 cm{sup 3} when possible. If bladder wall information is not available, bladder solid V30 and V82 may be used.« less