Prostatic Neoplasms: D'Amico AV

Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen CM, Anonymous00324. · American Urological Association Education and Research, Inc. · J Urol. · Pubmed #17509297 No free full text.

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Scher HI, Eisenberger M, D'Amico AV, Halabi S, Small EJ, Morris M, Kattan MW, Roach M, Kantoff P, Pienta KJ, Carducci MA, Agus D, Slovin SF, Heller G, Kelly WK, Lange PH, Petrylak D, Berg W, Higano C, Wilding G, Moul JW, Partin AN, Logothetis C, Soule HR. · Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. · J Clin Oncol. · Pubmed #14752077 No free full text.

Abstract: PURPOSE: To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA). RESULTS: Hypothesis: A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population. Patient Population: The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed. Intervention: Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation. Outcomes: An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned. Trial Design: The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative. CONCLUSION: Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.

D'Amico AV. · No affiliation provided · J Clin Oncol. · Pubmed #18281649 No free full text.

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D'Amico AV. · No affiliation provided · J Clin Oncol. · Pubmed #17194901 No free full text.

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D'Amico AV. · No affiliation provided · Cancer. · Pubmed #15637686 links to  free full text

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D'Amico AV. · No affiliation provided · Cancer. · Pubmed #12412155 links to  free full text

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D'Amico AV. · No affiliation provided · J Clin Oncol. · Pubmed #12149288 No free full text.

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D'Amico AV, Vogelzang NJ. · No affiliation provided · Cancer. · Pubmed #10547533 links to  free full text

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D'Amico AV. · No affiliation provided · Urology. · Pubmed #10443710 No free full text.

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Nanda A, D'Amico AV. · Harvard Radiation Oncology Program, Brigham & Women's Hospital/Dana-Farber Cancer Institute, Boston, MA, USA. · BJU Int. · Pubmed #18778343 No free full text.

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Albert M, Song JS, Schultz D, Cormack RA, Tempany CM, Haker S, Devlin PM, Beard C, Hurwitz MD, Suh WW, Jolesz F, D'Amico AV. · Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Boston, MA 02115, USA. · Urol Oncol. · Pubmed #18312933 No free full text.

Abstract: PURPOSE: This study was performed to define the rectal dose constraint that would predict late rectal bleeding requiring argon plasma coagulation (APC) following prostate brachy mono-therapy. METHODS AND MATERIALS: Between February 1999 and April 2002, 91 patients with low risk prostate cancer underwent permanent I(125) radioactive seed implantation without the use of supplemental external beam radiation or androgen suppression therapy. Patients received both CT and MRI scans 6 weeks postimplant for evaluation of dosimetry. The CT and MRI scans were fused. Rectal volumes were contoured on the T2 weighted MR images. For those patients requiring APC, the date on which a patient reported rectal bleeding was recorded. A Cox regression analysis was performed to assess whether there was a significant association between the rectal volume (continuous) exceeding 100 Gy time rectal bleeding. Comparisons of estimates of rectal bleeding requiring APC were made using a 2-sided log rank test. RESULTS: There was a significant association (hazard ratio = 5.6 [95% confidence interval: 1.3, 23.8]; P = 0.002) between the rectal volume exceeding 100 Gy and rectal bleeding requiring APC. After a median follow-up of 4.25 (1-6) years, no patient with less than a median value of 8 cc of rectum exceeding 100 Gy required APC, whereas 20% (P = 0.004) were estimated to require APC within 3 years following treatment. CONCLUSIONS: Keeping the rectal volume receiving more than 100 Gy below 8 cc will minimize the risk of rectal bleeding requiring APC following I(125) permanent prostate brachy mono-therapy.

Sengupta S, Amling C, D'Amico AV, Blute ML. · Department of Urology, Mayo Clinic, Rochester, Minnesota 55905, USA. · J Urol. · Pubmed #18221963 No free full text.

Abstract: PURPOSE: We review the usefulness of prostate specific antigen kinetics (ie prostate specific antigen velocity and doubling time) in the treatment of patients with prostate cancer. MATERIALS AND METHODS: The MEDLINE database was searched to identify studies investigating prostate specific antigen kinetics in patients with prostate cancer. RESULTS: Various techniques are available for estimating prostate specific antigen kinetics, but to minimize the impact of prostate specific antigen variability on such calculations at least a 90-day period and preferably more than 2 measurements should be used. There is little to suggest which measure of prostate specific antigen kinetics may be superior since both appear to provide useful prognostic information. Prostate specific antigen velocity is easier to calculate but prostate specific antigen doubling time may have greater biological justification. Retrospective studies show that before treatment prostate specific antigen kinetics provide prognostic information regarding the risk of treatment failure and subsequent death from cancer. Additionally, in patients treated surgically preoperative prostate specific antigen kinetics predict the risk of adverse pathology, while in those undergoing conservative treatment prostate specific antigen kinetics are associated with the risk of progression and need for intervention. In patients with biochemical failure after therapy prostate specific antigen kinetics predict the risk and potential site of clinical recurrence, the likely response to salvage therapy, and the risk of death from cancer. Preliminary assessments also suggest that prostate specific antigen kinetics may serve as a surrogate end point to replace cancer specific mortality. CONCLUSIONS: Although prospective studies are lacking, the current literature suggests that prostate specific antigen kinetics provide valuable prognostic information, and should be further evaluated in clinical decision making and as a surrogate end point for future trials.

Nguyen PL, D'Amico AV, Lee AK, Suh WW. · Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. · Cancer. · Pubmed #17694553 links to  free full text

Abstract: Among men who experience prostate-specific antigen (PSA) failure after external beam radiation or brachytherapy (RT), many will harbor occult micrometastases; however, a significant minority will have a true local-only failure and, thus, potentially may benefit from a salvage local therapy. Those most likely to have a local-only failure initially have low-risk disease (PSA < 10 ng/mL, Gleason score < or =6, clinical T1c or T2a tumor status), pretreatment PSA velocity < 2.0 ng/mL per year at the time of initial presentation, interval to PSA failure > 3 years, PSA doubling time > 12 months, negative bone scan and pelvic imaging, and positive rebiopsy. In addition, men with presalvage PSA levels > 10 ng/mL, presalvage T3/T4 disease, or presalvage Gleason scores > or =7 on a rebiopsy sample without significant RT effects are unlikely to be cured by salvage local therapy. Based on a review of all series of post-RT salvage prostatectomy, cryosurgery, and brachytherapy published in English since 1990, morbidity can be substantial. Although urinary incontinence appeared to be greater after salvage prostatectomy (41%) or cryosurgery (36%) than after brachytherapy (6%), patients who received salvage brachytherapy faced a 17% risk of grade 3 or 4 genitourinary complications and a fistula risk that averaged 3.4% across all series. From this review, the authors concluded that prospective randomized studies are needed to determine the relative efficacy of the 3 major local salvage modalities and that additional research is needed to identify factors associated with an increased risk of significant complications to improve patient selection and to augment the benefit/risk ratio associated with attempts to cure local-only recurrences after radiation therapy.

Burnett AL, Aus G, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus S, Liebert M, Moul JW, Tangen C, Thrasher JB, Thompson I, Anonymous00008. · The Johns Hopkins Hospital, 600 North Wolfe St., Marburg 407, Baltimore, Maryland 21287-2411, USA. · J Urol. · Pubmed #17570435 No free full text.

Abstract: PURPOSE: In conjunction with the assignment to update the Guidelines for Management of Clinically Localized Prostate Cancer, the American Urological Association Prostate Cancer Guideline Update Panel performed a side analysis of the reporting of erectile function outcomes in this clinical context as published in the medical literature. MATERIALS AND METHODS: Four National Library of Medicine PubMed(R) Services literature searches targeting articles published from 1991 through early 2004 were done to derive outcome reporting (efficacy or side effects) for the treatment of clinical stage T1 or T2 N0M0 prostate cancer. A database was constructed containing descriptions relating to erectile function as well as numerical frequency rates of complete erectile dysfunction, and partial and intact erectile function for various treatments. A literature review was also done, consisting of a PubMed Services search of current measures and protocols used for assessing erectile function outcomes and a survey of consensus opinion sources on the management of male sexual dysfunctions. RESULTS: Based on inclusion criteria 436 articles were selected. Of these articles database extraction from 100 pertaining to radical prostatectomy garnered various characterizations of erectile function, including qualitative descriptions, generic terminology and rating systems. Database extraction from 31 articles, in which results for at least 50 patients were reported, yielded ranges of rates for complete erectile dysfunction, partial erectile function and intact erectile function that were 26% to 100%, 16% to 48% and 9% to 86% for radical prostatectomy, 8% to 85%, 21% to 47% and 36% to 63% for external beam radiation, and 14% to 61%, 21% and 18% for interstitial radiation, respectively. The literature review showed an evolution in standards for studying and reporting erectile function outcomes. CONCLUSIONS: Clinical studies reporting erectile function outcomes after localized prostate cancer treatment often demonstrate poorly interpretable and inconsistent manners of assessment as well as widely disparate rates of erectile dysfunction and erectile function. Future studies must apply scientifically rigorous methodology and standard outcomes measures to advance this field of study.

Cookson MS, Aus G, Burnett AL, Canby-Hagino ED, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen C, Thrasher JB, Thompson I. · Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA. · J Urol. · Pubmed #17222629 No free full text.

Abstract: PURPOSE: The American Urological Association Prostate Guideline Update Panel was charged with updating the Guidelines for Clinically Localized Prostate Cancer. In assessing outcomes with treatment, it became apparent that a highly variable number of definitions exist with respect to biochemical recurrence. Herein, we review the variability in published definitions of biochemical recurrence and make recommendations directed toward improving this terminology by recommending a standard definition in patients treated with radical prostatectomy. MATERIALS AND METHODS: Four PubMed literature searches were performed between May 2001 and April, 2004 and covered articles published from 1991 through early 2004. The search terms included the MeSH major headings of prostate cancer and prostatic neoplasm. All potentially relevant articles were retrieved and a more detailed screen for relevance was performed. An article was considered relevant if it reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate cancer. Data extractors recorded the definition of biochemical recurrence and definitions were then collapsed into categories representing the same criteria. The results of biochemical failure were subcategorized by initial treatment. RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these, a total of 145 articles contained 53 different definitions of biochemical recurrence for those treated with radical prostatectomy. Of these, the most common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight variation thereof. In addition, a total of 208 articles reported 99 different definitions of biochemical failure among those treated with radiation therapy. Of these, the American Society for Therapeutic Radiology and Oncology definition (70) and/or a variation thereof was the most commonly reported. In total, 166 different definitions of biochemical failure were identified. Following radical prostatectomy, the Panel recommends defining biochemical recurrence as an initial serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of the American Society for Therapeutic Radiology and Oncology criteria for patients treated with radiation therapy and acknowledges that these criteria will soon be updated although not yet published. CONCLUSIONS: A high degree of variability in the definition of biochemical recurrence exists following treatment for localized prostate cancer. Strict definitions for biochemical recurrence are necessary to identify men at risk for disease progression and to allow meaningful comparisons among patients treated similarly. The Panel acknowledges the American Society for Therapeutic Radiology and Oncology criteria and future modifications thereof for those receiving radiation therapy and recommends the newly developed American Urological Association criteria for those treated with radical prostatectomy. The purpose for the establishment of this standard is for data reporting purposes and for comparison of similarly treated patients. It is not intended to represent a threshold value for which to initiate treatment. The Panel acknowledges that the clinical decision to initiate treatment will be dependent on multiple factors including patient and physician interaction rather than a specific prostate specific antigen threshold value.

D'Amico AV, Barry MJ. · Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. · J Urol. · Pubmed #17070238 No free full text.

Abstract: PURPOSE: We assessed whether the association between the larger changes in prostate specific antigen and high grade prostate cancer observed in the Prostate Cancer Prevention Trial can explain the increased detection of high grade prostate cancer in men randomized to finasteride vs placebo. MATERIALS AND METHODS: A literature review was performed to obtain evidence to develop a hypothesis that may explain the results of the Prostate Cancer Prevention Trial. RESULTS: On average finasteride halved prostate specific antigen. As shown by the Medical Therapy of Prostatic Symptoms study and Prostate Cancer Prevention Trial, it also decreased the annual median increase in prostate specific antigen from benign prostatic hyperplasia. Therefore, despite doubling prostate specific antigen during the first 3 years of the Prostate Cancer Prevention Trial, to have prostate specific antigen exceed 4 ng/ml and have a prostate biopsy recommended men receiving finasteride vs placebo required greater increases in prostate specific antigen, which was shown in the Prostate Cancer Prevention Trial to be associated with high grade disease (p < 0.001). Also, the decrease of the contribution to prostate specific antigen from benign prostatic hyperplasia by finasteride improved the performance characteristics of prostate specific antigen to detect Gleason score 7 or higher prostate cancer. CONCLUSIONS: By decreasing the contribution to prostate specific antigen from benign prostatic hyperplasia finasteride makes changes in prostate specific antigen more cancer specific. This effect may explain the increased detection of high grade prostate cancer in men randomized to finasteride in the Prostate Cancer Prevention Trial. How to best use prostate specific antigen to recommend biopsy in men on 5alpha-reductase inhibitors requires further study.

Lee AK, D'Amico AV. · The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1202, Houston, TX 77030-4009, USA. · J Clin Oncol. · Pubmed #16278472 No free full text.

Abstract: A detectable and rising prostate-specific antigen (PSA) level after radical prostatectomy or a rising PSA above the nadir value after radiation therapy may represent a local failure, distant failure, or both. Determining the site or sites of failure is critical for selecting the appropriate salvage therapy. Nevertheless, although PSA failure precedes clinically evident failure by several years, determining the source of the biochemical failure is often not possible using currently available diagnostic studies. Selecting the optimal therapeutic approach may be guided by the initial clinical factors (eg, T-category, PSA, biopsy Gleason score). If the patient has had a radical prostatectomy, then the pathologic outcomes of the surgery (eg, pathologic T-category and prostatectomy Gleason score, nodal and margin status) may provide further information. Beyond pretreatment clinical and post-treatment pathologic factors, PSA kinetics, and specifically a pretreatment PSA velocity > 2 ng/mL/year, an interval to PSA failure < 3 years and a post-treatment PSA doubling time < 3 months place a man at increased risk for metastases and subsequent prostate cancer-specific mortality, making these men poor candidates for local-only salvage therapy. Therefore, the optimal candidate for local-only salvage therapy is a man whose pretreatment PSA velocity was 2 ng/mL/year or less, interval to PSA failure exceeds 3 years, and post-treatment PSA doubling time is at least 12 months, and who did not have biopsy or prostatectomy Gleason score of 8 to 10 or seminal vesicle or lymph node involvement.

Carroll PR, Chan JM, D'Amico AV, Gelmann EP, Iversen P, Klotz L, Nelson JB, Nelson PS, Nelson WG, Oh WK, Rosen N, Rubin MA, Sandler H, Sellers WR, Smith MR, Xu J, McMann MC, Kantoff PW. · Department of Urology, University of California School of Medicine, San Francisco 94115-1711, USA. · J Urol. · Pubmed #15535434 No free full text.

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Kelloff GJ, Coffey DS, Chabner BA, Dicker AP, Guyton KZ, Nisen PD, Soule HR, D'Amico AV. · Division of Cancer Treatment and Diagnostics, National Cancer Institute, Bethesda, Maryland 20892, USA. · Clin Cancer Res. · Pubmed #15173102 links to  free full text

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Carroll PR, Benaron DA, Blackledge G, Coakley FV, D'Amico AV, Higano CS, Iversen P, Kattan M, Nanus DM, Nelson JB, Oh WK, Roach M, Sellers WR, Smith MR, McMann MC, Kantoff PW. · Department of Urology, University of California School of Medicine, San Francisco 94115-1711, USA. · J Urol. · Pubmed #14610403 No free full text.

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D'Amico AV. · Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. · Urology. · Pubmed #12231043 No free full text.

Abstract: Patients with locally advanced prostate cancer (TNM clinical stage T3, T4) who were treated using external-beam radiotherapy (EBRT) and 3 years of androgen deprivation therapy (ADT) were compared with patients treated with EBRT alone and were shown to have a survival benefit. Studies that address the same question for patients with clinically localized disease (stage T1, T2) have been completed and are awaiting follow-up study. A rate of decrease in the serum hemoglobin level of > or =1 g/dL during the first month of neoadjuvant ADT predicted for a significantly worse disease-free survival outcome, as defined by the prostate-specific antigen, for patients with intermediate- and high-risk clinically localized disease who were undergoing EBRT and ADT. Validation of this predictive factor by others is needed.

D'Amico AV. · Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. · Oncology (Williston Park). · Pubmed #11548976 No free full text.

Abstract: The goal of identifying a set of pretreatment risk-stratifying factors for patients with localized prostate cancer is to be able to individualize treatment and optimize patient selection for clinical trials. Low-risk patients are most likely to remain disease-free following local therapy, whereas high-risk patients are not. By identifying a high-risk group in which approximately two-thirds of the patients fail biochemically within 10 years following local therapy, the ability to detect a difference in outcome as a result of additional therapy (if any difference exists) is maximized. Specifically, small improvements in outcome associated with the use of novel therapies can be measured more quickly in the high-risk population because of the intrinsically higher failure and progression rates. Therefore, novel therapies should be studied first in high-risk populations using a prospective randomized trial design (ie, local therapy with or without novel therapy). If efficacy is established in the high-risk cohort, then testing could be considered in the low-risk population. This review will demonstrate the ability to risk stratify more than 90% of all patients with clinically localized prostate cancer into low- or high-risk groups for biochemical progression following local therapy using four readily available pretreatment clinical parameters.

D'Amico AV, Halabi S, Vollmer R, Loffredo M, McMahon E, Sanford B, Archer L, Vogelzang NJ, Small EJ, Kantoff PW, Anonymous00198. · Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. · Urology. · Pubmed #18291508 No free full text.

Abstract: OBJECTIVES: It has been hypothesized that abnormal p53 protein expression is associated with a worse prognosis after radiation (RT) and androgen suppression therapy (AST). This hypothesis was prospectively tested. METHODS: Between May 1997 and April 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered on a study evaluating whether the endorectal magnetic resonance imaging (eMRI)-defined change in tumor volume (TV) during neoadjuvant (n) AST was associated with prostate-specific antigen (PSA) outcome. Of these, 141 had sufficient tissue to perform immunohistochemical detection of the p53 protein expression status and 113 had complete eMRI information. Multivariable Cox regression analysis was used to assess whether p53 protein expression status predicted time to PSA failure adjusting for known prognostic factors. RESULTS: After a median follow-up of 6.9 years and adjusting for PSA level, Gleason score, clinical stage, and eMRI-defined TV change during nAST, men with abnormal compared with normal p53 expression were at increased risk of PSA failure (hazard ratio [HR]: 2.8; 95% confidence interval [CI]: 1.3-5.9; P = 0.008 for the 141; HR: 2.4; 95% CI: 1.1-5.4; P = 0.03 for the 113). Adjusted estimates of PSA failure were significantly higher (P = 0.03) in men with abnormal compared with normal p53 expression. At 5 years, these respective estimates were 33% and 18%. CONCLUSIONS: Maximizing local control and randomized trials evaluating the impact on survival of adding novel agents to maximal local therapy are warranted in men whose prostate cancer demonstrates abnormal p53 expression.

D'Amico AV, Halabi S, Tempany C, Titelbaum D, Philips GK, Loffredo M, McMahon E, Sanford B, Vogelzang NJ, Small EJ, Anonymous00001. · Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, MA 02215, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18037582 No free full text.

Abstract: PURPOSE: We prospectively determined whether the change in tumor volume (TV) during 2 months of neoadjuvant androgen suppression therapy (nAST) measured using conventional 1.5 Tesla endorectal magnetic resonance imaging (eMRI) was associated with the risk of recurrence after radiation (RT) and 6 months of AST. PATIENTS AND METHODS: Between 1997 and 2001, 180 men with clinical stage T1c-T3cN0M0 adenocarcinoma of the prostate were registered. Fifteen were found to be ineligible and the institutional MR radiologist could not assess the TV in 32, leaving 133 for analysis. Multivariable Cox regression analysis was used to assess whether a significant association existed between eMRI-defined TV progression during nAST and time to recurrence adjusting for prostate-specific antigen (PSA) level, Gleason score (8 to 10 or 7 vs. 6 or less) and stage (T3 vs. T1-2). RESULTS: After a median follow up of 6.7 years and adjusting for known prognostic factors, there was a significant increase in the risk of PSA failure (HR, 2.3 [95% CI, 1.1-4.5; p = 0.025) in men with eMRI-defined TV progression during nAST. Specifically, adjusted estimates of PSA failure were significantly higher (p = 0.032) in men with, compared with men without, eMRI-defined TV progression reaching 38% vs. 19%, respectively, by 5 years. CONCLUSION: Eradicating intraprostatic hormone refractory prostate cancer (HRPC) by maximizing local control and randomized trials assessing whether survival is improved when agents active against HRPC are combined with maximal local therapy are needed in men who progress based on eMRI during nAST.

Nguyen PL, Chen MH, D'Amico AV, Tempany CM, Steele GS, Albert M, Cormack RA, Carr-Locke DL, Bleday R, Suh WW. · Department of Radiation Oncology, Brigham and Women's Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts. · Cancer. · Pubmed #17701957 links to  free full text

Abstract: BACKGROUND: The authors prospectively evaluated the late gastrointestinal (GI) and genitourinary (GU) toxicity and prostate-specific antigen (PSA) control of magnetic resonance imaging (MRI)-guided brachytherapy used as salvage for radiation therapy (RT) failure. METHODS: From October 2000 to October 2005, 25 men with a rising PSA level and biopsy-proven, intraprostatic cancer at least 2 years after initial RT (external beam in 13 men and brachytherapy in 12 men) who had favorable clinical features (Gleason score < or =7, PSA < 10 ng/mL, negative pelvic and bone imaging studies), received MRI-guided salvage brachytherapy to a minimum peripheral dose of 137 gray on a phase 1/2 protocol. Estimates of toxicity and cancer control were calculated using the Kaplan-Meier method. RESULTS: The median follow-up was 47 months. The 4-year estimate of grade 3 or 4 GI or GU toxicity was 30%, and 13% of patients required a colostomy and/or urostomy to repair a fistula. An interval < 4.5 years between RT courses was associated with both outcomes with a hazard ratio of 12 (95% confidence interval [95% CI], 1.4-100; P = .02) for grade 3 or 4 toxicity and 25 (95% CI, 1.1-529; P = .04) for colostomy and/or urostomy. PSA control (nadir +2 definition) was 70% at 4 years. CONCLUSIONS: The current results indicated that MRI-guided salvage brachytherapy in men who are selected based on presenting characteristics and post-failure PSA kinetics can achieve high PSA control rates, although complications requiring surgical intervention may occur in 10% to 15% of patients. Prospective randomized studies are needed to characterize the relative cancer control and toxicity after all forms of salvage local therapy.