Prostatic Neoplasms: D'Amico A

Arlen PM, Bianco F, Dahut WL, D'Amico A, Figg WD, Freedland SJ, Gulley JL, Kantoff PW, Kattan MW, Lee A, Regan MM, Sartor O, Anonymous00032. · Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. · J Urol. · Pubmed #18423743 links to  free full text

Abstract: PURPOSE: Prostate specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells. Prostate specific antigen doubling time, or the change in prostate specific antigen over time, has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer. It is important to agree on definitions and values for the calculation of prostate specific antigen doubling time, and to develop a common approach to outcome analysis and reporting. MATERIALS AND METHODS: In September 2006 a conference was held at the National Cancer Institute in Bethesda, Maryland to define these parameters and develop guidelines for their use. RESULTS: The Prostate Specific Antigen Working Group defined criteria regarding prostate specific antigen doubling time including the calculation of prostate specific antigen doubling time, evidence to support prostate specific antigen doubling time as a predictive factor in the setting of biochemical recurrence and the use of prostate specific antigen doubling time as a stratification factor in clinical trials. CONCLUSIONS: We propose that investigators calculate prostate specific antigen doubling time before enrolling patients in clinical studies and calculate it as an additional measurement of therapeutic activity. We believe we have developed practical guidelines for the calculation of prostate specific antigen doubling time and its use as a measurement of prognosis and outcome. Furthermore, the use of common standards for prostate specific antigen doubling time in clinical trials is important as we determine which treatments should progress to randomized trials in which "hard" end points such as survival will be used.

Mohler J, Babaian RJ, Bahnson RR, Boston B, D'Amico A, Eastham JA, Hauke RJ, Huben RP, Kantoff P, Kawachi M, Kuettel M, Lange PH, Logothetis C, MacVicar G, Pollack A, Pow-Sang JM, Roach M, Sandler H, Shrieve D, Srinivas S, Twardowski P, Urban DA, Walsh PC, Anonymous00332. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #17692170 No free full text.

This publication has no abstract.

D'Amico A. · Genitourinary Radiation Oncology, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. · BJU Int. · Pubmed #17229162 No free full text.

Abstract: Prostate-specific antigen doubling time (PSA-DT) after surgery or radiotherapy (RT) is known to be a predictive factor for death from prostate cancer (prostate cancer-specific mortality, PCSM). An analysis of two multi-institutional databases, including 8669 men with prostate cancer treated with surgery or RT, found that a PSA-DT of <3 months, and the specific value of the PSA-DT when > or = 3 months, appeared to be surrogate endpoints for PCSM after surgery or RT. While many PSA failures occur after local therapy for localized prostate cancer, few of these patients go on to die from their disease, so it is important to identify other factors associated with PCSM, so that the subgroup of high-risk patients can be identified. An analysis was undertaken to determine whether patients at risk of PCSM could be identified using information available at diagnosis. The results showed that risk factors for PCSM were a PSA velocity of >2.0 ng/mL/year, a Gleason score of 8-10 and an increasing PSA level. However, the most important risk factor that had an impact on both PCSM and all-cause mortality was a PSA velocity of >2.0 ng/mL/year. PSA kinetics are being increasingly used in the setting of rising PSA levels after radical prostatectomy or RT, and several studies showed that the rate of increase in PSA level at the time of recurrence is closely associated with time to cancer death. A PSA-DT of <3 months is associated with a poor prognosis, and represents 15-20% of PSA failures in the general population and 6-7% of PSA failures in a screened population, such as those included in clinical trials. Better risk-assessment models are needed to help to identify at an early stage men who are at high risk of prostate cancer death and those who are at low risk, so that each subgroup can receive the most appropriate therapy for their disease.

Small EJ, Halabi S, Kantoff P, D'Amico A, Stadler W, Kelley WK, Mohler J, Bajorin D, Vogelzang NJ. · University of California/San Francisco, San Francisco, California, USA. · Clin Cancer Res. · Pubmed #16740791 links to  free full text

Abstract: The Cancer and Leukemia Group B Genitourinary (GU) Committee has developed a multidisciplinary approach to treatment of GU cancer and has integrated correlative science research into the major research themes of the GU Committee. In localized prostate cancer, trials have evaluated novel approaches in radiation therapy. For patients with recurrence after local therapy, a trial evaluating local recurrence with salvage prostatectomy and a study of systemic therapy with "peripheral androgen blockade" were undertaken. Major contributions have been made in developing and testing therapeutics for advanced, androgen-independent prostate cancer (ketoconazole, suramin, estramustine/docetaxel, and docetaxel/bevacizumab), and in developing predictive markers and algorithms to assess prognosis in these patients. Contributions in kidney cancer have included the development of novel trial methodology, such as the randomized discontinuation trial design, and the testing of antiangiogenics. In addition to these areas, future work of the committee will include further development of therapy for earlier-stage prostate cancer patients and bladder cancer patients.

Cooperberg MR, Small EJ, D'Amico A, Carroll PR. · Department of Urology, UCSF/Mt Zion Comprehensive, Cancer Center, University of California, San Francisco, CA 94115-1711, USA. · Minerva Urol Nefrol. · Pubmed #14765015 No free full text.

Abstract: Androgen deprivation therapy (ADT) plays a central role in the management of prostate cancer. ADT is the mainstay of treatment for metastatic disease; the most common method is gonadal suppression via luteinizing hormone release hormone (LH) agonists, with or without antiandrogens. Antiandrogen monotherapy remains investigational, as is the appropriate role of 5alphareductase inhibition for prostate cancer. Intermittent ADT offers the promise of improved quality of life and reduced cost without a decrease found to date in oncologic efficacy. A growing menu of options exists for secondary androgen deprivation after disease progression on primary therapy: these include high-dose antiandrogens, estrogens, and adrenal androgen suppressants. ADT is being used with increasing frequency as primary monotherapy in patients with localized disease, but only small, nonrandomized studies of highly selected patients have been reported to date. Neoadjuvant ADT (NADT) has been demonstrated in prospective, multi-institutional trials to improve outcomes for patients with high-risk or locally advanced disease undergoing external-beam radiotherapy. Trials for patients with lower-risk, localized disease are still ongoing. Neoadjuvant therapy does not improve outcomes for patients with localized disease opting for radical prostatectomy (RP) and has not been well studied in association with brachytherapy. The side effects of ADT can be managed increasingly successfully; in particular, the introduction of zoledronate may reduce the impact of ADT-associated osteoporosis. Finally, contemporary practice pattern data suggest that use of ADT is increasing across patient risk groups, both in contexts where such therapy is well supported by current evidence and in others where it is not.

Vira MA, Guzzo T, Heitjan DF, Tomaszewski JE, D'Amico A, Wein AJ, Malkowicz SB. · The Smith Institute for Urology, North Shore Long Island Jewish Health System, New Hyde Park, NY 11040, USA. · BJU Int. · Pubmed #18419697 No free full text.

Abstract: OBJECTIVE: To evaluate whether specific preoperative variables might better predict the concordance between biopsy and radical prostatectomy (RP) Gleason grade, and to assess the effect of the biopsy Gleason score (bGS) when controlling for the pathological GS (pGS) on clinical outcomes in patients undergoing RP. PATIENTS AND METHODS: Between 1989 and 1998, 1088 men had RP at our institution, with a median follow-up of 56 months. To evaluate the independent effect of bGS within categories of pGS, we stratified the sample by pGS (three categories; <or=6, 7, 8-10). Within each stratum we constructed Kaplan-Meier plots of recurrence-free survival by bGS (in the same three categories), assessing the significance of the differences among the three curves by the log-rank test. RESULTS: Overall, only 41.1% of patients had exactly concordant findings between bGS and pGS; concordance rates did not differ significantly when stratified by preoperative variables. On multivariate analysis, a change in the pGS compared with the bGS had a significant, independent effect on recurrence rates, specifically a 15% change in risk for a one-unit change in GS (P = 0.021). CONCLUSIONS: There was only modest agreement between the bGS and the pGS; the bGS continued to have independent prognostic influence after RP and assignment of the pGS.

Dickhaus CF, Burghart C, Tempany C, D'Amico A, Haker S, Kikinis R, Woern H. · Surgical Planning Laboratory, Brigham and Women's Hospital Harvard Medical School, Boston, MA, USA. · Stud Health Technol Inform. · Pubmed #15544246 No free full text.

Abstract: We demonstrate that classical Business Process Reengineering (BPR) methods can be successfully applied to Computer Aided Surgery while increasing safety and efficiency of the overall procedure through an integrated Workflow Management System. Computer guided Prostate Brachytherapy, as a sophisticated treatment by an interdisciplinary team, is perfectly suited to apply our method. Detailed suggestions for improvement of the whole procedure could be derived by our modified BPR method.

Hirose M, Bharatha A, Hata N, Zou KH, Warfield SK, Cormack RA, D'Amico A, Kikinis R, Jolesz FA, Tempany CM. · Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. · Acad Radiol. · Pubmed #12186439 No free full text.

Abstract: RATIONALE AND OBJECTIVES: The authors performed this study to document the deformations that occur between pretreatment magnetic resonance (MR) imaging and intraoperative MR imaging during brachytherapy. MATERIALS AND METHODS: MR images obtained at 1.5 and 0.5 T in 10 patients with prostate cancer were analyzed for changes in the shape and substructure of the prostate. Three-dimensional models of the prostate were obtained. The authors measured anteroposterior dimension; total gland, peripheral zone, and central gland volumes; transverse dimension; and superoinferior height. RESULTS: Gland deformations were seen at visual inspection of the three-dimensional models. The anteroposterior dimension of the total gland, central gland, and peripheral zone increased from 1.5- to 0.5-T imaging (median dimension, 4.9, 1.5, and 1.8 mm, respectively), and the increase was greatest in the peripheral zone (P < .05, all comparisons). There was a decrease in the transverse dimension from 1.5- to 0.5-T imaging (median, 4.5 mm; P < .005). The total gland volume and the superoinferior height did not show a statistically significant change. CONCLUSION: There were significant deformations in the shape of the prostate, especially in the peripheral zone, between the two imaging studies. The likely causes of the shape change are differences in rectal filling (endorectal coil used in 1.5-T studies vs obturator in 0.5-T studies) and/or changes in patient position (supine vs lithotomy). These findings suggest that pretreatment images alone may not be reliable for accurate therapy planning. It may be useful to integrate pre-and intraoperative data.

Bharatha A, Hirose M, Hata N, Warfield SK, Ferrant M, Zou KH, Suarez-Santana E, Ruiz-Alzola J, D'Amico A, Cormack RA, Kikinis R, Jolesz FA, Tempany CM. · Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. · Med Phys. · Pubmed #11797960 No free full text.

Abstract: In this report we evaluate an image registration technique that can improve the information content of intraoperative image data by deformable matching of preoperative images. In this study, pretreatment 1.5 tesla (T) magnetic resonance (MR) images of the prostate are registered with 0.5 T intraoperative images. The method involves rigid and nonrigid registration using biomechanical finite element modeling. Preoperative 1.5 T MR imaging is conducted with the patient supine, using an endorectal coil, while intraoperatively, the patient is in the lithotomy position with a rectal obturator in place. We have previously observed that these changes in patient position and rectal filling produce a shape change in the prostate. The registration of 1.5 T preoperative images depicting the prostate substructure [namely central gland (CG) and peripheral zone (PZ)] to 0.5 T intraoperative MR images using this method can facilitate the segmentation of the substructure of the gland for radiation treatment planning. After creating and validating a dataset of manually segmented glands from images obtained in ten sequential MR-guided brachytherapy cases, we conducted a set of experiments to assess our hypothesis that the proposed registration system can significantly improve the quality of matching of the total gland (TG), CG, and PZ. The results showed that the method statistically-significantly improves the quality of match (compared to rigid registration), raising the Dice similarity coefficient (DSC) from prematched coefficients of 0.81, 0.78, and 0.59 for TG, CG, and PZ, respectively, to 0.94, 0.86, and 0.76. A point-based measure of registration agreement was also improved by the deformable registration. CG and PZ volumes are not changed by the registration, indicating that the method maintains the biomechanical topology of the prostate. Although this strategy was tested for MRI-guided brachytherapy, the preliminary results from these experiments suggest that it may be applied to other settings such as transrectal ultrasound-guided therapy, where the integration of preoperative MRI may have a significant impact upon treatment planning and guidance.

D'Amico A. · Department of Radiation Oncology, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA. · Urology. · Pubmed #11502455 No free full text.

Abstract: Increasingly, radiation therapists are using neoadjuvant and/or adjuvant androgen deprivation therapy (ADT) in higher-risk patients who are receiving radiation therapy with curative intent. Studies supporting this combination therapy have shown a benefit in patients with locally advanced disease based on the relatively short follow-up time to report, to date. The differing study designs, patient selection criteria, and regimens used in these studies are reviewed and compared, along with the reported outcomes. Trials currently underway will examine the efficacy of ADT (4 to 6 months in duration) in patients with clinically localized prostate cancer with >/=1 high-risk features.

Ficarra V, Righetti R, D'Amico A, Pilloni S, Balzarro M, Schiavone D, Malossini G, Mobilio G. · Department of Urology, University of Verona, Italy. · Urol Int. · Pubmed #11054029 No free full text.

Abstract: OBJECTIVE: To evaluate the general state of health and the psychological well-being in a group of 155 patients after surgery for urological malignant neoplasms. MATERIALS AND METHODS: Surgery was performed in 55 patients for renal cell carcinoma, in 54 for invasive bladder carcinoma, in 30 for adenocarcinoma of the prostate, and in 16 for squamous penile carcinoma. All patients were invited to self-compile the General Health Questionnaire (GHQ) - 12 items according to Goldberg and the Hospital Anxiety and Depression Scale. Results were compared with those in a group of patients who underwent retropubic prostatectomy for benign prostatic hyperplasia. RESULTS AND CONCLUSION: The general state of health was significantly more impaired in neoplastic patients than in the control group. Levels of anxiety were significantly higher but depression levels were similar in both groups. As far as the type of tumor is concerned, patients who underwent radical cystectomy for bladder carcinoma and those treated with partial penectomy for squamous penile carcinoma showed a significant impairment of the general state of health compared with controls. Higher levels of anxiety were observed in patients who underwent ileal conduit after radical cystectomy, in those treated with radical prostatectomy for prostate cancer and in those who underwent partial penectomy. Significantly higher levels of depression than in the control group were observed only in patients with ileal conduit.

D'Amico A, Cormack R, Kumar S, Tempany CM. · Joint Center for Radiation Therapy, Harvard Medical School, Boston, Massachusetts 02215, USA. · J Endourol. · Pubmed #10910153 No free full text.

Abstract: BACKGROUND AND PURPOSE: A real-time three-dimensional magnetic resonance imaging (MRI)-guided implant technique has been designed and implemented. This report summarizes the dosimetry achieved and the acute morbidity in the first patients. PATIENTS AND METHODS: To date, 43 patients with clinical stage T(1c)N(X)M(0) prostate cancer, serum prostate specific antigen <10 ng/mL, and biopsy Gleason score no higher than 3 + 4 have been treated. The procedure was performed using an open magnet, with axial T1-weighted and fast spin echo images. The prescribed minimum radiation dose to the peripheral zone was 160 Gy. The total activity implanted ranged from 18.8 to 47.5 mCi using 43 to 120 (median 80) (125)I seeds. Dosimetric analyses were performed intraoperatively in real time for the tumor, anterior rectal wall, and prostatic urethra. RESULTS: The percent of the clinical target volume receiving the prescription dose was 89% to 99% (median 96%). Using a conservative estimate of 164 Gy, no more than 9% of the urethral volume exceeded the tolerated dose. Using an estimated tolerated dose of 82 Gy, 30% to 100% (median 68%) of the anterior rectal wall volume was within the dose limit. Thirty-nine patients voided spontaneously within 3 hours of Foley catheter discontinuation, although four patients required recatheterization for a period. No patient reported gastrointestinal or sexual dysfunction during the first postoperative month. CONCLUSION: A real-time MR-guided technique can achieve a minimum of 89% coverage of the tumor volume while maintaining the prostatic urethra and most of the anterior rectal wall below tolerance levels. Acute morbidity was minimal. Further follow-up is needed to ascertain the impact on cancer control and quality of life.

Punglia RS, Kuntz KM, Catalona WJ, D'Amico A. · No affiliation provided · JAMA. · Pubmed #16333002 No free full text.

This publication has no abstract.