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Video: Combination of mpMRI and TTMB of the prostate to identify candidates for hemi-ablative FT

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Combination of multi-parametric magnetic resonance imaging (mp-MRI) and transperineal template-guided mapping biopsy (TTMB) of the prostate to identify candidates for hemi-ablative focal therapy

Minh Tran*†‡, James Thompson*†§, Maret Bohm†, Marley Pulbrook†, Daniel Moses¶, Ron Shnier**, Phillip Brenner*†§, Warick Delprado††, Anne-Maree Haynes†, Richard Savdie§ and Phillip D. Stricker*†§

 

*St Vincent’s Prostate Cancer Centre, †Garvan Institute of Medical Research & The Kinghorn Cancer Centre, Darlinghurst, ‡School of Medicine, University of Sydney, §School of Medicine, University of New South Wales, Sydney, Spectrum Medical Imaging , **Southern Radiology, Randwick, and†† Douglass Hanly Moir Pathology, Darlinghurst, NSW, Australia

 

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OBJECTIVE

To evaluate the accuracy of combined multiparametric magnetic resonance imaging (mpMRI) and transperineal template-guided mapping biopsy (TTMB) for identifying lobes with significant prostate cancer (PCa) for the application of hemi-ablative focal therapy (FT).

PATIENTS AND METHODS

From January 2012 to January 2014, 89 consecutive patients, aged ≥40 years, with a PSA level ≤15 ng/mL, underwent in sequential order: mpMRI, TTMB and radical prostatectomy (RP) at a single centre. Analysis was performed on 50 patients who met consensus guidelines for FT. Lobes were stratified into lobes with significant cancer (LSC), lobes with insignificant cancer and lobes with no cancer. Using histopathology at RP, the predictive performance of combined mpMRI + TTMB in identifying LSC was evaluated.

RESULTS

The sensitivity, specificity and positive predictive value for mpMRI + TTMB for LSC were 97, 61 and 83%, respectively. The negative predictive value (NPV), the primary variable of interest, for mpMRI + TTMB for LSC was 91%. Of the 50 patients, 21 had significant unilateral disease on mpMRI + TTMB. Two of these 21 patients had significant bilateral disease on RP not identified on mpMRI + TTMB.

CONCLUSIONS

In the selection of candidates for FT, a combination of mpMRI and TTMB provides a high NPV in the detection of LSC.

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Video: How Can We Improve Surgical Outcomes?

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Recourse to radical prostatectomy and associated short-term outcomes in Italy: a country-wide study over the last decade

Giacomo Novara, Vincenzo Ficarra*, Filiberto Zattoni and Ugo Fedeli†

 

Department of Surgery, Oncology, and Gastroenterology, Urology Clinic, University of Padova, Padova, *Department of Experimental and Clinical Medical Sciences, Urologic Clinic, University of Udine, Udine, and †Epidemiological Department, Veneto Region, Italy

 

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OBJECTIVE

To estimate time trends in the recourse to radical prostatectomy (RP) and associated short-term outcomes after RP in Italy, as population-based data on RP adoption and outcomes are available mainly from Northern America and Northern Europe.

PATIENTS AND METHODS

All RPs for prostate cancer performed between 2001 and 2010 were extracted from the Italian national archive of hospital discharge records. Age-specific and age-standardised RP rates were computed. The effect of procedural volume on in-hospital mortality, complications, and length of stay (LOS) was estimated by multilevel regression models.

RESULTS

In all, 144 432 RPs were analysed. Country-wide RP rates increased between 2001 and 2004, and thereafter remained stable, with large differences between geographical areas. The mean hospital volume increased in the first study years, without centralisation but due to increasing RP numbers at the population level. The median LOS declined from 10 to 8 days over the study period (mean from 11.7 to 9.2 days). In-hospital mortality declined from 0.16% in 2001 to 0.07% in 2010. In-hospital mortality, LOS, and the prevalence of complications increased with age, and decreased with year of surgery. Compared with very low-volume hospitals, procedures performed in high-volume hospitals were associated with decreased in-hospital mortality, in-hospital complications, and LOS.

CONCLUSIONS

The study adds evidence on rapidly changing trends in RP rates in Italy, on improving in-hospital outcomes, and on their association with procedural volume.

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Video: Penile lengthening and widening without grafting according to a modified ‘sliding’ technique

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Penile lengthening and widening without grafting according to a modified ‘sliding’ technique

Paulo H. Egydio and Franklin E. Kuehhas*

 

Centre for Peyronie’s Disease Reconstruction, Sao Paulo, Brazil, and *London Andrology Institute, Suite 7 Exhibition House, Addison Bridge Place, London, UK

 

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OBJECTIVE

To present the feasibility and safety of penile length and girth restoration based on a modified ‘sliding’ technique for patients with severe erectile dysfunction (ED) and significant penile shortening, with or without Peyronie’s disease (PD).

PATIENTS AND METHODS

Between January 2013 and January 2014, 143 patients underwent our modified ‘sliding’ technique for penile length and girth restoration and concomitant penile prosthesis implantation. It is based on three key elements: (i) the sliding manoeuvre for penile length restoration; (ii) potential complementary longitudinal ventral and/or dorsal tunical incisions for girth restoration; and (iii) closure of the newly created rectangular bow-shaped tunical defects with Buck’s fascia only.

RESULTS

In all, 143 patients underwent the procedure. The causes of penile shortening and narrowing were: PD in 53.8%; severe ED with unsuccessful intracavernosal injection therapy in 21%; post-radical prostatectomy 14.7%; androgen-deprivation therapy, with or without brachytherapy or external radiotherapy, for prostate cancer in 7%; post-penile fracture in 2.1%; post-redo-hypospadias repair in 0.7%; and post-priapism in 0.7%. In patients with ED and PD, the mean (range) deviation of the penile axis was 45 (0‒100)°. The mean (range) subjective penile shortening reported by patients was 3.4 (1‒7) cm and shaft constriction was present in 53.8%. Malleable penile prostheses were used in 133 patients and inflatable penile prostheses were inserted in 10 patients. The median (range) follow-up was 9.7 (6‒18) months. The mean (range) penile length gain was 3.1 (2‒7) cm. No penile prosthesis infection caused device explantation. The average International Index of Erectile Function (IIEF) score increased from 24 points at baseline to 60 points at the 6-month follow-up.

CONCLUSION

Penile length and girth restoration based on our modified sliding technique is a safe and effective procedure. The elimination of grafting saves operative time and, consequently, decreases the infection risk and costs associated with surgery.

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Video: Comparison of systematic transrectal biopsy to transperineal MRI/(US)-fusion biopsy for the diagnosis of prostate cancer

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Comparison of systematic transrectal biopsy to transperineal MRI/ultrasound-fusion biopsy for the diagnosis of prostate cancer

Angelika Borkowetz, Ivan Platzek*, Marieta Toma†, Michael Laniado*, Gustavo Baretton†, Michael Froehner, Rainer Koch‡, Manfred Wirth and Stefan Zastrow

 

Department of Urology, *Department of Radiology and Interventional Radiology, †Department of Pathology, and ‡Institution of Medical Statistics and Epidemiology, Technische Universitat, Dresden, Germany

 

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OBJECTIVES

To compare targeted, transperineal magnetic resonance imaging (MRI)/ultrasound (US)-fusion biopsy to systematic transrectal biopsy in patients with previous negative or first prostate biopsy and to evaluate the gain in diagnostic information with systematic biopsies in addition to targeted MRI/US-fusion biopsies.

PATIENTS AND METHODS

In all, 263 consecutive patients with suspicion of prostate cancer were investigated. All patients were evaluated by 3-T multiparametric MRI (mpMRI) applying the European Society of Urogenital Radiology criteria. All patients underwent MRI/US-fusion biopsy transperineally (mean nine cores) and additionally a systematic transrectal biopsy (mean 12 cores).

RESULTS

In all, 195 patients underwent repeat biopsy and 68 patients underwent first biopsy. The median age was 66 years, median PSA level was 8.3 ng/mL and median prostate volume was 50 mL. Overall, the prostate cancer detection rate was 52% (137/263). MRI/US-fusion biopsy detected significantly more cancer than systematic prostate biopsy (44% [116/263] vs 35% [91/263]; P = 0.002). In repeat biopsy, the detection rate was 44% (85/195) in targeted and 32% (62/195) in systematic biopsy (P = 0.002). In first biopsy, the detection rate was 46% (31/68) in targeted and 43% (29/68) in systematic biopsy (P = 0.527). In all, 80% (110/137) of biopsy confirmed prostate cancers were clinically significant. For the upgrading of Gleason score, 44% (32/72) more clinically significant prostate cancer was detected by using additional targeted biopsy than by systematic biopsy alone. Conversely, 12% (10/94) more clinically significant cancer was found by systematic biopsy additionally to targeted biopsy.

CONCLUSIONS

MRI/US-fusion biopsy was associated with a higher detection rate of clinically significant prostate cancer while taking fewer cores, especially in patients with prior negative biopsy. Due to a high portion of additional tumours with Gleason score ≥7 detected in addition to targeted biopsy, systematic biopsy should still be performed additionally to targeted biopsy.

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Video: Predicting pathological outcomes in patients undergoing RARP for high-risk prostate cancer: A Preoperative Nomogram

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Predicting Pathologic Outcomes in Patients Undergoing Robot-Assisted Radical Prostatectomy for High Risk Prostate Cancer:  A Preoperative Nomogram

Firas Abdollah, Dane E. Klett, Akshay Sood, Jesse D. Sammon, Daniel Pucheril, Deepansh Dalela, Mireya Diaz, James O. Peabody, Quoc-Dien Trinh* and Mani Menon

 

Vattikuti Urology Institute, Center for Outcomes Research Analytics and Evaluation, Henry Ford Health System, Detroit, MI, and *Division of Urologic Surgery/Center for Surgery and Public Health, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

 

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OBJECTIVE

To identify which high-risk patients with prostate cancer may harbour favourable pathological outcomes at radical prostatectomy (RP).

PATIENTS AND METHODS

We evaluated 810 patients with high-risk prostate cancer, defined as having one or more of the following: PSA level of >20 ng/mL, Gleason score ≥8, clinical stage ≥T2c. Patients underwent robot-assisted RP (RARP) with pelvic lymph node dissection, between 2003 and 2012, in one centre. Only 1.6% (13/810) of patients received any adjuvant treatment. Favourable pathological outcome was defined as specimen-confined disease (SCD; pT2–T3a, node negative, and negative surgical margins) at RARP-specimen. Logistic regression models were used to test the relationship among all available predicators and harbouring SCD. A logistic regression coefficient-based nomogram was constructed and internally validated using 200 bootstrap resamples. Kaplan–Meier method estimated biochemical recurrence (BCR)-free and cancer-specific mortality (CSM)-free survival rates, after stratification according to pathological disease status.

RESULTS

Overall, 55.2% patients harboured SCD at RARP. At multivariable analysis, PSA level, clinical stage, primary/secondary Gleason scores, and maximum percentage tumour quartiles were all independent predictors of SCD (all P < 0.04). A nomogram based on these variables showed 76% discrimination accuracy in predicting SCD, and very favourable calibration characteristics. Patients with SCD had significantly higher 8-year BCR- (72.7% vs 31.7%, P < 0.001) and CSM-free survival rates (100% vs 86.9%, P < 0.001) than patients with non-SCD.

CONCLUSIONS

We developed a novel nomogram predicting SCD at RARP. Patients with SCD achieved favourable long-term BCR- and CSM-free survival rates after RARP. The nomogram may be used to support clinical decision-making, and aid in selection of patients with high-risk prostate cancer most likely to benefit from RARP.

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Video: Postoperative RT for patients at high-risk of recurrence after RP: does timing matter?

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Postoperative radiation therapy for patients at high-risk of recurrence after radical prostatectomy: does timing matter?

Charles C. Hsu*†, Alan T. Paciorek‡, Matthew R. Cooperberg‡, Mack Roach III*, I-Chow J. Hsu* and Peter R. Carroll‡

 

*Department of Radiation Oncology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, †Department of Radiation Oncology, College of Medicine, University of Arizona, Tucson, AZ, and ‡Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA

 

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OBJECTIVE

To evaluate among radical prostatectomy (RP) patients at high-risk of recurrence whether the timing of postoperative radiation therapy (RT) (adjuvant, early salvage with detectable post-RP prostate-specific antigen [PSA], or ‘late’ salvage with a PSA level of >1.0 ng/mL) is significantly associated with overall survival (OS), prostate-cancer specific survival or metastasis-free survival, in a longitudinal cohort.

PATIENTS AND METHODS

Of 6 176 RP patients in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), 305 patients with high-risk pathological features (margin positivity, Gleason score 8–10, or pT3–4) who underwent postoperative RT were examined, either in the adjuvant (≤6 months after RP with undetectable PSA levels, 76 patients) or salvage setting (>6 months after RP or pre-RT PSA level of >0.1 ng/mL, 229 patients). Early (PSA level of ≤1.0 ng/mL, 180 patients) or late salvage RT (PSA level >1.0 ng/mL, 49 patients) was based on post-RP, pre-RT PSA level. Multivariable Cox regression examined associations with all-cause mortality and prostate cancer-specific mortality and/or metastases (PCSMM).

RESULTS

After a median of 74 months after RP, 65 men had died (with 37 events of PCSMM). Adjuvant and salvage RT patients had comparable high-risk features. Compared with adjuvant, salvage RT (early or late) had an increased association with all-cause mortality (hazard ratio [HR] 2.7, P = 0.018) and with PCSMM (HR 4.0, P = 0.015). PCSMM-free survival differed by further stratification of timing, with 10-year estimates of 88%, 84%, and 71% for adjuvant, early salvage, and late salvage RT, respectively (P = 0.026). For PCSMM-free survival and OS, compared with adjuvant RT, late salvage RT had statistically significantly increased risk; however, early salvage RT did not.

CONCLUSION

This analysis suggests that patients who underwent early salvage RT with PSA levels of <1.0 ng/mL may have comparable metastasis-free survival and OS compared with adjuvant RT; however, late salvage RT with a PSA level of >1.0 ng/mL is associated with worse clinical outcomes.

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Video: The severity of LUTS is associated with an increase of Framingham CVD risk score

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Increase of Framingham cardiovascular disease risk score is associated with severity of lower urinary tract symptoms

Giorgio I. Russo, Tommaso Castelli, Salvatore Privitera, Eugenia Fragala, Vincenzo Favilla, Giulio Reale, Daniele Urzı, Sandro La Vignera*, Rosita A. Condorelli*, Aldo E. Calogero*, Sebastiano Cimino and Giuseppe Morgia

 

Department of Urology, and *Department of Medical and Paediatric Sciences, Section of Endocrinology, Andrology and Internal Medicine, University of Catania, Catania, Italy

 

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OBJECTIVE

To determine the relationship between lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) and 10-year risk of cardiovascular disease (CVD) assessed by the Framingham CVD risk score in a cohort of patients without previous episodes of stroke and/or acute myocardial infarction.

PATIENTS AND METHODS

From September 2010 to September 2014, 336 consecutive patients with BPH-related LUTS were prospectively enrolled. The general 10-year Framingham CVD risk score, expressed as percentage and assessing the risk of atherosclerotic CVD events, was calculated for each patient. Individuals with low risk had ≤10% CVD risk at 10 years, with intermediate risk 10–20% and with high risk ≥20%. Logistic regression analyses were used to identify variables for predicting a Framingham CVD risk score of ≥10% and moderate–severe LUTS (International Prostate Symptom Score [IPSS] ≥8), adjusted for confounding factors.

RESULTS

As category of Framingham CVD risk score increased, we observed higher IPSS (18.0 vs 18.50 vs 19.0; P < 0.05), high IPSS–voiding (6.0 vs 9.0 vs 9.5; P < 0.05) and worse sexual function. Prostate volume significantly increased in those with intermediate- vs low-risk scores (54.5 vs 44.1 mL; P < 0.05). Multivariate logistic regression analysis showed that intermediate- [odds ratio (OR) 8.65; P < 0.01) and high-risk scores (OR 1.79; P < 0.05) were independently associated with moderate–severe LUTS. At age-adjusted logistic regression analysis, moderate–severe LUTS was independently associated with Framingham CVD risk score of ≥10% (OR 5.91; P < 0.05).

CONCLUSION

Our cross-sectional study in a cohort of patients with LUTS–BPH showed an increase of more than five-fold of having a Framingham CVD risk score of ≥10% in men with moderate–severe LUTS.

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Video: Significance of time interval between first and second TUR on recurrence and progression rates in BCG-treated NMIBC

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Significance of time interval between first and second transurethral resection on recurrence and progression rates in patients with high risk non muscle invasive bladder cancer treated with maintenance intravesical Bacillus Calmette-Guerin

 

Sumer Baltacı, Murat Bozlu*, Asıf Yıldırım†, Mehmet Ilker Gokce, İlker Tinay‡, Guven Aslan§, Cavit Can, Levent Turkeri‡,Ugur Kuyumcuoglu** and Aydın Mungan††

 

Department of Urology, Ankara University School of Medicine, Ankara , *Department of Urology, University of Mersin School of Medicine, Mersin,†Department of Urology, Istanbul Medeniyet University School of Medicine, ‡Department of Urology, Marmara University School of Medicine, Istanbul, §Department of Urology, Dokuz Eylul University School of Medicine Inciralti, Izmir, Department of Urology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, **Department of Urology, Trakya University School of Medicine, Edirne, and ††Department of Urology, Bulent Ecevit University School of Medicine, Zonguldak, Turkey

 

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OBJECTIVES

To evaluate the effect of the interval between the initial and second transurethral resection (TUR) on the outcome of patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with maintenance intravesical Bacillus Calmette-Guérin (BCG) therapy.

PATIENTS AND METHODS

We reviewed the data of patients from 10 centres treated for high-risk NMIBC between 2005 and 2012. Patients without a diagnosis of muscle-invasive cancer on second TUR performed ≤90 days after a complete first TUR, and received at least 1 year of maintenance BCG were included in this study. The interval between first and second TUR in addition to other parameters were recorded. Multivariate logistic regression analysis was used to identify predictors of recurrence and progression.

RESULTS

In all, 242 patients were included. The mean (sd, range) follow-up was 29.4 (22.2, 12–96) months. The 3-year recurrence- and progression-free survival rates of patients who underwent second TUR between 14 and 42 days and 43–90 days were 73.6% vs 46.2% (P < 0.001) and 89.1% vs 79.1% (P = 0.006), respectively. On multivariate analysis, the interval to second TUR was found to be a predictor of both recurrence [odds ratio (OR) 3.598, 95% confidence interval (CI) 1.885–8.137; P = 0.001] and progression (OR 2.144, 95% CI 1.447–5.137; P = 0.003).

CONCLUSIONS

The interval between first and second TUR should be ≤42 days in order to attain lower recurrence and progression rates. To our knowledge, this is the first study demonstrating the effect of the interval between first and second TUR on patient outcomes.

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Video: Complications following AUS placement after RP and radiotherapy

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Complications following artificial urinary sphincter placement after radical prostatectomy and radiotherapy: a meta-analysis

Anthony S. Bates1,*, Richard M. Martin2 and Tim R. Terry1

1Department of Urology, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, UK 2School of Social and Community Medicine, University of Bristol, Bristol, UK

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Objective

To conduct a systematic review and meta-analysis of artificial urinary sphincter (AUS) placement after radical prostatectomy (RP) and external beam radiotherapy (EBRT).

Patients and Methods

There were 1 886 patients available for analysis of surgical revision outcomes and 949 for persistent urinary incontinence (UI) outcomes from 15 and 11 studies, respectively. The mean age (sd) was 66.9 (1.4) years and the number of patients per study was 126.6 (41.7). The mean (sd, range) follow-up was 36.7 (3.9, 18–68) months. A systematic database search was conducted using keywords, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Published series of AUS implantations were retrieved, according to the inclusion criteria. The Newcastle–Ottawa Score was used to ascertain the quality of evidence for each study. Surgical results from each case series were extracted. Data were analysed using CMA® statistical software.

Results

AUS revision was higher in RP + EBRT vs RP alone, with a random effects risk ratio of 1.56 (95% confidence interval [CI] 1.02–2.72; P < 0.050; I2 = 82.0%) and a risk difference of 16.0% (95% CI 2.05–36.01; P < 0.080). Infection/erosion contributed to the majority of surgical revision risk compared with urethral atrophy (P = 0.020). Persistent UI after implantation was greater in patients treated with EBRT (P < 0.001).

Conclusions

Men receiving RP + EBRT appear at increased risk of infection/erosion and urethral atrophy, resulting in a greater risk of surgical revision compared with RP alone. Persistent UI is more common with RP + EBRT.

 

Video: A phase I study of TRC105 anti-CD105 (endoglin) antibody in mCRPC

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A phase I study of TRC105 anti-CD105 (endoglin) antibody in metastatic castration-resistant prostate cancer

Fatima H. Karzai, Andrea B. Apolo, Liang Cao, Ravi A. Madan, David E. Adelberg, Howard Parnes, David G. McLeod, Nancy Harold, Cody Peer, Yunkai Yu, Yusuke Tomita,,Min-Jung Lee, Sunmin Lee, Jane B. Trepel, James L. Gulley, William D. Figg and William L. Dahut

 

Medical Oncology Service, National Cancer Institute, Bethesda, MD, USA

 

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OBJECTIVE

TRC105 is a chimeric immunoglobulin G1 monoclonal antibody that binds endoglin (CD105). This phase I open-label study evaluated the safety, pharmacokinetics and pharmacodynamics of TRC105 in patients with metastatic castration-resistant prostate cancer (mCRPC).

PATIENTS AND METHODS

Patients with mCRPC received escalating doses of i.v. TRC105 until unacceptable toxicity or disease progression, up to a predetermined dose level, using a standard 3 + 3 phase I design.

RESULTS

A total of 20 patients were treated. The top dose level studied, 20 mg/kg every 2 weeks, was the maximum tolerated dose. Common adverse effects included infusion-related reaction (90%), low grade headache (67%), anaemia (48%), epistaxis (43%) and fever (43%). Ten patients had stable disease on study and eight patients had declines in prostate specific antigen (PSA). Significant plasma CD105 reduction was observed at the higher dose levels. In an exploratory analysis, vascular endothelial growth factor (VEGF) was increased after treatment with TRC105 and VEGF levels were associated with CD105 reduction.

CONCLUSION

TRC105 was tolerated at 20 mg/kg every other week with a safety profile distinct from that of VEGF inhibitors. A significant induction of plasma VEGF was associated with CD105 reduction, suggesting anti-angiogenic activity of TRC105. An exploratory analysis showed a tentative correlation between the reduction of CD105 and a decrease in PSA velocity, suggestive of potential activity of TRC105 in the patients with mCRPC. The data from this exploratory analysis suggest that rising VEGF level is a possible compensatory mechanism for TRC105-induced anti-angiogenic activity.

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