BERKELEY, CA (UroToday.com) - Through a special arrangement with the British Journal of Urology International (BJUI), UroToday is pleased to host the BJUI "Article of the Month."
June 2015: Clinical utility of 18F-fluorocholine positron-emission tomography/computed tomography (PET/CT) in biochemical relapse of prostate cancer after radical treatment: Results of a multicentre study
OBJECTIVE: This study evaluated the usefulness of 18F-fluorocholine PET/CT in restaging patients with a history of prostate adenocarcinoma who faced biochemical relapse after early radical treatment, and correlated the technique's disease detection rate with a set of variables and clinical and pathological parameters.
MATERIAL AND METHODS: This was a retrospective multicentre study which included 374 patients referred for choline PET/CT who had biochemical relapse. In the end, 233 patients who met the following inclusion criteria were analysed: diagnosis of prostate cancer; early radical treatment; biochemical relapse; main clinical and pathological variables; and clinical, pathological and imaging data needed to validate the results. Criteria used to validate the PET/CT: findings from other imaging techniques, clinical follow-up, treatment response and histological analysis. Different statistical tests were used depending on the distribution of the data to correlate the results of the choline PET/CT with qualitative (T, N, early prostatectomy vs. other treatments, hormone therapy concomitant to choline PET/CT) and quantitative (age, Gleason score, PSA levels at diagnosis, PSA nadir, PSA on the day of the choline PET/CT or trigger PSA and PSADT) variables. We analysed whether there were independent predictive factors associated with the positive PET/CT result. All statistical tests were considered two-sided and significant values where p< 0.05.
RESULTS: The choline PET/CT was positive in 111 of 233 patients (detection rate: 47.6%) and negative in 122 (52.4%). Disease locations: prostate or prostate bed in 26 patients (23.4%); regional and/or distant lymph nodes in 52 (46.8%); and metastatic bone disease in 33 (29.7%). Positive findings were validated by: results from other imaging techniques in 35 patients (15.0%); at least 6 months of clinical follow-up in 136 (58.4%); treatment response in 24 (10.3%); histological analysis of lesions in 17 (7.3%); and follow-up plus imaging results in 21 (9.0%). The statistical analysis of qualitative variables, corresponding to patients' clinical characteristics, and the positive/negative final PET/CT results revealed that only whether or not early treatment with radical prostatectomy was done was statistically significant (p< 0.001), with the number of positive results higher in patients who did not undergo a radical prostatectomy. Among the quantitative variables, Gleason score, trigger PSA and PSADT clearly differentiated the two patient groups (positive and negative choline PET/CT): p=0.010, p=0.001 and p=0.025, respectively. A Gleason score of < 5 or ≥8 clearly differentiated positive from negative PET. Trigger PSA: mean of 8 ngr/ml for positive PET/CT vs. 2.8 for negative PET/CT; PSADT: mean of 8 months for positive PSADT and 12.6 for negative PSADT. The optimal cut-off points were: 3 ngr/ml for trigger PSA and 6 months for PSADT (Youden index/ROC curve). Analysing these two variables together showed that PSADT was more conclusive in patients with lower PSA Trigger. Analysing variables by location showed that only PSADT was able to differentiate between those with disease confined to the prostate compared with the other two locations (lymph nodes and bone), with shorter PSADT in these two, which was statistically significant (p< 0.002). In the patient group with PSA of < 1.5 ngr/ml, 30.8% had the disease, 7% of whom had metastatic bone disease. In the multivariate logistic regression, the risks factors that were clearly independent for those with positive PET/CT were: PSA >3 ngr/ml; no early prostatectomy; and Gleason score of ≥8.
CONCLUSION: Our results support the usefulness of 18F-fluorocholine PET/CT in biochemical relapse of prostate cancer after radical treatment, with an overall disease detection rate close to 50%, and it can be recommended as first-line treatment. As mentioned above, besides PSA levels on the day of the PET/CT, there are other clinical and pathological variables to consider in order to screen patients properly and thus minimise the number of nodular lesions and increase the diagnostic accuracy of the exam.
Sonia Rodado-Marina, Mónica Coronado-Poggio, Ana María García-Vicente,* Jose Ramón García-Garzón,† Aurora Crespo de la Jara,‡ Antonio Maldonado-Suárez,§ and Antonio Rodríguez-Fernández¶
Department of Nuclear Medicine, La Paz Universitary Hospital and §Quirón Universitary Hospital, Madrid, *Department of Nuclear Medicine, Universitary Hospital, Ciudad Real, †CETIR Unitat PET Esplugues, Barcelona, ‡Department of Nuclear Medicine, Quirón Hospital, Torrevieja, and ¶Department of Nuclear Medicine, Virgen de las Nieves Universitary Hospital, Granada, Spain
May 2015: Transient receptor potential channel modulators as pharmacological treatments for lower urinary tract symptoms (LUTS): Myth or reality?
Transient receptor potential (TRP) channels belong to the most intensely pursued drug targets of the last decade. These ion channels are considered promising targets for the treatment of pain, hypersensitivity disorders and lower urinary tract symptoms (LUTS). The aim of the present review is to discuss to what extent TRP channels have adhered to their promise as new pharmacological targets in the lower urinary tract (LUT) and to outline the challenges that lie ahead. TRP vanilloid 1 (TRPV1) agonists have proven their efficacy in the treatment of neurogenic detrusor overactivity (DO), albeit at the expense of prolonged adverse effects as pelvic 'burning' pain, sensory urgency and haematuria. TRPV1 antagonists have been very successful in preclinical studies to treat pain and DO. However, clinical trials with the first generation TRPV1 antagonists were terminated early due to hyperthermia, a serious, on-target, side-effect. TRP vanilloid 4 (TRPV4), TRP ankyrin 1 (TRPA1) and TRP melastatin 8 (TRPM8) have important sensory functions in the LUT. Antagonists of these channels have shown their potential in pre-clinical studies of LUT dysfunction and are awaiting clinical validation.
Yves Deruyver,*‡¶ Thomas Voets,†¶ Dirk De Ridder,*‡¶ and Wouter Everaerts*<sup§¶
*Laboratory of Experimental Urology, Department of Development and Regeneration, †Laboratory for Ion Channel Research, Department of Molecular Cell Biology, KU Leuven, ‡University Hospitals Leuven, ¶TRP Research Platform Leuven (TRPLe), Leuven, Belgium, and §Royal Melbourne Hospital, Melbourne, Australia
April 2015: Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study
OBJECTIVES: To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients.
PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m2], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis.
RESULTS: Of the 965 patients, 383 (39.7%) were normal weight (BMI
CONCLUSION: In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer.
Alberto Abrate, Massimo Lazzeri, Giovanni Lughezzani, Nicolòmaria Buffi, Vittorio Bini*, Alexander Haese†, Alexandre de la Taille‡, Thomas McNicholas§, Joan Palou Redorta¶, Giulio M. Gadda, Giuliana Lista, Ella Kinzikeeva, Nicola Fossati, Alessandro Larcher, Paolo Dell'Oglio, Francesco Mistretta, Massimo Freschi** and Giorgio Guazzoni
Division of Oncology, Unit of Urology, URI, **Department of Pathology, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan, *Department of Internal Medicine, University of Perugia, Perugia, Italy, †Martini-Clinic Prostate Cancer Center, University Clinic Hamburg-Eppendorf, Hamburg, Germany, ‡Department of Urology, APHP Mondor Hospital, Créteil, France, §South Bedfordshire and Hertfordshire Urological Cancer Centre, Lister Hospital, Stevenage, UK, and ¶Urologic Oncology Section of the Department of Urology and Radiology Department, Fundaciò Puigvert, Barcelona, Spain