Complexed prostate-specific antigen, complexed prostate-specific antigen density of total and transition zone, complexed/total prostate-specific antigen ratio, free-to-total prostate-specific antigen ratio, density of total and transition zone prostate-specific antigen: Results of the prospective multicenter European trial

This prospective, multicenter European Prostate Cancer Detection study evaluated the value and performance of the molecular forms of prostate-specific antigen (PSA) and their derivatives in combination with prostate gland and transition zone volumes in early detection of prostate cancer in patients with PSA levels between 4 and 10 ng/mL. Of 750 men enrolled at 7 different European urology centers into the study between November 2001 and March 2002, 340 (45.3%) had a total PSA (tPSA) between 4 and 10 ng/mL (age range, 46 to 87 years). In all patients, the ratio of complexed PSA (cPSA) to tPSA (c/tPSA), cPSA density (cPSAD), cPSAD of the transition zone, PSA, free PSA (fPSA), ratio of fPSA to tPSA (f/tPSA), tPSA density (PSAD), and PSAD of the transition zone were measured and collected 5 to 10 minutes before the sextant biopsy with 2 additional transition zone cores. Measurements of tPSA and fPSA were done with the AxSYM test, whereas cPSA was measured with the ACS 180 cPSA assay. All patients had a transrectal ultrasound-guided sextant prostate biopsy, and 2 additional transition zone biopsies and total and transition zone volumes were measured at the time of biopsy. Histopathologic findings revealed benign histology in 237 patients and prostate cancer in 103 patients (69.7% and 30.3%, respectively). Statistically significant differences included larger total volumes, larger transition zone volumes, and f/tPSA in patients with benign disease (P = 0.0009, P <0.0001, P <0.0001, respectively). At 90% and 95% sensitivity, specificity of cPSA was significantly greater than that for PSA (P <0.0001). At sensitivity levels of 90% and 95%, the specificity of the cPSA assay using cutoff values of 3.06 and 2.52 ng/mL was 20.3% and 9.1%, respectively. A cPSA cutoff value of 6.95 ng/mL and 7.57 ng/mL afforded 90% and 95% specificity for detecting prostate cancer. The area under the curve (AUC) in the receiver operating characteristics curve of cPSA was statistically significantly higher compared with tPSA (60.8 vs 56.9, P = 0.032). AUC for volume-related parameters PSAD, cPSAD, PSAD of the transition zone, and cPSAD of the transition zone were 62.8%, 63.1%, 63.0%, and 63.6%, respectively. cPSA performs better than tPSA in the differentiation between benign disease and prostate cancer and provides similar information to the f/tPSA ratio. In addition, cPSA and cPSA volume-related parameters (cPSAD, cPSAD of the transition zone) further improved the specificity of PSA in early detection of prostate cancer. © 2002, Elsevier Science Inc.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Therapie des kastrationsrefraktären Prostatakarzinoms

Zusammenfassung Innerhalb der letzten zwei Jahre hat die Therapie des kastrationsrefraktären Prostatakarzinoms (CRPC) große Fortschritte gemacht. Sowohl die COU-AA-301 Phase-III-Studie als auch die TROPIC Studie zeigten einen Überlebensvorteil für Patienten nach Docetaxel-Versagen, die mit Abirateron beziehungsweise Cabazitaxel behandelt wurden. In einem Umfeld von wachsendem Interesse an chemotherapeutischen Optionen und neuen Medikamenten war es unser Ziel, als multidisziplinäres Team die verfügbare Datenlage zu analysieren und einen Standard für die medizinische Behandlung des Prostatakarzinoms außerhalb klinischer Studien zu definieren. Vor diesem Hintergrund evaluieren wir die momentanen Behandlungsempfehlungen sorgfältig und auf Basis der verfügbaren Anhaltspunkte, beleuchten mögliche zukünftige Behandlungsoptionen und diskutieren wichtige klinische Themen wie die Behandlung bis zur Progression versus den Vorteilen von Chemoholidays und die Definition bestimmter Patientensubgruppen. Zusätzlich legen wir besonderes Augenmerk auf neue molekulare Wirkstoffklassen, deren Verfügbarkeit in naher Zukunft erwartet wird, wie z. B. MDV3100 und Sipuleucel T. Die Rolle und Bedeutung der Palliation mittels Strahlentherapie und der proaktiven medikamentösen analgetischen Therapie wird ebenso diskutiert wie neue Therapieoptionen der mit Knochenmetastasen assoziierten Beschwerden. Die Vielzahl an Behandlungsoptionen für Patienten mit fortgeschrittenem Prostatakarzinom verlangt eindeutig eine enge Zusammenarbeit zwischen Urologen, Onkologen und Strahlentherapeuten. Summary Within the last two years the therapy of castration resistant prostate cancer (CRPC) has made major advances. Both the COU-AA-301 phase III trial and the TROPIC trial showed a survival benefit for patients after docetaxel failure treated with abiraterone or cabazitaxel, respectively. With rising interest for chemotherapeutic options and novel drugs, our goal was to review within the context of a multidisciplinary team the available evidence and explore the standards for medical treatment of prostate cancer outside of clinical trials. From this background, we are carefully evaluating the current treatment recommendations, based on the available evidence, and highlight potential future treatment options but also discuss important clinical topics like treatment until progression versus the advantage of chemo holidays and definition of particular patient subgroups. Additionally, we focus on novel molecular entities, which will most likely be available in the near future, such as MDV3100 and Sipuleucel T. The role and importance of palliation with radiotherapy and proactive medical management of pain is also discussed, as well as new options for bone directed therapy. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists