Potential Candidates for Focal Therapy in Prostate Cancer in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Large Multicenter Cohort Study.

BACKGROUND: Focal therapy (FT) with its favorable side-effect profile represents an option between active surveillance and traditional whole-gland treatment in localized prostate cancer (PCa). Consensus statements recommend eligibility criteria based on magnetic resonance imaging (MRI)-targeted and systematic combination biopsy. OBJECTIVE: To estimate the future potential of FT by analyzing the number of men eligible for FT among all men with biopsy-proven PCa and to judge the potential of different energy sources. DESIGN, SETTING, AND PARTICIPANTS: Consensus criteria on FT were analyzed. Patients with biopsy-proven PCa from six tertiary referral hospitals and one outpatient practice in Germany had received a software-based combination biopsy. Men with Prostate Imaging Reporting and Data System (PI-RADS) ≥3 lesions based on PI-RADS v2 were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were analyzed for potential treatment by FT and hemiablation. MRI lesions were mapped according to prostatic zones. RESULTS AND LIMITATIONS: In total, 2371 patients were analyzed. According to consensus criteria (biopsy-proven unifocal lesion of International Society of Urological Pathology [ISUP] grade group ≤2, prostate-specific antigen [PSA] ≤15ng/mL, and life expectancy >10yr), 303 patients (12.8%; ISUP 1: n=148 [6.2%]; ISUP 2: n=155 [6.5%]) were potential candidates for FT. A maximum PSA level of <10ng/mL would exclude further 60 (2.5%) of these men. The eligibility for hemiablation is slightly higher (16.2%). Unifocal lesions (n=288) were equally distributed within the prostate (anteriorly [31%], apically [29%], and dorsally [36%]). CONCLUSIONS: With adherence to consensus statements, only a minority of PCa patients present as potential candidates for FT. Distribution of tumor localization suggests the need for different energy modalities to warrant an optimal FT treatment. PATIENT SUMMARY: We analyzed how many men who receive a magnetic resonance imaging-targeted and systematic prostate biopsy are candidates for the experimental focal therapy of the prostate. When following expert recommendations, only a small number of men are potential candidates for this alternative treatment.

Diagnostic Performance of Multiparametric Magnetic Resonance Imaging and Fusion Targeted Biopsy to Detect Significant Prostate Cancer.

BACKGROUND/AIM: Multiparametric magnetic resonance imaging combined with ultrasound-fusion-targeted biopsy of the prostate intends to increase diagnostic precision, which has to be clarified. PATIENTS AND METHODS: We performed multiparametric magnetic resonance imaging followed by ultrasound-fusion-guided perineal biopsy in 99 male patients with elevated prostate-specific-antigen and previous negative standard biopsy-procedures. RESULTS: In 33/99 patients (33%) no malignancy could be confirmed by histopathology. Low-grade carcinomas (Gleason-Score 6+7a) were found in 42/66 (64%) and high-grade carcinomas (Gleason-Score ≥7b) in 24/66 (36%) men. A high-grade carcinoma corresponded to PI-RADS 4 or 5 (suspected malignancy) in 21/24 cases, which accounted for a sensitivity of 88% and negative-predictive-value of 85% (p=0.002). Differentiation between high-/low-grade carcinomas (Gleason-Score ≤7a vs. ≥7b) by means of PI-RADS related to a sensitivity of 88% and a negative-predictive-value of 70% (p=0.74). CONCLUSION: The results support the view that multiparametric magnetic resonance imaging/ultrasound-fusion-guided biopsy promotes considerably higher detection rates of clinically relevant prostate malignancies than do conventional diagnostic procedures. With regard to differentiation between high- and low-grade carcinomas, no significant difference was demonstrated.

[Diagnostic significance of multiparametric MRI combined with US-fusion guided biopsy of the prostate in patients with increased PSA levels and negative standard biopsy results to detect significant prostate cancer - Correlation with the Gleason score. Korrelation mit dem Gleason Score]. / Diagnostischer Stellenwert der multiparametrischen MRT mit gezielter Fusionsbiopsie der Prostata bei Patienten mit PSA-Anstieg und negativer Stanzbiopsie zur Detektion klinisch signifikanter Prostatakarzinome. Korrelation mit dem Gleason Score.

AIMS: To increase diagnostic precision and to reduce overtreatment of low-risk malignant disease, multiparametric MRI (mpMRI) combined with ultrasound (US) fusion guided biopsy of the prostate were performed. METHODS: In 99 male patients with increased PSA plasma levels and previous negative standard biopsy procedures, mpMRI was carried out followed by US fusion guided perineal biopsy. PI-RADS-Data (PS) of mpMRI and histopathological Gleason score (GS) were categorized and statistically compared. RESULTS: Lesions in 72/99 (73 %) of patients were determined to be suspect of malignancy, based on a PS 4 or 5. In 33/99 (33 %) of patients, malignancy could not be confirmed by histopathology. With regard to the remaining 66 patients with previous negative biopsy results, 42 (64 %) were diagnosed with a low-grade carcinoma (GS 6, 7a) and 24 (36 %) with a high-grade carcinoma (GS ≥ 7b). The proportion of corresponding results in mpMRI (PS 4-5) when a high-grade carcinoma had been detected, was 21/24 (88 %), which related to a sensitivity of 88 % and a negative predictive value (NPV) of 85 % (p = 0,002). In addition, 35 of 42 patients (83%), graded PS 4-5 in mpMRI, were diagnosed with low-grade carcinoma-positive (p < 0,001). Sensitivity to differentiation between low- and high-grade carcinomas (GS ≤ 7a vs. ≥ 7b) by means of PS was 88 % with a NPV of 70 % (p = 0,74). CONCLUSION: Our results suggest that mpMRI combined with US-fusion guided biopsy is able to detect considerably higher rates of clinically relevant prostate malignancies compared to conventional diagnostic procedures. However, no statistical significance could be shown regarding the differentiation between high- and low-grade carcinomas. It is hoped that the hybrid methods PSMA-PET/CT or PSMA-PET/MRI will lead to the next optimization step in the differentiation between high- and low-grade carcinomas which so far has been unsatisfactory.

[Thermal therapy of prostate cancer using magnetic nanoparticles]. / Termoterapia en cáncer de próstata mediante el uso de nanopartículas magnéticas.

A novel method of interstitial heating using magnetic nanoparticles and a direct injection technique has been evaluated in human cancers in recent clinical trials. In prostate cancer, this approach was investigated in two separate phase-I-studies, employing magnetic nanoparticle thermotherapy alone and in combination with permanent seed brachytherapy. The feasibility and good tolerability was shown in both trials, using the first prototype of a magnetic field applicator. As with any other heating technique, this novel approach requires specific tools for planning, quality control and thermal monitoring, based on appropriate imaging and modelling techniques. In these first clinical trials, a newly developed method for planning and non-invasive calculations of the 3-dimensional temperature distribution based on computed tomography could be validated. Limiting factors of this approach at present are patient discomfort at high magnetic field strengths and suboptimal intratumoral distribution of nanoparticles. Until these limitations will be overcome and thermal ablation can safely be applied as a monotherapy, this treatment modality is being evaluated in combination with irradiation in patients with localized prostate cancer.

Termoterapia en cáncer de próstata mediante el uso de nanopartículas magnéticas / Therman therapy of prostate cancer using magnetic nanoparticles

En recientes ensayos clínicos, se ha evaluado en tumores malignos humanos, un nuevo método de dispensación de calor en pequeños espacios (intersticios) utilizando nanopartículas magnéticas y una técnica de inyección directa. En el cáncer de próstata, este procedimiento se ha investigado en dos estudios fase I separados empleando en uno solamente termoterapia de nanopartículas magnéticas y en otro en combinación con braquiterapia (implantes permanentes). En ambos estudios se demostró viabilidad y buena tolerancia, usando el primer prototipo de un aplicador de campo magnético. Como con cualquier otra técnica por calor, este nuevo procedimiento requiere herramientas específicas para su planificación, control de calidad y monitorización térmica, basado en una imagen apropiada y en técnicas de planificación. En estos primeros estudios, se evalúa un nuevo método que permite una planificación y distribución tridimensional no invasiva de la temperatura basado en la tomografía computerizada (TC). En la actualidad, los factores limitantes de este procedimiento son el malestar del paciente a altas intensidades de campos magnéticos y la distribución intratumoral subóptima de las nanopartículas. Hasta que estas limitaciones sean superadas y la termoablación pueda ser aplicada con seguridad como monoterapia, esta modalidad de tratamiento está siendo evaluada en combinación con la irradiación en pacientes con cáncer de próstata localizado

A novel method of interstitial heating using magnetic nanoparticles and a direct injection technique has been evaluated in human cancers in recent clinical trials. In prostate cancer, this approach was investigated in two separate phase-I-studies, employing magnetic nanoparticle thermotherapy alone and in combination with permanent seed brachytherapy. The feasibility and good tolerability was shown in both trials, using the first prototype of a magnetic field applicator. As with any other heating technique, this novel approach requires specific tools for planning, quality control and thermal monitoring, based on appropriate imaging and modelling techniques. In these first clinical trials, a newly developed method for planning and non-invasive calculations of the 3-dimensional temperature distribution based on computed tomography could be validated. Limiting factors of this approach at present are patient discomfort at high magnetic field strengths and suboptimal intratumoral distribution of nanoparticles. Until these limitations will be overcome and thermal ablation can safely be applied as a monotherapy, this treatment modality is being evaluated in combination with irradiation in patients with localized prostate cancer

Flank hernia and bulging after open nephrectomy: mesh repair by flank or median approach? Report of a novel technique.

Flank incisions may be associated with flank hernias, which may be complicated with incarceration and strangulation. Furthermore, they may cause a significant limitation of the patient's quality of life. In the period 1997-2006 we performed 15 flank hernia repairs with a prosthetic mesh implantation. From 1997 to 2001 hernias were managed with a standardized mesh implantation through the initial flank incision (seven cases, flank group). Since 2001 we have adopted a novel operative approach in eight patients. Through a median laparotomy and following a transabdominally reduction of the hernia sac, a prosthetic polypropylene mesh [Prolene, Vypro or UltraPro, Ethicon Endo-Surgery (Europe) GmbH, Norderstedt, Germany] overlapping the midline was placed in a sublay technique (median group). The perioperative complication rate was comparable and they consisted mostly of postoperative seromas. A patient from the flank group developed a hernia recurrence two months after surgery. Thirteen patients participated in the annual follow-up for a total follow-up time of five years. In this period we observed only one additional case of hernia recurrence: a patient of the flank group presented with a 3 cm hernia recurrence at the proximal end of the previous operative incision. No recurrence was observed in the median group. As a result the novel technique for open repair of flank incisional hernias we present permits a remodelling of the abdominal wall and is associated with excellent postoperative results.

Multimodal fusion imaging ensemble for targeted sentinel lymph node management: initial results of an innovative promising approach for anatomically difficult lymphatic drainage in different tumour entities.

PURPOSE: There are situations where exact identification and localisation of sentinel lymph nodes (SLNs) are very difficult using lymphoscintigraphy, a hand-held gamma probe and vital dye, either a priori or a posteriori. We developed a new method using a simultaneous injection of two lymphotropic agents for exact topographical tomographic localisation and biopsy of draining SLNs. The purpose of this prospective pilot study was to investigate the feasibility and efficacy of this method ensemble. METHODS: Fourteen patients with different tumour entities were enrolled. A mixture of (99m)Tc-nanocolloid and a dissolved superparamagnetic iron oxide was injected interstitially. Dynamic, sequential static lymphoscintigraphy and SPECT served as pathfinders. MR imaging was performed 2 h after injection. SPECT, contrast MRI and, if necessary, CT scan data sets were fused and evaluated with special regard to the topographical location of SLNs. The day after injection, nine patients underwent SLN biopsy and, in the presence of SLN metastasis, an elective lymph node dissection. RESULTS: Twenty-five SLNs were localised in the 14 patients examined. A 100% fusion correlation was achieved in all patients. The anatomical sites of SLNs detected during surgery showed 100% agreement with those localised on the multimodal fusion images. SLNs could be excised in 11/14 patients, six of whom had nodal metastasis. CONCLUSION: Our novel approach of multimodal fusion imaging for targeted SLN management in primary tumours with lymphatic drainage to anatomically difficult regions enables SLN biopsy even in patients with lymphatic drainage to obscure regions. Currently, we are testing its validity in larger patient groups and other tumour entities.

Thermotherapy of prostate cancer using magnetic nanoparticles: feasibility, imaging, and three-dimensional temperature distribution.

OBJECTIVES: To investigate the feasibility of thermotherapy using biocompatible superparamagnetic nanoparticles in patients with locally recurrent prostate cancer and to evaluate an imaging-based approach for noninvasive calculations of the three-dimensional temperature distribution. METHODS: Ten patients with locally recurrent prostate cancer following primary therapy with curative intent were entered into a prospective phase 1 trial. The magnetic fluid was injected transperineally into the prostates according to a preplan. Patients received six thermal therapies of 60-min duration at weekly intervals using an alternating magnetic field applicator. A method of three-dimensional thermal analysis based on computed tomography (CT) of the prostates was developed and correlated with invasive and intraluminal temperature measurements. The sensitivity of nanoparticle detection by means of CT was investigated in phantoms. RESULTS: The median detection rate of iron oxide nanoparticles in tissue specimens using CT was 89.5% (range: 70-98%). Maximum temperatures up to 55 degrees C were achieved in the prostates. Median temperatures in 20%, 50%, and 90% of the prostates were 41.1 degrees C (range: 40.0-47.4 degrees C), 40.8 degrees C (range: 39.5-45.4 degrees C), and 40.1 degrees C (range: 38.8-43.4 degrees C), respectively. Median urethral and rectal temperatures were 40.5 degrees C (range: 38.4-43.6 degrees C) and 39.8 degrees C (range: 38.2-43.4 degrees C). The median thermal dose was 7.8 (range: 3.5-136.4) cumulative equivalent minutes at 43 degrees C in 90% of the prostates. CONCLUSION: The heating technique using magnetic nanoparticles was feasible. Hyperthermic to thermoablative temperatures were achieved in the prostates at 25% of the available magnetic field strength, indicating a significant potential for higher temperatures. A noninvasive thermometry method specific for this approach could be developed, which may be used for thermal dosimetry in future studies.

Transrectal broadband-Doppler sonography with intravenous contrast medium administration for prostate imaging and biopsy in men with an elevated PSA value and previous negative biopsies.

UNLABELLED: THE AIM of this study was to determine the prostate cancer detection rate of targeted biopsy using contrast-enhanced ultrasound (US) in patients with elevated prostate specific antigen (PSA) levels and previous negative biopsy. PATIENTS AND METHODS: A total of 114 patients initially underwent ultrasonography using transrectal ultrasound (TRUS) and power Doppler. All the patients had at least one previous biopsy series negative for prostate carcinoma. Ninety-five of the patients were examined with a new broadband Doppler technique, advanced dynamic flow (ADF), after i.v. injection of the echo enhancer (2.4 ml, SonoVue). The systematic biopsies were also obtained supplemented by removal of two targeted tissue cores in all the patients with a suspicious area in the inflow phase or late phase. RESULTS: Histology confirmed prostate cancer in 30 of the 95 patients. Sensitivity for the detection of prostate cancer by contrast-enhanced US was 100% and specificity was 48%. Suspicious areas were identified in 48 cases including 40 hypervascularized areas and 14 hypoechoic areas after 60 sec. Targeted biopsy identified 24 of the 30 carcinomas. Randomized octant biopsy identified only 8 of the 30 carcinomas. All 65 patients with negative histology were prostate cancer free at 12-month follow-up. The ADF US scans were degraded by fewer artifacts than the power Doppler images. CONCLUSION: Contrast-enhanced ADF Doppler allows reliable differentiation of prostate cancer and normal prostate tissue with a high sensitivity in patients with previous negative biopsy and fewer artifacts than power Doppler images, thus providing a good basis for targeted prostate biopsy instead of systematic biopsy.

Thermotherapy using magnetic nanoparticles combined with external radiation in an orthotopic rat model of prostate cancer.

BACKGROUND: We evaluated the effects of thermotherapy using magnetic nanoparticles, also referred to as magnetic fluid hyperthermia (MFH), combined with external radiation, in the Dunning model of prostate cancer. METHODS: Orthotopic tumors were induced in 96 male Copenhagen rats. Animals were randomly allocated to eight groups, including controls and groups for dose-finding studies of external radiation. Treatment groups received two serial thermotherapy treatments following a single intratumoral injection of magnetic fluid or thermotherapy followed by external radiation (10 Gy). On day 20, after tumor induction, tumor weights in the treatment and control groups were compared and iron measurements in selected organs were carried out. RESULTS: Mean maximal and minimal intratumoral temperatures obtained were 58.7 degrees C (centrally) and 42.7 degrees C (peripherally) during the first thermotherapy and 55.4 degrees C and 42.3 degrees C, respectively, during the second of two treatment sessions. Combined thermotherapy and radiation with 20 Gy was significantly more effective than radiation with 20 Gy alone and reduced tumor growth by 87.5-89.2% versus controls. Mean iron content in the prostates on day 20 was 87.5% of the injected dose of ferrites, whereas only 2.5% was found in the liver. CONCLUSIONS: An additive effect was demonstrated for the combined treatment at a radiation dose of 20 Gy, which was equally effective in inhibiting tumor growth as radiation alone with 60 Gy. Serial heat treatments were possible without repeated injection of magnetic fluid. The optimal treatment schedules of this combination regarding temperatures, radiation dose, and fractionation need to be defined in further experimental studies.

MRI of prostate cancer at 1.5 and 3.0 T: comparison of image quality in tumor detection and staging.

OBJECTIVE: This prospective study was performed to compare the image quality, tumor delineation, and depiction of staging criteria on MRI of prostate cancer at 1.5 and 3.0 T. SUBJECTS AND METHODS: Twenty-four patients with prostate cancer underwent MRI at 1.5 T using the combined endorectal-body phased-array coil and at 3.0 T using the torso phased-array coil, among them 22 before undergoing radical prostatectomy. The prostate was imaged with T2-weighted sequences in axial and coronal orientations at both field strengths and, in addition, with an axial T1-weighted sequence at 1.5 T. Preoperative analysis of all MR images taken together was compared with the histologic findings to determine the accuracy of MRI for the local staging of prostate cancer. In a retroanalysis, the image quality, tumor delineation, and conspicuity of staging criteria were determined separately for both field strengths and compared. Statistical analysis was performed using Wilcoxon's and the McNemar tests. RESULTS: In the preoperative analysis, MRI (at both 1.5 and 3.0 T) had an accuracy of 73% for the local staging of prostate cancer. The retroanalysis yielded significantly better results for 1.5-T MRI with the endorectal-body phased-array coil in terms of image quality (p < 0.001) and tumor delineation (p = 0.012) than for 3.0-T MRI with the torso phased-array coil. Analysis of the individual staging criteria for extracapsular disease did not reveal a superiority of either of the two field strengths in the depiction of any of the criteria. CONCLUSION: Intraindividual comparison shows that image quality and delineation of prostate cancer at 1.5 T with the use of an endorectal coil in a pelvic phased-array is superior to the higher field strength of 3.0 T with a torso phased-array coil alone. As long as no endorectal coil is available for 3-T imaging, imaging at 1.5 T using the combined endorectal-body phased-array coil will continue to be the gold standard for prostate imaging.

Matrix metalloproteinase inhibitor Ro 28-2653 in combination with estramustine: tumor-reducing effects on hormone-sensitive prostate cancer in rats.

Therapeutic efficacy of the novel matrix metalloproteinase (MMP) inhibitor, Ro 28-2653 (5-biphenyl-4-yl-5-[4-(-nitro-phenyl)-piperazin-1-yl]-pyrimidine-2,4,6-trione), has been shown in various models of different tumor entities. The tumor growth-reducing effect has been demonstrated in the orthotopic rat prostate Dunning model (subline MatLyLu). Based on these results we investigated Ro 28-2653 in combination with estramustine on the G subline of the Dunning tumor. This subline is characterized by a low metastatic ability and androgen sensitivity. Efficacy was determined by recording tumor growth in vivo by magnetic resonance imaging (MRI). Tumor cells were injected into the prostates of 81 Copenhagen rats. MRI was performed at day 100 and at day 126 after tumor cell injection. The duration of therapy was 17 days with daily oral application of Ro 28-2653 (100 mg/kg) and four i.p. injections of estramustine (7.5 mg/kg). Histological evaluations were conducted to provide further information about the effects on tumor morphology. Orthotopic tumor induction was successful in 100% of the animals. Tumor volume calculations with MRI showed a significant difference between the control groups, the animals treated with Ro 28-2653, and the animals treated with the combination of Ro 28-2653 and estramustine. The new MMP inhibitor Ro 28-2653 reduces tumor growth and provides a compatible therapeutic alternative for patients with prostate cancer.

Magnetic fluid hyperthermia (MFH)reduces prostate cancer growth in the orthotopic Dunning R3327 rat model.

BACKGROUND: Magnetic fluid hyperthermia (MFH) is a new technique for interstitial hyperthermia or thermoablation based on AC magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. Preliminary studies in the Dunning tumor model of prostate cancer have demonstrated the feasibility of MFH in vivo. To confirm these results and evaluate the potential of MFH as a minimally invasive treatment of prostate cancer we carried out a systematic analysis of the effects of MFH in the orthotopic Dunning R3327 tumor model of the rat. METHODS: Orthotopic tumors were induced by implantation of MatLyLu-cells into the prostates of 48 male Copenhagen rats. Animals were randomly allocated to 4 groups of 12 rats each, including controls. Treatment animals received two MFH treatments following a single intratumoral injection of a magnetic fluid. Treatments were carried out on days 10 and 12 after tumor induction using an AC magnetic field applicator system operating at a frequency of 100 kHz and a variable field strength (0--18 kA/m). On day 20, animals were sacrificed and tumor weights in the treatment and control groups were compared. In addition, tumor growth curves were generated and histological examinations and iron measurements in selected organs were carried out. RESULTS: Maximum intratumoral temperatures of over 70 degrees C could be obtained with MFH at an AC magnetic field strength of 18 kA/m. At a constant field strength of 12.6 kA/m, mean maximal and minimal intratumoral temperatures recorded were 54.8 degrees C (centrally) and 41.2 degrees C (peripherally). MFH led to an inhibition of tumor growth of 44%-51% over controls. Mean iron content in the prostates of treated and untreated (injection of magnetic fluids but no AC magnetic field exposure) animals was 82.5%, whereas only 5.3% of the injected dose was found in the liver, 1.0% in the lung, and 0.5% in the spleen. CONCLUSIONS: MFH led to a significant growth inhibition in this orthotopic model of the aggressive MatLyLu tumor variant. Intratumoral deposition of magnetic fluids was found to be stable, allowing for serial MFH treatments without repeated injection. The optimal treatment schedules and temperatures for MFH need to be defined in further studies.

Thermoradiotherapy using interstitial self-regulating thermoseeds: an intermediate analysis of a phase II trial.

OBJECTIVE: Thermoradiotherapy in the treatment of prostate cancer is based on a variety of experimental and clinical phase I data which have proven the synergistic effects of this combination. We report on a phase II trial in a special hyperthermia research group (SFB 273) of the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) to determine feasibility, acute toxicity and efficacy of this combination for prostate cancer. METHODS: 57 patients with localized prostate cancer were treated with interstitial hyperthermia using cobalt-palladium thermoseeds and conformal radiation between July 1997 and December 2000. Thermoseeds were placed into the prostate homogeneously. Hyperthermia was created using a magnetic field and was delivered in six sessions once weekly for one hour. 3D-conformal radiotherapy of 68.4Gy was given simultaneously in daily fractions of 1.8Gy. RESULTS: Intraprostatic temperatures were between 42 and 46 degrees C. No major side effects were observed during hyperthermia. Median follow-up was 36 months (range 3-72 months). Median PSA value decreased from 11.6ng/ml to 2.4ng/ml 3 months after treatment, to 1.3ng/ml 12 months after treatment and to 0.55ng/ml 2 years after therapy. CONCLUSION: Interstitial hyperthermia is feasible, well tolerated and led to a steep decrease of PSA values. Combining effective interstitial hyperthermia with conformal radiotherapy may be an exciting innovative treatment option for prostate cancer.

A multicenter clinical trial on the use of complexed prostate specific antigen in low prostate specific antigen concentrations.

PURPOSE: The determination of complexed prostate specific antigen (cPSA) has been suggested to be promising for prostate cancer (PCa) diagnosis. In a multicenter trial we evaluate the diagnostic use of PSA forms in the low total PSA (tPSA) range. MATERIALS AND METHODS: A total of 283 white men with and 417 without PCa and tPSA concentrations between 0 and 6 ng/ml were retrospectively analyzed. All 700 untreated subjects underwent a multisector needle biopsy of the prostate. The Elecsys analyser 1010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and free PSA. Determination of cPSA and tPSA was performed using immunoassays of the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, New York). RESULTS: Receiver operating characteristics analyses for discrimination between cases with and without PCa were performed. The areas under the curves (AUC) for cPSA, tPSA and free-to-total PSA (f/tPSA) showed no significant differences in the tPSA ranges of 0 to 6 (700 cases), 0 to 4 (510) and 0.5 to 2.5 ng/ml (253). Within the tPSA range of 2.5 to 4 ng/ml (230 cases) the AUC for cPSA (0.61) was significantly larger than that for tPSA (Roche 0.51, Bayer 0.54) but did not differ from the AUC of f/tPSA (Roche). On the basis of the cutoffs for 95% specificity or sensitivity, no significant increase in corresponding sensitivity or specificity was found between tPSA with cPSA. CONCLUSIONS: In the tPSA range of less than 4 ng/ml no improvement in diagnostic accuracy was shown between cPSA with tPSA or the ratio of f/tPSA. The search for a useful marker in the low PSA range must continue.

Effects of 13-cis-retinoic acid on chemoimmunotherapy of metastatic renal cell carcinoma--results of a retrospective analysis.

Chemoimmunotherapy (CIT) with interleukin-2, interferon-alpha2a, and 5-fluorouracil is an accepted treatment option of metastatic renal cell carcinoma (mRCC). Because of the enhancement of the antiproliferative effects of interferon-alpha2a, 13-cis-retinoic acid (13-CRA) might be of potential usefulness for immunotherapy. We have investigated the effect of 13-CRA in patients treated with chemoimmunotherapy. Seventy-two patients with mRCC and a Karnofsky performance index > or = 80% were retrospectively analyzed. Thirty-six patients received chemoimmunotherapy and 36 other patients were treated similarly but with addition of daily 60 mg 13-CRA. Response was assessed according to the UICC criteria. Survival was calculated by Kaplan Meier estimation and compared with the log-rank test. In the CIT group objective remissions occurred in 34.3% (95% CI 19.1-52.2) and stabilizations in 42.9% (median follow-up 16 months). In the CIT plus 13-CRA group, objective remissions were seen in 26.4% (95% CI 12.9-44.4) and stabilizations in 50% (median follow-up 17 months). One- and three-year survival rates were 76% and 32% in the CIT group and 82% and 37% in the CIT plus 13-CRA group. The combination of CIT and 13-CRA did not significantly differ in objective remissions and estimated survival compared with CIT. Our retrospective data suggest that 13-CRA does not enhance the therapeutic efficacy of CIT in mRCC patients with a good performance status.