Robin Epplen

Sextant-Specific Analysis of Detection and Tumor Volume by HistoScanning™.

Introduction: Published results of HistoScanning™ (HS) for prostate cancer (PCa) diagnostics are inconsistent and their value remains unclear. We prospectively analyzed the detection rate and tumor volume concordance in PCa patients. Material and Methods: Two hundred and eighty-two patients with biopsy-proven PCa scheduled for radical prostatectomy (RP) were included. All patients underwent ultrasonographical examination by HS prior to surgery. HS was evaluated compared to RP specimen as to (1) the prediction of overall tumor volume and (2) accuracy of HS in detection of PCa lesions larger than 0.2/0.5 ml, separated for each sextant. For each sextant, receiver operating characteristic (ROC)-analysis and area under the curve were determined. Sensitivity and specificity were calculated and visualized in ROC-curves. Results: HS tends to underestimate volume of cancerous lesions, particularly larger lesions >8 ml. Using a 0.2 ml detection threshold, specificity and sensitivity of HS were between 29-68% and 46-78%. For a 0.5 ml detection threshold, sextant-specific specificity increased to 59-92% and sensitivity decreased to 16-54%. Stratification according to pre-operational PSA values did not improve performance characteristics of HS. Conclusions: Our results do not support a significant contribution of HS to PCa diagnostics.

Differential effects of ibandronate, docetaxel and farnesol treatment alone and in combination on the growth of prostate cancer cell lines

Abstract Ibandronate, one of the most potent bisphosphonates, has been shown to inhibit growth of various cancer cell lines. In contrast, little is known about the effects of ibandronate on prostate cancer cells. Therefore the aim of our study was to characterize the effects of ibandronate alone and in combination with docetaxel on the growth of prostate cancer cell lines and to identify the underlying signalling pathways. Material and methods. The prostate cancer cell lines LNCaP and PC-3 were treated with increasing concentrations of ibandronate and docetaxel alone and in combination. Viable cell number was measured after five days using a hemocytometer and the MTT-method. The effects of ibandronate were tentatively antagonized by addition of farnesyl-pyrophosphate (FPP) or farnesol (FOH). Results. Ibandronate inhibits growth of both prostate cancer cell lines in a dose dependent manner. In combination with docetaxel, synergistic effects are found as evidenced by a combination index (CI) of <1. Addition of FOH and FPP completely antagonized the growth inhibitory effects of ibandronate on both cell lines. Surprisingly, in combination with ibandronate and docetaxel, FOH further increased growth inhibition instead of antagonizing the growth inhibitory effects of ibandronate. Furthermore, FOH alone appeared to be a potent inhibitor of tumor cell growth. Discussion. Ibandronate effectively inhibits growth of prostate cancer cell lines via inhibition of the farnesyl-IPP-synthase and exhibits synergistic effects with docetaxel. In addition, FOH is a potent inhibitor of prostate cancer cell lines and may display an interesting treatment option for patients with CRPC.

Evaluation of (18F) FDG-PET-CT for preoperative lymph-node staging of bladder cancer.

275 Background: Radical cystectomy with extended pelvic lymphadenectomy (EPLA) is the treatment of choice for muscle-invasive bladder cancer. For preoperative staging computed tomography and magnetic resonance imaging of the abdomen and the small pelvis are most commonly used in daily routine.Since the aforementioned methods, have a low sensitivity to detect local lymph node metastasis (LNM) we have prospectively evaluated the role of FDG - PET/CT for locoregional staging. METHODS In 27 patients (n = 27) with known invasive urothelial carcinoma or squamous cell carcinoma of the bladder a staging FDG - PET - CT was performed 1-2 days prior to radical cystectomy with EPLA. Subsequently, the results of the histopathological work-up of lymph node specimens and their anatomical localisations were correlated to the FDG-PET/CT findings. Total of 452 lymph nodes were removed, on average ≈ 16.7 per patient. RESULTS In 3/27 (11.1%) patients LNM were detected in histopathology. 2 patients showed one positive lymph node, 1 patient had two LNM. In two of these patients, the FDG-PET/CT showed an increased enrichment of FDG in projection to the corresponding histologically positive LN. One false negative and one false positive result of FDG-PET/CT were found. Calculated based on the patient population, the following statistics were calculated: Sensitivity (SENS) 66%, specificity (SPEC) 95.8%, positive predictive value (PPV) 66%, negative predictive value (NPV) 95.8%. Related to the absolute number of LN (n = 452), the following numbers were calculated: SENS 75% SPEC 98.7, PPV 37.5%, NPV 99.7%. CONCLUSIONS To date, few studies have been conducted with regard to FDG-PET/CT and its role in locoregional staging. The reported specificity and NPV was between 86% and 100%, sensitivity and PPV were between 50% and 100%. Our results demonstrate specificity and NPV values of larger than 90% and make FDG-PET/CT a valuable staging tool to potentially identify patients with negative nodes in whom EPLA could be safely ommitted. Curently, routine use of PET CT scans can not be recommended and it is currently tested in a prospective multicenter study including a larger patient cohort.

Radical salvage prostatectomy for locally recurrent prostate cancer after radiation therapy.

47 Background: Radical salvage prostatectomy (SRP) is one local treatment option with curative intent in patients failing radiation therapy (RT) for localized prostate cancer (PCA). We compared the surgical, histological and functional outcome of a large cohort of patients who underwent SRP for locally recurrent PCA following LDR - brachytherapy (BRT). METHODS 66 consecutive patients with locally recurrent PCA after BRT underwent retropubic SRP and pelvic lymphadenectomy. Preoperative PSA, PSA doubling time, PSA prior to initial RT, biopsy Gleason score, number of positive biopsies, cT stage, neoadjuvant androgen deprivation were correlated with pathohistological stage, complications and functional outcome by uni- and multivariate analysis. RESULTS Mean preop. PSA was 5.6 (2-13.5) ng/ml; mean preoperative biopsy Gleason score was y5.6 (4-9). 1 patient (1.5%) experienced a rectal lesion, mean blood loss was 430 (200-900) ml, none of the patients received blood transfusions. Pathohistology demonstrated organ confined prostate cancer pT2a-2c in 38 (57.5%) patients, stage pT3a and stage pT3b was identified in 14 (21.1%) patients and in 14 (21.1%) patients, respectively. Positive surgical margins were diagnosed in 9 (13.6%) patients and 12 (15.1%) patients harboured lymph node metastases. Functional outcome was good with a continence rate of 82%; the mean time until recovery of continence was 8.4 (6-14) months. After a mean follow-up of 22.5 (1-72) months, 28% of the patients experienced a PSA relapse defined as any PSA increase > 0.2 ng/ml validated by 2 consecutive measures. CONCLUSIONS SRP can be performed safely and with a low morbidity in biopsy proven locally recurrent PCA following BRT. However, our data demonstrate an unfavourable histology with locally advanced disease in about 40% of the patients who all were diagnosed with low risk prostate cancer. These data question the quality of the selection process for patients being counselled for BRT and the data raise the possibility of both intrinsic radioresistance of prostate cancer or poorly performed BRT.

Frequency and prognostic significance of the PSA flare-up phenomenon in men with castration-resistant prostate cancer (CRPC) who undergo docetaxel-based chemotherapy.

92 Background: Chemotherapy with docetaxel and prednisone represents the guideline-recommended first-line therapy in men with metastatic CRPC. Until now there is a lack of information with regard to the oncological efficacy, survival and treatment-associated toxicity in patients who are treated in the community beside clinical trials. METHODS 487 patients were prospectively recruited according to a standardized questionnaire within a 1-year time interval. Patients were treated in 144 institutions who contributed between 2 and 48 patients. The mean age was 73.4 (41 - 85) years, the mean PSA level was 135.9 (2.1 - 1.895) ng/ml. 445 (91.5%) patients had bone metastases and/or lymph node metastases. Cardiovascular, pulmonary, neurological or endocrinological comorbidities were present in 157 (27.5%) patients. RESULTS The mean follow-up was 24 (15-36) months. A mean of 6.6 (1-21) cycles docetaxel were delivered. 101 (20.7%) patients received 1-3 cycles, 222 (45.6%) patients received 4-6 cycles and 167 (34.3%) patients underwent 7-10 cycles. 29 (5.9%) and 295 (61.4%) patients achieved a complete or partial remission, respectively; 95 (19.5%) and 19 (3.9%) patients demonstrated stable disease or progression, respectively. An immediate, delayed (flare-up) or no PSA response was achieved in 40.9%, 29.9% and. 21.8%, respectively. During follow-up 192 (40.6%) patients developed progressive disease. 49 (10.4%) patients died, 37 (7.8%) died due to cancer progression. The mean and median progression-free survival was 256.6 ± 14.8 and 216 days, respectively. The mean and median overall survival was 394 ± 10.7 and 476 days, respectively. Significant Grad 3/4 toxicities were identified in 46 (9.4%) patients with predominantly hematotoxicity and gastrointestinal toxicity. CONCLUSIONS We were able to reproduce the therapeutic response rate of clinical studies with a selected pool of patients. We verified the efficacy of docetaxel in general in patients with CRPC. A flare-up phenomenon within the first three cycles was observed in 30% of patients, which suggest to continue therapy for at least that period of time.

Is histoscanning a valid tool to detect prostate cancer in repeat biopsy

57 Background: Histoscanning is a novel ultrasound-based software programme, which uses back-scattered ultrasound, to detect and visualize prostate carcinoma. It is not clear to date which additive information histoscanning will deliver terms of additive information to ultrasound guided transrectal biopsy as research is scarce.Therefore we aimed to analyze our data on repeat biopsy with histoscanning prior to intervention. METHODS From Sept. 2009 till present, 61 patients, mean age 62 yrs, that were scheduled for repeat biopsy received Histoscanning prior to intervention. Acquired data were retrospectively processed with Histoscanning software version 2.2 and prostate was divided into a 6 grid pattern. Lesions ≥0,5ml were considered positive. Biopsies were taken according to Vienna normogram and processed by an experienced uropathologist. RESULTS Mean number of biopsies prior to repeat was 2. Mean PSA at repeat biopsy was 7,135 ng/ml, mean prostate volume accounted for 45.5 ml. A total of 15/61 men were diagnosed with cancer (24,59%), Gleason Score (Gl.) of 6 n=10, n=2 Gl. 3+4=7, n=2 Gl. 4+4; n=2 Gl. 4+5=9 respectively. A total of 43/834=5.15% positive cores were obtained, averaging 0.7 per person. Mean Volume of Histoscanning lesions per scan: 1,48 ml; no statistical significance can be detected regarding the volume per sextant and a positive core. False positive rate was 90/366=24,6%; false negative rate was 19/366=5,2%. Overall sensitivity was 29,69%, specifity accounted for 73.3%. PPV was calculated at 8.16% and NPV at 92,88%. PSA had no influence on detection rate. CONCLUSIONS In this highly seleted patient cohort Histoscanning had no beneficial nor additive information on detecting prostate cancer. Further research should has to be done regarding Histoscanning lesions with different histopathological features such as prostatitis and fibrosis.

Palliative transurethral resection in men with castration-resistant prostate cancer (CRPC): Minimally invasive procedure with minimal morbidity?

233 Background: About 20 to 30% of men with CRPC with a prostate in situ will develop subvesical obstruction due to locally progressing prostate cancer with time. Treatment options include palliative TURP, urinary diversion by transurethral or suprapubic catheters. There are only few reports critically evaluating the outcome of palliative TURP and the development of associated symptoms of locally progressing CRPC. METHODS We retrospectively reviewed all patients who underwent palliative TURP for locally advanced CRPC with regard to the functional and oncological outcome. In addition, we analysed the frequency of complications associated with locally advanced (LA) CRPC. Patient with incidental prostate cancer were excluded from the analysis. RESULTS Between 2004-2010 a total of 83 patients were identified. The mean age of the patients was 76 (60-91) years. Mean PSA at time of TURP was 78 (1-253) ng/ml. Initial therapy included androgen deprivation monotherapy in 67.8%, radiation therapy in 28.6% and active surveillance in 3.4%.The mean size of the prostate was 40 (15-130) ml, the mean resected prostate weight was 18.6 (2-56) g. The mean Gleason score was 8.3 (6-10). The indication for palliative TURP was subvesical obstruction with a postvoid residual urine > 100ml in 68.8 %, recurrent gross hematuria in 13.2% and acute urinary retention in 18.1%. 19 (2.9%) pts demonstrated uni- or bilateral upper urinary tract obstruction necessitating drainage by endoluminal stenting or percutaneous nephrostomy. The mean catheterization time was 3.4 (2-6) days; postoperative complications developed in 15 (18.1%) pts and included: urinary retention in 2 pts, intravesical blood clots in 3 pts, permanent suprapubic catheter in 3 pts, stress urinary incontinence in 2 pts and re-do TURP in 3 pts. Perioperative mortality was 0% and after a mean follow-up of 3.6 years, 27 (32.5%) pts had died due to prostate cancer. CONCLUSIONS Palliative TURP in men with LA-CRPC is fairly safe, but side effects are higher compared to conventional TURP. Due to a high frequency of involvement, the upper urinary tract has to be screened prior to palliative TURP.

Functional and oncologic outcomes of nephron-sparing surgery (NSS) for patients with renal cell carcinoma (RCC) greater than 4 cm in diameter.

347 Background: Organ preserving surgery represents the guideline recommended surgical treatment of choice for patients with small renal tumors ≤ 4cm in diameter. There are only few data in the literature with regard to the oncological and functional outcome of elective NSS in RCC larger than 4cm. METHODS We retrospectively reviewed the charts of all patients who underwent elective NSS for RCC at our institution during 2004-2009. We identified 288 patients of whom 196 (68.1%) patients and 92(31.9%) patients underwent NSS for a tumor < 4cm (group 1) and a tumour ≥ 4cm (group 2), respectively. We analyzed tumor size, TNM-classification, OR time, surgical margins, complications, mortality, recurrences and metastases in both groups. RESULTS We identified significant differences between group 1 and 2 for the following variables: mean tumor size (2.9 vs. 8.6cm, p = 0.03), necessity for warm ischemia (15.1% vs. 51%, p = 0.001), mean ischemia time (3.5 vs. 10.2 min, p = 0.002), need for endoluminal stenting due to involvement of the renal pelvis (0.5% vs. 24.2%, p = 0.001). Significantly less pT2 (12.7% vs. 29.7%, p = 0.03) and pT3 tumors (8.7% vs. 12%, p = 0.05) were identified in group 1 when compared to group 2. There were no significant differences with regard to mean OR time (61 vs. 74 min), positive surgical margins (1/192 vs. 1/92), hospital stay, and perioperative complications. There were no significant differences with regard to stage specific overall survival, cancer-specific survival and progression-free survival. There was no significant survival difference between NSS and radical nephrectomy. CONCLUSIONS NSS can be safely performed in RCC > 4 cm without increasing the frequency of treatment-associated complications or decreasing cancer-specific survival. NSS should represent the treatment of choice in all patients with RCC of 4-7cm in diameter if technically feasible. No significant financial relationships to disclose.