68Ga-PSMA PET/CT based primary staging and histological correlation after extended pelvic lymph node dissection at radical prostatectomy.

INTRODUCTION: Prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET/CT) represents the upcoming standard for the staging of prostate cancer (PCa). However, there is still an unmet need for the validation of PSMA PET/CT at primary staging and consecutive histological correlation. Consequently, we decided to analyze the prediction parameter of PSMA PET/CT at primary staging. METHODS: We relied on 90 ≥ intermediate-risk PCa patients treated with radical prostatectomy (RP) and extended pelvic lymph node dissection. All patients were administered to 68Ga-PSMA PET/CT prior to surgery. 68Ga-PSMA PET/CT data were retrospectively reevaluated by a single radiologist and consequently compared to histological results from RP. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of lymph node metastases were analyzed per-patient (n = 90), per-pelvic side (n = 180), and per-anatomic-region (external iliac artery and vein left/right vs. obturator fossa left/right vs. internal iliac artery left/right) (n = 458), respectively. RESULTS: Sensitivity, specificity, PPV, and NPV per-patient were: 43.8, 96.0, 70.0, and 88.8%, respectively. Sensitivity, specificity, PPV, and NPV per-pelvic-side were: 42.9, 95.6, 56.3, and 92.7%, respectively. Sensitivity, specificity, PPV, and NPV per-anatomic-region were: 47.6, 98.9, 66.7, and 97.5%, respectively. CONCLUSIONS: Negative 68Ga-PSMA PET/CT results were highly reliable in our study. Positive 68Ga-PSMA PET/CT results, however, revealed less reliable results. Larger and ideally prospective trials are justified to clarify the potential role of PSMA PET/CT based primary staging.

Construction of a penoid after penectomy using a transpositioned testicle.

Total penectomy results in a disfiguring anatomic situation which may have a devastating effect on the patient's psychologic health. Here we report our experience with construction of a penoid by covering a transpositioned testicle with remaining penile skin after radical penectomy in 2 patients with malignant underlying disease.

Muscle-derived cells for treatment of iatrogenic sphincter damage and urinary incontinence in men.

INTRODUCTION: Aim of this study was to assess the safety and efficacy of injection of autologous muscle-derived cells into the urinary sphincter for treatment of postprostatectomy urinary incontinence in men and to characterize the injected cells prior to transplantation. METHODS: 222 male patients with stress urinary incontinence and sphincter damage after uroloical procedures were treated with transurethral injection of autologous muscle-derived cells. The transplanted cells were investigated after cultivation and prior to application by immunocytochemistry using different markers of myogenic differentiation. Feasibility and functionality assessment was achieved with a follow-up of at least 12 months. RESULTS: Follow-up was at least 12 months. Of the 222 treated patients, 120 responded to therapy of whom 26 patients (12%) were continent, and 94 patients (42%) showed improvement. In 102 (46%) patients, the therapy was ineffective. Clinical improvement was observed on average 4.7 months after transplantation and continued in all improved patients. The cells injected into the sphincter were at least ~50% of myogenic origin and representative for early stages of muscle cell differentiation. CONCLUSIONS: Transurethral injection of muscle-derived cells into the damaged urethral sphincter of male patients is a safe procedure. Transplanted cells represent different phases of myogenic differentiation.

A phase II trial of temsirolimus in second-line metastatic urothelial cancer.

This phase II trial assessed temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR), as second-line therapy in patients with metastatic transitional carcinoma of the urothelium (TCCU) after failure of platinum containing therapy. From June/2009 to June/2011, we enrolled 15 patients in this trial. Primary endpoint was overall survival, as secondary endpoints we defined time to disease progression, safety and QoL along treatment. Patients with progressive TCCU after prior platinum-based chemotherapy received weekly 25 mg of temsirolimus for 8 weeks. Evaluation for response was accomplished every 8 weeks according to the RECIST criteria, QoL assessment was done every 4 weeks using the QLQ-C30 questionnaire, adverse events (AEs) were recorded and graded using NCI-CTC criteria. Fifteen patients were enrolled in this study, of whom 14 (93%) were available for activity, safety and QoL assessment. We treated 10 (71%) male and 4 female (29%) patients. Median age was 64,7 years (45-76). Patients received on average 13 (3-15) infusions of temsirolimus. As per protocol, no sufficient benefit on overall survival was observed, we early stopped the study after 14 patients. Median time to progression was 2.5 months (77 days), median overall survival was 3.5 months (107 days). Four patients with stable disease were observed. QoL assessment along treatment revealed a reduction of EORTC-QLQ-C30, Global Health Status subscale, from initial 7.86 to 5.00. Temsirolimus was well tolerated. As Grade 3-4 adverse events, we observed fatigue (n=2), leukopenia (n=2) and thrombopenia (n=2). All other adverse events were graded 1-2 in nature. Temsirolimus seems to have poor activity in patients with progressive metastasized TCCU after failure of platinum containing first-line therapy.

Vinflunine: a fluorinated vinca alkaloid for bladder cancer therapy.

Vinflunine is a novel third-generation bifluorinated semisynthetic vinca alkaloid that has been shown to have activity against a variety of solid tumor types including advanced transitional cell carcinoma of the urothelium. In contrast to other vinca alkaloids, vinflunine shows superior antitumor activity and an excellent safety profile. Vinflunine interacts with tubulin and has a lower affinity to tubulin; it has a high intracellular accumulation rate and therefore significant effects on microtubule dynamics. A large, phase III trial comparing vinflunine with best supportive care versus best supportive care alone showed an improvement in overall survival in the vinflunine arm in preplanned secondary analyses. In addition, the drug has shown a moderate adverse event profile in the phase II and III trials. In September 2009, vinflunine was approved as a second-line treatment for patients with urothelial carcinoma resistant to first-line platinum-containing chemotherapy by the European Medicines Agency.

mTOR-inhibition in metastatic renal cell carcinoma. Focus on temsirolimus: a review.

The potent inhibitor of the mammalian target of rapamycin, temsirolimus, comprises for cell cycle, angiogenesis and proliferation and has proven beneficial in the treatment of advanced renal cell carcinoma (RCC). Temsirolimus is officially approved for first line therapy in high risk previously untreated mRCC patients. This review summarizes the current clinical role of temsirolimus in the treatment of advanced renal cell carcinoma with regard to pharmacological features, toxicity and tolerability. It particularily discusses quality of life issues as important outcome parameters in palliative treatment of patients with mRCC and gives an outlook on current clinical developments regarding possible future combining/ sequencing strategies of temsirolimus.

What happens if nothing happens?--History of an untreated urothelial carcinoma of the bladder.

UNLABELLED: Bladder cancer is controllable when adequately diagnosed and treated according to current recommendations. Radical cystectomy with urinary diversion is the standard therapy for muscle invasive tumors. In patients unfit or unwilling to get radical surgery, external beam or combined chemo-radiotherapy display alternative treatment options and can be safely performed. Every therapy implies the patient's disposition to cooperate. CASE PRESENTATION: This case report describes the clinical course over 31 months after initial diagnosis of a 56-years-old Caucasian, white man with an initial pT1G3 urothelial carcinoma of the bladder. The patient denied early radical cystectomy, radio-chemotherapy and almost all alternative treatment possibilities. He finally died 31 months after initial verification of the disease.

Gemcitabine, paclitaxel, and cisplatin as combined adjuvant approach in transitional cell carcinoma of the urothelium.

AIM: The objective of this study was to evaluate the adjuvant chemotherapy with gemcitabine, paclitaxel, and cisplatin for urothelial carcinoma. METHODS: Twenty-seven patients with invasive transitional cell carcinoma of the urothelium were treated between 2001 and 2007. All patients received chemotherapy with intravenous gemcitabine at a dose of 1000 mg/mC on Days 1 and 8, intravenous paclitaxel at a dose of 80 mg/mC on Days 1 and 8, and intravenous cisplatin at a dose of 50 mg/mC on Day 2. Treatment courses were repeated every 21 days. RESULTS: Median follow-up period was 32.5 months. Six patients came to progressive disease. The median overall survival was not reached, and the actuarial 1-year and 2-year survival rates were 89% and 67% respectively. The median progression-free survival was 10.0 months. Median survival time for patients with ECOG status 0, and 1 was 52.0, and 22.0 months respectively. Grade 4 neutropenia occurred in 18.5% of patients, but there was no treatment related mortality. CONCLUSIONS: The combination of gemcitabine, paclitaxel, and cisplatin is a highly effective and tolerable regimen for patients with invasive transitional cell carcinoma of the urothelium. This treatment should be considered as a suitable option that deserves further prospective evaluation. ECOG performance status is an important predictive factors for survival.

Palliative chemotherapy with gemcitabine, paclitaxel, and cisplatin as first-line treatment following gemcitabine monotherapy for patients with transitional cell carcinoma of the urothelium.

AIM: Chemotherapeutic agents are active in transitional cell cancer of the urothelium, and combinations have shown promising results. The objective of this study was to evaluate the palliative chemotherapy with gemcitabine, paclitaxel, and cisplatin for transitional cell carcinoma. METHODS: Thirty-four patients with advanced transitional cell carcinoma of the urothelium were treated between 2000 and 2007. All patients received chemotherapy with intravenous gemcitabine at a dose of 1000 mg/m2 on days I and VIII, intravenous paclitaxel at a dose of 80 mg/m2 on days I and VIII, and intravenous cisplatin at a dose of 50 mg/m2 on day II. Treatment courses were repeated every 21 days. After completion of four to six courses in this regimen an application of intravenous gemcitabine at a dose of 1000 mg/m2 followed repeating every 28 days. RESULTS: Twelve patients (35.3%) had 1 visceral sites of metastases. Twenty two patients (64.7%) had achieved objective responses to treatment (29.4% complete responses). The median actuarial survival was 18.5 months, and the actuarial one-year and two-year survival rates were 56% and 26% respectively. After a median follow-up of 16.3 months, 18 patients remained alive. The median progression-free survival was 7 months. Median survival time for patients with ECOG status 0, 1, and 2 was 45, 12, and 10.5 months respectively. Grade 3-4 neutropenia occurred in 41.2% of patients. CONCLUSIONS: The combination of gemcitabine, paclitaxel, and cisplatin is a highly effective and tolerable regimen for patients with advanced transitional cell carcinoma of the urothelium. This treatment should be considered as a suitable option that deserves further prospective evaluation. ECOG performance status and visceral metastases are important predictive factors for survival.

Temsirolimus in renal cell carcinoma.

Patients with metastatic renal cell carcinoma (RCC) generally show a poor prognosis; treatment approaches have not significantly improved patient survival. Temsirolimus inhibits the mammalian target of rapamycin kinase. Clinical studies have shown positive results when the drug is administered to patients with this disease. The clinical benefit of temsirolimus for poor-risk, advanced RCC patients was demonstrated in a Phase III study comparing temsirolimus with interferon alpha (IFN-alpha) or combined temsirolimus plus IFN-alpha as first-line treatment of advanced RCC, showed that treatment with temsirolimus alone significantly increased median overall survival in poor-risk, advanced RCC patients (10.9 vs 7.3 vs 8.4 months). This was the first Phase III trial to demonstrate an overall improvement in survival using an agent as "targeted therapy" for patients with advanced RCC. By November 2007, 200 patients with advanced RCC had been treated with temsirolimus before its approval by the European Medicines Agency (EMEA) within a compassionate use program. The single-center treatment experiences using temsirolimus in patients for compassionate use are described herein. The treatment was generally well tolerated; side effects (mucositis, diabetes, and peripheral edema) were within the range expected from the pivotal trials and manageable with supportive care. Further development strategies for temsirolimus in patients with RCC include its evaluation with bevacizumab and also as second-line therapy in patients who have failed first-line therapy with sunitinib.