Imaging studies in metastatic urogenital cancer patients undergoing systemic therapy: recommendations of a multidisciplinary consensus meeting of the Association of Urological Oncology of the German Cancer Society.

INTRODUCTION: Imaging studies are an integral and important diagnostic modality to stage, to monitor and follow-up patients with metastatic urogenital cancer. The currently available guidelines on diagnosis and treatment of urogenital cancer do not provide the clinician with evidence-based recommendations for daily practice. OBJECTIVES: To develop scientifically valid recommendations with regard to the most appropriate imaging technique and the most useful time interval in metastatic urogenital cancer patients undergoing systemic therapy. METHODS: A systematic literature review was performed searching MedLine, Embase and Web of Science databases using the terms prostate, renal cell, bladder and testis cancer in combination with the variables lymph node, lung, liver, bone metastases, chemotherapy and molecular therapy, and the search terms computed tomography, magnetic resonance imaging and positron emission tomography were applied. A total of 11,834 records were retrieved from all databases. The panel reviewed the records to identify articles with the highest level of evidence using the recommendation of the US Agency for Health Care Policy and Research. CONCLUSIONS: Contrast-enhanced computed tomography remains the standard imaging technique for monitoring of pulmonary, hepatic and lymph node metastases. Bone scintigraphy is still the most widely used imaging technique for the detection and follow-up of osseous lesions. For clinical trials it might be replaced by either PET-CT or MRI of the skeletal axis. Response assessment for patients treated with cytotoxic regime is best performed by the RECIST/WHO criteria; treatment response to molecular triggered therapy is best assessed by CT evaluating decrease in tumor size and density. Cross-sectional imaging studies for response assessment might be obtained after each 2 cycles of systemic therapy to early stratify responders from non-responders.

Therapy of local recurrence of renal cell carcinoma.

Local recurrence (LR) of renal cell carcinoma (RCC) after nephrectomy is a rare event with a poor prognosis. The clinical outcome of 15 patients with LR after tumor nephrectomy was analyzed retrospectively. Within a mean follow-up of 28 months (1-110 months) the mean time to recurrence (TTLR) was 23 months. Mean time to further tumor progression (TTP) after surgery was 22.2 months (11-32 months), after surgery and adjunctive therapy 6.8 months (3-15 months+) and after chemoimmunotherapy alone 3.6 months (3-6 months). Tumor specific survival (TSS) rate was 47% at 1 year and 33% at 3 years. Mean TSS after surgery was 62.2 months (38-110 months), after resection and adjunctive treatment 26 months (8-74 months) and after chemoimmunotherapy 9.2 months (7-15 months). In conclusion, surgery is recommended for treatment of LR. Additional benefit is not confirmed for any adjuctive therapy.

Regional thermoablation of local or metastatic renal cell carcinoma.

The objective of the study was to elucidate thermal based ablation techniques for local tumor control. Seven lesions of renal cell carcinoma (2 renal, 1 adrenal, 2 muscle, 1 hepatic, 1 bone) were treated under local (n=2) or general (n=6) anaesthesia with percutaneous cryoablation (CRA): CryoHit device or radiofrequency (RF) ablation (RFA): RF 3000). Treatment was palliative in 4 patients with progression after systemic therapies, and with curative intention in one organ confined tumor (patient with active HCV and HIV infection). Mean power for RFA was 165 watts. Duration of treatments was 10-91 min. No bleeding or urinary leakage was observed; no drainage or indwelling catheters necessary. Pain relief was sufficiently achieved by tramadol and novaminesulfon. Inpatient period on average was 4.25 days. CRA led to complete tumor destruction (CTD) of an adrenal mass (time to progression, 15+ months) and partial tumor destruction (PTD) of a lumbar lesion (19 months); RFA resulted in CTD of 3 lesions (liver, 9+ months; kidney, 1+, 13+ months) and PTD in 2 lesions (muscle and bone, 3 months). In conclusion, it was found that CRA and RFA are safe and effective methods to destroy metastatic RCC. Such minimal invasive techniques are favorable for palliative treatment (low performance status, surgical preconditions) and in conjunction with immunochemotherapy; A decreased risk of bleeding, the shorter duration of hospitalization and a faster recovery of the patient encourage minimal invasive percutaneous thermal based therapies due to life-quality and economic aspects. Treatment of primary renal cell carcinoma is currently under investigation.

The role of surgery in clinical management of patients with metastatic papillary renal cell carcinoma.

OBJECTIVES: Patients with metastatic papillary renal cell carcinoma (RCC) show special clinical behavior compared to patients with other histologic subtypes of RCC. This study aimed to assess the relevance of surgical and systemic options used in treatment of these patients prior to the recent era of targeted therapies. METHODS: Retrospectively, we assessed clinical data of 61 patients with metastatic papillary RCC who were treated at eight centers in Germany. RESULTS: Median follow-up was 20 (range 1-114) months and median age at time of diagnosis was 62 (range 24-85) years. Men were affected predominantly (50/61; 82%). Twenty-one patients (34%) showed metastases at time of diagnosis. In the remaining 40 patients, median time to development of metastases was 30.4 (range 3-143; mean 16.5) months. Sites of metastases were lung (37; 61%), bone (24; 38%), liver (20; 33%), lymph nodes (24; 38%), and local recurrence (17; 28%). Others sites of disease were brain metastases (6 patients/10%), peritoneal carcinosis (5 patients/8%), and others. A surgical approach with potentially curative intention was performed primarily in 11 patients (18%). 31 patients received an immuno- (interferon-alpha +/- interleukin-2) or immunochemotherapy as first line treatment for metastatic disease. Overall, 42/61 patients (69%) received systemic therapy. Supportive care only was performed in 12 patients (20%) because of poor performance status. Median overall survival after diagnosis of metastatic disease was longer than 48 months in patients with tumor resection (n = 11) compared to 13.0 +/- 4.3 months 95% CI 4.5-21.5 (n = 42) months in patients without surgical approach. CONCLUSIONS: Complete resection of metastases represents a valid option in management of patients with relapsing or metastatic papillary RCC.

Granulocyte colony-stimulating factor for the treatment of biomaterial-associated staphylococcal infections in-vitro.

Staphylococcal infections are a common and severe complication after the implantation of a prosthesis. We developed an in-vitro model for biomaterial-associated infections and studied the effects of human recombinant granulocyte colony-stimulating factor (rhuG-CSF; filgrastime) on the eradication of bacteria from the surface of biomaterial. Latex beads (25 micro m) were incubated with 10(7) colony forming units of either a slime producing (DSM 3269) or non-slime producing strain (ATCC 14990) of Staphylococcus epidermidis. Infected particles were consecutively confronted with effector cells, derived from heparinized whole blood samples taken from healthy volunteers, after stimulation with rhuG-CSF (5,000 IU/ml, 10,000 IU/ml). Control blood specimens were not stimulated or conditioned with normal saline. The results indicate that stimulation with rhuG-CSF induced an increased rate of phagocytosis and lead to a more rapid reduction of adhering bacteria from the surface of the beads. Therefore, the in-vitro data suggest that patients with prosthesis infection may profit from an additional treatment with rhuG-CSF.

All-trans retinoic acid and interferon-alpha for treatment of human renal cell carcinoma multicellular tumor spheroids.

INTRODUCTION: Conventional preclinical investigations have strongly recommended to combine interferon-alpha (IFN-alpha) with 13-cis retinoic acid (13-cRA, isotretinoin) for treatment of renal cell carcinoma (RCC). However, a recent randomized controlled trial on the drug combination ultimately failed to demonstrate an increased tumor-specific survival of patients with metastatic RCC (MRCC). All-trans retinoic acid (ATRA, tretinoin) was suggested to provide stronger antineoplastic properties than 13-cRA in different other tumors. MATERIALS AND METHODS: The present study aimed to compare ATRA with 13-cRA (0.1, 1, 10, 100 nM) alone or in combination with IFN-alpha (5, 400, 5,000, 25,000, 250,000 IU/ml) or 5-fluorouracil (5-FU; 0.1, 1, 10, 100 microg/ml). Multicellular tumor spheroids of human RCC cells (SN12C) were treated in order to facilitate the predictions of the model system. RESULTS: ATRA decreased the mean volume of SN12C spheroids 10-20% more than 13-cRA. Both retinoids led to a super-additive growth inhibition in combination with IFN-alpha, but not with 5-FU. However, in this scenario the superior effect of ATRA compared to 13-cRA, although statistically significant, was not impressive (<10%). CONCLUSIONS: ATRA provides a slightly stronger direct antineoplastic effect on human renal cancer cells than 13-cRA, and acts synergistically with IFN-alpha. However, ATRA, if at all, does not seem to be more suitable for treatment of patients with MRCC than 13-cRA.

Effect of augmentation cystoplasty on bone metabolism in chronic uremic rats.

PURPOSE: We examined the impact of urinary diversion using several types of intestinal segments on the bone metabolism of growing rats with renal insufficiency. MATERIALS AND METHODS: A total of 110, 8-week-old Sprague-Dawley rats underwent 2-stage subtotal nephrectomy by removal of 5/6 of the renal mass or sham operation. Except for a uremic control group all uremic rats underwent enterocystoplasty using stomach, ileum or colon. An additional group with colic augmentation received the bisphosphonate ibandronate. Bone mineral density of the tibia and lumbar spine, serum analysis and urinary excretion of the bone resorption marker deoxypyridinoline were determined monthly for 12 weeks. At study termination bone ash weight, bone mineral analysis and serum osteotropic hormone levels were determined. RESULTS: All groups undergoing subtotal nephrectomy had a decreased endogenous creatinine clearance of approximately 30%. The lowest gains in tibial and lumbar spine bone mineral density were observed in animals undergoing ileocystoplasty. Femoral calcium content was significantly decreased in uremic ileocystoplasty rats compared with uremic controls. These changes were not induced by alterations in serum pH, nor were they associated with accelerated bone resorption as assessed by deoxypyridinoline. Ibandronate prevented changes related to bone resorption and increased bone mass. CONCLUSIONS: Our results suggest that cystoplasty using ileum segments can aggravate renal bone disease in growing rats with mild uremia. Since the acid-base state was unchanged, other properties of the interposed ileum segment must be responsible for the negative effect on bone metabolism.