A multicenter paper-based and web-based system for collecting patient-reported outcome measures in patients undergoing local treatment for prostate cancer: first experiences.

PURPOSE: To give an overview of the multicenter Prostate Cancer Outcomes (PCO) study, involving paper-based and web-based collection of patient-reported outcome measures (PROM) in patients undergoing local treatment for prostate cancer in certified centers in Germany. The PCO study is part of the larger Movember-funded TrueNTH Global Registry. The article reports on the study's design and provides a brief progress report after the first 2 years of data collection. METHODS: Prostate cancer centers (PCCs) certified according to German Cancer Society requirements were invited to participate in collecting patient-reported information on symptoms and function before and at least once (at 12 months) after treatment. The data were matched with disease and treatment information. This report describes progress in patient inclusion, response rate, and variations between centers relative to online/paper use, and also data quality, including recruitment variations relative to treatment in the first participating PCCs. RESULTS: PCC participation increased over time; 44 centers had transferred data for 3094 patients at the time of this report. Patient recruitment varied widely across centers. Recruitment was highest among patients undergoing radical prostatectomy. The completeness of the data was good, except for comorbidity information. CONCLUSIONS: The PCO study benefits from a quality improvement system first established over 10 years ago, requiring collection and harmonization of a predefined clinical dataset across centers. Nevertheless, establishing a PROM routine requires substantial effort on the part of providers and constant monitoring in order to achieve high-quality data. The findings reported here may be useful for guiding implementation in similar initiatives.

Medication and Treatment Adherence Following Hospital Discharge.

BACKGROUND: Patients' drug regimens often need to be changed when they pass from one care sector to another, but these changes sometimes pose a safety risk. To avoid such risks, a new inter-sector transition concept was developed incorporating discharge medication plans and counseling modules for the patients themselves and the doctors receiving them into their care. METHODS: A prospective interventional trial was carried out in two internal medicine wards of a general hospital. After data acquisition from the control group, the transition concept was developed and evaluated in an independent intervention group. The discharge medication plan and the first post-discharge prescription were compared to identify patients who had at least one medication change that increased the post-discharge risk of either failure to achieve the therapeutic goal (category A, first endpoint) or of patient's lack of treatment adherence (category B). Gaps in care after discharge were also analyzed. RESULTS: 200 consecutive patients were enrolled in the trial. In the intention-to-treat analysis, the percentage of patients with potentially jeopardizing medication changes in category A declined from 54% (54/100) in the control group to 15% (15/100) in the intervention group. (p<0.001). For medication changes in category B, there was a corresponding decline from 53% (53/100) to 7% (7/100) (p < 0.001). Gaps in care were seen in 28% (28/100) of control patients and 18% (18/100) of patients in the intervention group (p = 0.031). CONCLUSION: The likelihood of a potentially jeopardizing medication change upon hospital discharge can be markedly reduced with the aid of a modular transition concept. Gaps in care can be closed in this way as well.

Non-invasive assessment of inter-and intrapatient variability of integrin expression in metastasized prostate cancer by PET.

PURPOSE: Due to the high expression of the integrin αvß3 not only on endothelial cells, but also on mature osteoclasts and prostate cancer cells, imaging of osseous metastases with αvß3-targeted tracers seems promising. However, little is known about the patterns of αvß3-expression in metastasized prostate cancer lesions in-vivo. Thus we evaluated the uptake of the αvß3-specific PET tracer [18F]Galacto-RGD for assessment of bone metastases in prostate cancer patients. RESULTS: [18F]Galacto-RGD PET identified 58/74 bone-lesions (detection rate of 78.4%) and lymph node metastases in 2/5 patients. The SUVmean was 2.12+/-0.94 (range 0.70-4.38; tumor/blood 1.36+/-0.53; tumor/muscle 2.82+/-1.31) in bone-lesions and 2.21+/-1.18 (range 0.75-3.56) in lymph node metastases. Good visualization and detection of bone metastases was feasible due to a low background activity of the surrounding normal bone tissue. METHODS: 12 patients with known metastasized prostate cancer according to conventional staging (including bone-scintigraphy and contrast-enhanced CT; median PSA 68.63 ng/ml, range 3.72-1935) were examined with PET after i.v.-injection of [18F]Galacto-RGD. Two blinded nuclear-medicine physicians evaluated the PET-scans in consensus concerning lesion detectability. Volumes-of-interest were drawn in the PET-scans over all metastases defined by conventional staging (maximum of 11 lesions/patient), over the left ventricle, liver and muscle and standardized-uptake-values (SUVs) were calculated. CONCLUSIONS: Our data show generally elevated uptake of [18F]Galacto-RGD in bone metastases from prostate cancer with a marked inter- and intrapatient variability. While [18F]Galacto-RGD PET is inferior to bone scintigraphy for detection of osseous metastases, it might be valuable in patient screening and monitoring of αvß3-targeted therapies due to the high variability of αvß3-expression.

Surgical management of penile fracture and long-term outcome on erectile function and voiding.

INTRODUCTION: Penile fracture is an emergency in urology. Surgical management is recommended, but objective data of postoperative long-term effects, especially regarding voiding and erectile function, vary. AIM: To assess long-term results of patients undergoing surgical therapy for penile fracture. METHODS: Patients presenting with suspicion of penile fracture were included in this study. Diagnosis of penile fracture was made by clinical assessment and surgery performed thereafter. The defect of the tunica albuginea was closed by absorbable suture. In case of concomitant urethral lesion, the defect was repaired simultaneously. Voiding and erectile function were evaluated at long-term follow-up by mail. Patients' status before penile fracture was assessed retroactively. MAIN OUTCOME MEASURES: Erectile function was assessed by the International Index of Erectile Function questionnaire and voiding function by the International Prostate Symptom Score questionnaire. RESULTS: N = 34 patients were included. Penile fracture was suspected in 28/34 (82.4%) patients. Twenty-six of the 28 (92.9%) patients underwent surgery. Only less than half of confirmed fracture patients presented with the classical triad of an audible crack, detumescense, and hematoma. Fourteen of the 26 (53.8%) patients after surgery were available for follow-up. Mean follow-up was 45.6 months (range: 3.6-128.4). In 13/14 (92.9%) patients, penile fracture was confirmed by surgery. At follow-up, 7/13 (53.8%) patients had impaired erectile function, with 3/13 (23.1%) patients needing medical treatment. Four of the 13 (30.8%) patients showed deterioration of voiding including occurrence of urethral fistula. CONCLUSIONS: Penile fracture is an emergency for which surgery should be offered. Clinical suspicion of fracture should be high even with hematoma alone. Concomitant urethral injury is common, particularly with bilateral corporal rupture and/or initial hematuria. Preoperative counseling should include discussion of long-term erectile and voiding dysfunction, penile deformity, and urethral fistula both with and without surgery. Close patient follow-up is required.

Positive effects of zoledronate on skeletal-related events in patients with renal cell cancer and bone metastases.

INTRODUCTION: Approximately 30% of patients with renal cell cancer (RCC) develop bone metastasis causing skeletal-related events (SRE): pathologic fracture, spinal cord compression, surgery to bone and radiotherapy. Zoledronic acid demonstrated significant clinical benefit in RCC patients in a retrospective analysis. Primary objective of this prospective study was the proportion of patients experiencing ≥ 1 SRE during 12 months of zoledronic acid treatment and to verify the retrospective data. MATERIALS AND METHODS: Fifty patients with histologically confirmed RCC and evidence of ≥ 1 cancer-related bone lesion and ≤ 3 prior bisphosphonate applications were enrolled in 19 German centers between 2004 and 2007. The patients received 4 mg zoledronic acid every 3 weeks for 12 months followed by a follow up period for overall survival of 12 months. Bone lesions were diagnosed by bone scan or MRI-quickscan. Greater and equal to 1 lesion had to be confirmed by x-ray, CT or MRI scan. Additional bone scans were performed after completion of study treatment and if clinically indicated. In case of suspicion or evidence of a SRE it had to be confirmed radiologically. RESULTS: In total, 49 of the 50 enrolled patients were treated. Only 11 of them (22.4%) experienced any SRE until month 12. Patients with > 6 lesions and higher baseline MSKCC (Memorial Sloan-Kettering Cancer Center) score had a higher risk for SREs. Zoledronic acid was generally well tolerated and its known safety profile was affirmed. CONCLUSIONS: This prospective study confirms the results of prior data about the efficacy of zoledronic acid in patients with metastatic (m)RCC, supporting its beneficial use in these patients.

Chemotherapeutic drugs sensitize human renal cell carcinoma cells to ABT-737 by a mechanism involving the Noxa-dependent inactivation of Mcl-1 or A1.

BACKGROUND: Human renal cell carcinoma (RCC) is very resistant to chemotherapy. ABT-737 is a novel inhibitor of anti-apoptotic proteins of the Bcl-2 family that has shown promise in various preclinical tumour models. RESULTS: We here report a strong over-additive pro-apoptotic effect of ABT-737 and etoposide, vinblastine or paclitaxel but not 5-fluorouracil in cell lines from human RCC. ABT-737 showed very little activity as a single agent but killed RCC cells potently when anti-apoptotic Mcl-1 or, unexpectedly, A1 was targeted by RNAi. This potent augmentation required endogenous Noxa protein since RNAi directed against Noxa but not against Bim or Puma reduced apoptosis induction by the combination of ABT-737 and etoposide or vinblastine. At the level of mitochondria, etoposide-treatment had a similar sensitizing activity and allowed for ABT-737-induced release of cytochrome c. CONCLUSIONS: Chemotherapeutic drugs can overcome protection afforded by Mcl-1 and A1 through endogenous Noxa protein in RCC cells, and the combination of such drugs with ABT-737 may be a promising strategy in RCC. Strikingly, A1 emerged in RCC cell lines as a protein of similar importance as the well-established Mcl-1 in protection against apoptosis in these cells.

Amplification of epidermal growth factor receptor gene in renal cell carcinoma.

Expression of epidermal growth factor receptor (EGFR) may be of prognostic value in renal cell cancer (RCC). Gene amplification of EGFR was investigated in a cohort of 315 patients with advanced RCC from a previously reported randomised study. Using fluorescent in situ hybridisation, only 2 patients (0.6%) had gene amplification; therefore gene amplification is of no prognostic value in RCC.

Vaginal carcinoma in a female-to-male transsexual.

INTRODUCTION: Sex reassignment surgery (SRS) can be considered a reasonable and secure treatment for transsexualism, today. Because the population of patients who have received SRS is growing steadily, it can be expected that the number of patients who present with diseases specific to their original gender will increase as well. AIM: In female-to-male transsexuals, vaginal cancer has not been reported so far. This article reports, to our knowledge, the first case of a female-to-male transsexual who developed vaginal cancer. METHODS: Eighteen years after receiving female-to-male SRS, the patient presented with vaginal cancer, which infiltrated rectum and bladder and also showed involvement of inguinal lymph nodes. Surgery consisted of an anterior and posterior pelvic demolition and extended lymphadenectomy with preservation of the penoid and reconstruction of the pelvic defect with multiple flaps. RESULTS: The tumor was removed completely (R0), and 2 years after surgery, the patient has no signs or symptoms of tumor recurrence and enjoys good quality of life. CONCLUSIONS: In SRS patients, diseases of their original gender should always be considered and patients should be encouraged to participate in screening programs. When choosing the surgical approach for SRS, the risks for developing cancer from remaining structures of the genetic gender should be considered. Of course, removal of e.g., ovaries, cervix and vagina, will prevent cancer of these structures. When it comes to surgery in SRS patients with malignancies, an interdisciplinary approach should be chosen.

Influence of body mass index on operability, morbidity and disease outcome following radical cystectomy.

INTRODUCTION: Obesity may influence postoperative outcome after tumor surgery. We evaluated the impact of patients' body mass index (BMI) on peri- and postoperative morbidity and outcome following radical cystectomy for bladder cancer. PATIENTS AND METHODS: 390 consecutive patients who underwent radical cystectomy due to bladder cancer from January 1986 to December 2004 were reviewed. According to WHO criteria, patients were divided into normal weight (NW, 45.6%), overweight (OW, 44.4%) and obese (10.0%) subgroups. The BMI of patients was associated to the time of surgery, amount of intraoperative blood units, TNM stage, postoperative complication rate as well as overall survival. RESULTS: The time of cystectomy increased with the degree of patients' obesity (NW, 330 min; OW, 355 min; p = 0.007). Between NW and OW patients no significant differences were noted in respect to intraoperative blood transfusion rate (NW, 3.0; OW, 2.0; p = 0.47), postoperative TNM stage (pTis-pT2b: 42.6 vs. 48.6%; pT3a-4: 38.2 vs. 27.2%; pN+: 20.2 vs. 24.2%) and postoperative complications, except for postoperative bleeding, which was more common in OW patients (p = 0.02). Mean overall survival times showed no significant differences between NW and OW patients receiving ileal conduits (5-year survival rate: 34.0 vs. 41.1%; p = 0.140) or ileal neobladders (5-year survival rate: 65.1 vs. 70.8%; p = 0.127). CONCLUSIONS: Increased BMI poses a greater challenge for surgical interventions such as radical cystectomy in bladder cancer patients. However, in our series, intra- and postoperative morbidity was not significantly elevated in OW patients. Overall survival was not reduced in OW compared to NW patients. Therefore, elevated BMI is not an exclusion criterion for radical cystectomy in bladder cancer patients.

Lapatinib versus hormone therapy in patients with advanced renal cell carcinoma: a randomized phase III clinical trial.

PURPOSE: Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2. PATIENTS AND METHODS: Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number of metastatic sites--were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses. RESULTS: Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT (hazard ratio [HR] = 0.94; P = .60), and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT (HR = 0.88; P = .29). In a biomarker analysis of patients with EGFR-overexpressed tumors (3+ by immunohistochemistry [IHC]; n = 241) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT (HR = 0.76; P = .06), and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT (HR = 0.69; P = .02). These results were confirmed by Cox regression analysis. No unexpected toxicities were observed; the most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhea (40%). CONCLUSION: Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC.

Comparison of 16-MDCT and MRI for characterization of kidney lesions.

OBJECTIVE: The objective of our study was to compare the diagnostic performance of 16-MDCT with that of MRI in the characterization of kidney lesions. SUBJECTS AND METHODS: Twenty-eight patients with kidney lesions detected with sonography and requiring further evaluation were examined. MDCT was performed in the unenhanced, arterial, and portal venous phases. MRI was performed at 1.5 T with T2- and T1-weighted and dynamic gadolinium-enhanced sequences. Consensus reading was done by two radiologists. Image quality was rated on a four-point scale. Classification of lesions as surgical or nonsurgical was done with five levels of confidence, and it was required that a definite diagnosis be assigned to each lesion. The 1997 TNM classification was used for staging. Statistical analysis was done by receiver operating characteristic analysis or paired Student's t test. Histologic or follow-up findings at least 12 months after the primary diagnosis served as the standard of reference. RESULTS: The image quality of MDCT (mean grade, 2.79 on a 0-3 scale) was superior to that of MRI (1.93; p < 0.01). The area under the curve for differentiating surgical from nonsurgical lesions was 0.979 for MDCT and 0.957 for MRI with resulting sensitivity and specificity values of 92.3% and 96.3% for MDCT and 92.3% and 91.3% for MRI. Sensitivity and specificity for definite classification of the lesions were 93.8% and 68.4% for MDCT and 93.8% and 71.4% for MRI. CONCLUSION: Both MDCT and MRI are excellent for differentiating surgical from nonsurgical kidney lesions. Both methods have low specificity for the differentiation of benign from malignant lesions.

MR cystography for bladder tumor detection.

The purpose of the study was to assess the diagnostic performance of MR cystography with virtual cystoscopic and multiplanar reconstructions for detection of malignant bladder tumors. Thirty-two patients with 43 bladder tumors previously confirmed by cystoscopy (mean size 2.5 cm; 0.4-9.1 cm;) were examined at 1.5 T with a three-dimensional T2-weighted turbo spin echo sequence (TR=2911 ms, TE=500 ms, echo train length 256). Virtual cystoscopic reconstructions (VC) and multiplanar reconstructions (MPR) were obtained and analyzed separately by three radiologists without knowledge of the tumor location. Intraoperative or cystoscopic findings served as standard of reference. Sensitivities and specificities were calculated using a receiver-operating characteristic analysis with five levels of confidence. Area-under-curve values were similar for MPRs (0.952), VC (0.932) and the combination of both methods (0.954). Optimal sensitivity was 92.3% for MPR and 90.7% for VC, respectively, with a specificity of 91.1% for MPR and 90.4% for VC. The combination of MPR and VC resulted in a sensitivity of 90.7% and specificity of 94.0%. MR cystography is a promising, completely non-invasive technique for the detection of bladder lesions with a high diagnostic performance.