Effect of different optimization parameters in single isocenter multiple brain metastases radiosurgery.

PURPOSE: Automated treatment planning for multiple brain metastases differs from traditional planning approaches. It is therefore helpful to understand which parameters for optimization are available and how they affect the plan quality. This study aims to provide a reference for designing multi-metastases treatment plans and to define quality endpoints for benchmarking the technique from a scientific perspective. METHODS: In all, 20 patients with a total of 183 lesions were retrospectively planned according to four optimization scenarios. Plan quality was evaluated using common plan quality parameters such as conformity index, gradient index and dose to normal tissue. Therefore, different scenarios with combinations of optimization parameters were evaluated, while taking into account dependence on the number of treated lesions as well as influence of different beams. RESULTS: Different scenarios resulted in minor differences in plan quality. With increasing number of lesions, the number of monitor units increased, so did the dose to healthy tissue and the number of interlesional dose bridging in adjacent metastases. Highly modulated cases resulted in 4-10% higher V10% compared to less complex cases, while monitor units did not increase. Changing the energy to a flattening filter free (FFF) beam resulted in lower local V12Gy (whole brain-PTV) and even though the number of monitor units increased by 13-15%, on average 46% shorter treatment times were achieved. CONCLUSION: Although no clinically relevant differences in parameters where found, we identified some variation in the dose distributions of the different scenarios. Less complex scenarios generated visually more dose overlap; therefore, a more complex scenario may be preferred although differences in the quality metrics appear minor.

Robotic Salvage Lymph Node Dissection in Recurrent Prostate Cancer: Lessons Learned from 68 Cases and Implications for Future Clinical Management.

PURPOSE: Salvage lymph node dissection is a rescue treatment for patients with nodal recurrence after radical prostatectomy. Very limited data are available on robotic salvage lymph node dissection. Our purpose was to investigate perioperative and oncological outcomes of robotic salvage lymph node dissection in a large monocentric series. MATERIALS AND METHODS: Perioperative data, complications within 30 days after surgery and oncological outcomes as assessed by histology, prostate specific antigen changes, prostate specific antigen nadir after salvage lymph node dissection, and time to further therapy were analyzed. To identify predictive factors for oncological outcome, Kaplan-Meier and Cox-regression analyses were performed. For cases with a mismatch between preoperative positron emission tomography/computed tomography and the number of histologically positive lymph nodes, prostate specific membrane antigen immunohistochemistry was performed on removed lymph nodes. RESULTS: A total of 68 patients underwent robotic salvage lymph node dissection with a median operation time of 126 minutes, a blood loss of 50 ml, and a length of stay of 4 days. No major complications (>Clavien 3) occurred. Median followup was 12.1 months. Median time to further therapy was 12.4 months, 37% of patients experienced complete biochemical response (prostate specific antigen <0.2 ng/ml) and 11% reached an undetectable prostate specific antigen, which was maintained for >1 year in 3 cases. Lower preoperative prostate specific antigen, longer time between radical prostatectomy and salvage lymph node dissection, preoperative prostate specific membrane antigen positron emission tomography/computed tomography and complete biochemical response after salvage lymph node dissection were significant predictors of longer therapy-free survival (all p <0.005). Prostate specific membrane antigen immunohistochemistry revealed that prostate specific membrane antigen positron emission tomography/computed tomography tends to miss small lymph node metastases <5 mm. CONCLUSIONS: Robotic salvage lymph node dissection is a feasible approach with low perioperative morbidity and delays further systemic therapy in most patients. Prostate specific membrane antigen positron emission tomography/computed tomography detection is mostly limited to tumor foci >5 mm.

New insights in the paradigm of upregulation of tumoral PSMA expression by androgen receptor blockade: Enzalutamide induces PSMA upregulation in castration-resistant prostate cancer even in patients having previously progressed on enzalutamide.

PURPOSE: There is preliminary evidence for prostate-specific membrane antigen (PSMA) upregulation effects of androgen receptor blockade in prostate cancer. In an attempt to find the best condition for PSMA radioligand therapy in metastatic castration-resistant prostate cancer (mCRPC) patients, we evaluated the effect of oral enzalutamide in patients, predominantly having previously progressed on enzalutamide treatment. METHODS: Ten patients with advanced mCRPC scheduled for PSMA radioligand therapy were examined with 68Ga-PSMA-11 PET/CT before and after a mean of 11.8 days of enzalutamide 160 mg/day. Imaging results were compared using total PSMA tumor burden quantification. We assessed whole-body total lesion PSMA (TLP), defined as SUVmean × tumor volume and calculated TLP-to-liver ratio (TLP-LR), TLP-to-parotid gland ratio (TLP-PR), and TLP-to-kidney ratio (TLP-KR). RESULTS: The mean (median) increase of TLP-LR, TLP-PR, and TLP-KR in the cohort was 49.3% (38.8%), 45.1% (23.5%), and 54.9% (37.6%), respectively. These increases were statistically significant (p = 0.002, p = 0.014, and p = 0.014), while PSA values did not change significantly (p = 0.846). Seven of the 10 patients had previously undergone enzalutamide treatment with eventual progression, formally classified as treatment failure. No side effects were noted in the short term. CONCLUSIONS: Our results suggest that enzalutamide could be considered as a PSMA radioligand treatment enhancing primer medication, which may increase PSMA expression by a dimension of 50% in mCRPC. The effect was shown even in patients having previously failed enzalutamide treatment for arrest of progression in the mCRPC setting. Our observation deserves evaluation in a prospective setting.

Guideline adherence in bone-targeted treatment of cancer patients with bone metastases in Germany.

PURPOSE: To assess adherence to the current European Society for Medical Oncology (ESMO) clinical practice guideline on bone health in cancer patients and the German guidelines for lung, breast, and prostate cancer among German oncologists in hospitals and office-based physicians and to identify predictors of guideline compliance to assess the needs for dedicated training. METHODS: This was a retrospective sample analysis representing hospitals and office-based physicians in Germany in 2016. Records from lung, breast, and prostate cancer patients who had received a diagnosis of bone metastasis between April 1, 2015, and March 31, 2016, were included. Oncologists at participating centers answered a self-assessment survey on aspects related to their professional life, including guideline adherence and years of clinical experience in medical oncology. Guideline adherence rates were assessed from patient records. Treatment variables and survey data were used to identify predictors of guideline compliance in a Classification and Regression Tree (CART) analysis. RESULTS: Disregarding recommendations for supplementation of calcium and vitamin D, guideline adherence among physicians treating lung, breast, or prostate cancer patients was 62%, 92%, and 83%, respectively. Compliance was 15%, 42%, and 40% if recommendations for dietary supplements were taken into account. Identified predictors of guideline compliance included treatment setting, medical specialty, years of professional experience, and frequency of quality circle attendance. CONCLUSIONS: Compliance with the ESMO and the German guidelines in cancer patients varies between medical specialties. In particular, patients with lung cancer and bone metastases often do not receive the recommended osteoprotective treatment and required supplementation. Discrepancies between guideline recommendations and common practice should be addressed with dedicated training.

Radical prostatectomy in T4 prostate cancer after inductive androgen deprivation: results of a single-institution series with long-term follow-up.

OBJECTIVES: To determine the outcomes of complete surgical resection of T4 prostate cancer after inductive androgen-deprivation therapy (ADT), as inductive ADT and subsequent radical prostatectomy (RP) is not recommended by any guideline yet. PATIENTS AND METHODS: A monocentric RP database was queried for patients initially diagnosed with T4 prostate cancer, considered primarily as inoperable because of a fixed mass defined by rectal examination in combination with high PSA level and/or large foci of biopsy confirmed undifferentiated prostate cancer. Treatment consisted of primary ADT until PSA nadir with consecutive RP. Patients underwent retropubic RP (RRP) or robot-assisted laparoscopic RP (RALP) after inductive ADT until achievement of the PSA nadir, which is in general reached after 6-7 months. The intraoperative course and complications were analysed. Finally, Kaplan-Meier estimates were calculated for overall survival (OS) and prostate cancer-specific survival (PCSS). RESULTS: We retrospectively identified 116 patients treated between 2000 and 2014. At diagnosis, the median (range) PSA level was 37.6 (2.44-284) ng/mL. The preoperative median (range) PSA after inductive ADT was 0.73 (0.01-34) ng/mL. Thereafter, patients underwent RRP or, since 2006, RALP. The median (95% confidence interval) OS was 156 (118.9-193.1) months. The PCSS at 150 months was 82%. CONCLUSIONS: Surgical therapy of primarily inoperable prostate cancer is feasible and safe after inductive ADT. The OS of this cohort seems comparable with results described for patients with primary operable high-risk prostate cancer.

Kidney autotransplantation after nephrectomy and work bench surgery as an ultimate approach to nephron-sparing surgery.

BACKGROUND: Kidney autotransplantation (KAT) is the ultimate approach for nephron-sparing surgery. It is a rarely used method in renal tumor surgery today as minimal invasive and open techniques for nephron-sparing surgery improve constantly. In this publication, the complication rate and the long-term functional and oncological outcome at a single center are analyzed. METHODS: A prospectively constructed database of patients with renal tumors who underwent renal surgery was retrospectively analyzed to identify patients with KAT and describe surgical and oncological outcomes and to obtain long-term follow-up. Data collection included detailed surgical technique, complications (Clavian-Dindo), and hospital stay, as well as functional and oncological outcome and long-term follow-up. RESULTS: Between 1976 and 2013, 12 patients (median age 50.5 years) underwent KAT for highly complex renal masses: in five cases for complex renal cell carcinoma (RCC), five cases for complex upper urinary tract carcinoma (UTUC), one case for a renal metastasis, and one case for nephroblastoma. The nephrectomy or nephron-ureterectomy was performed open via a flank or transabdominal. The median surgical time was 360 min (range 270-490 min). Intraoperatively, six cases required blood transfusions (50%). Six patients (50%) developed significant postoperative complications (Clavian-Dindo > 2). In two patients, intermittent hemodialysis for delayed graft function (16.6%) was needed, and in six cases (50%), additional blood transfusions postoperatively were necessary. At discharge from hospital, all patients had functioning grafts. The median hospital stay was 29.5 days (range 18-35). At follow-up (median follow-up of 83.5 ± 40.7 months), six patients had died (50%)-all with functioning grafts (free from hemodialysis). In five cases, recurrence of primary tumor or metastatic disease was recorded. In four cases, the recurrent carcinoma could be resected; in detail, UTUC in three cases and one partial nephrectomy of the autotransplanted kidney was performed. One patient suffered from bone and lung metastasis. Two patients died finally tumor-related. Five patients (41.6%) are presently alive, without evidence of tumor relapse. One patient developed terminal renal failure requiring hemodialysis 105 months after autotransplantation. One additional patient was lost to follow-up; after 69 months, this patient had a functioning kidney and no evidence of disease-recurrence at the last follow-up. A cumulative number of 1424 months without hemodialysis was gained for these 12 patients. In the literature to date, most KAT are performed in benign disease, with minor but frequent complication. Here, we report the largest series of KAT for malignant kidney tumors. The complication rates are similar, compared to the recently reported series for benign indications with an improved graft survival rate. Since KAT requires a complex and challenging surgical approach, it should be performed by experienced kidney transplant surgeons. CONCLUSION: In very complex cases involving renal tumors and multi-morbidity, patients should be counseled well before KAT is considered. At the same time, KAT should not be abandoned in these very rare cases, especially when a nephron-sparing approach is otherwise not feasible. KAT can maintain renal function and quality of life and extend expectancy of life.

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer.

INTRODUCTION: We evaluated the efficacy and tolerability of 3- and 6-month leuprorelin acetate (LA) depot formulations (Eligard®, Astellas Pharma GmbH) in patients with advanced prostate cancer treated in routine clinical practice in Germany. MATERIALS AND METHODS: Data was pooled from 2 prospective, open-label, non-interventional studies in which 1,906 patients were treated for 12 months with either the 3-month (n = 633) or 6-month (n = 1,273) LA formulation. RESULTS: Median prostate-specific antigen levels in the pooled patient population declined from 12.0 ng/mL at baseline to 0.5 ng/mL after 12 months. Prostate-specific antigen reduction was achieved in treatment-naïve and pre-treated patients. Adverse events were documented in 8.8% of patients. CONCLUSIONS: These pooled data from routine clinical practice in Germany indicate that LA 3- and 6-month depot injections can effectively reduce prostate-specific antigen levels in a broad patient population with advanced prostate cancer.

Segmental Testicular Infarction: Case Series and Literature Review of a Rare Diagnosis in Men with Acute Testicular Pain.

The incidence of segmental testicular infarction (STI) is very low. Such a disorder most often affects young men. The most common symptom is sudden testicular pain. We report 6 cases of men diagnosed with STI. Clinical examination, blood test, urine analysis, and ultrasound examination with colour Doppler were performed. Furthermore, tissue sonoelastography or MRI was performed in selected patients. All men underwent surgical exploration. In all but one man, the affected testis was preserved. Although STI is a rare condition, it should be taken into account if testicular pain prior to suspicious ultrasound imaging occurs. To be aware of this benign testicular pathology and its clinical and imaging features is important to avoid unnecessary orchiectomies in young patients.

Organ-Preserving Surgical Treatment of a Horseshoe Kidney Occupied by a Large Renal Cell Carcinoma with Extensive Venous Invasion: A Case Report.

The horseshoe kidney is one of the most common congenital disorders affecting the urogenital system. Following a fusion of the lower kidney poles, which in turn lead to the formation of an isthmus, this anatomical variation is accompanied by other characteristic properties like an incomplete ascension, ventral rotation of the pelvices as well as atypical vascular supply. Even though renal carcinoids and Wilms tumors are more common in horseshoe kidneys, the incidence of renal cell carcinomas seems to be unaffected. Here we report the case of a locally advanced renal cell carcinoma with extensive venous invasion occurring in a horseshoe kidney and its complex surgical management. The whole primary tumor as well as a majority of venous tumor thrombi could be removed by a combination of 2/3 nephrectomy and cavotomy with thrombectomy. During 1 year of follow-up, the patient neither suffered from a tumor relapse, nor did he require renal replacement therapy. Thus, we conclude that even in cases of RCC where advanced disease is associated with complex anatomical situations, organ-preserving surgical treatment should be pursued to achieve excellent functional and oncological results.

Robot-assisted vs open adrenalectomy: evaluation of cost-effectiveness and peri-operative outcome.

OBJECTIVES: To compare robot-assisted laparoscopic adrenalectomy (RALA) and open adrenalectomy (OA) with regard to intra-operative complications, peri-operative outcome and cost effectiveness. SUBJECTS AND METHODS: Functional and statistical data from patients who underwent OA or RALA between 2001 and 2015 were prospectively recorded including intra- and postoperative outcomes. Data on per-day costs from current census reports (€540/day and €1 145/day for normal and intermediate care [IMC]) were also used to evaluate treatment costs. Additional costs for RALA were assumed at €2288 as reported in the current literature. Patients were matched by American Society of Anesthesiologists score, age, side of surgery and gender for comparison of OA and RALA. A total of 28 matched pairs were analysed with regard to patient characteristics, peri-operative outcomes and cost-effectiveness. Statistical significance of outcome variables was determined using Student's t-test and Pearson's chi-squared test. RESULTS: As a result of the matching process, patient groups did not differ in their main characteristics. Length of hospital stay was shorter for RALA than for OA (11.1 ± 4.8 vs 6.8 ± 1.2 days; P < 0.01) as was IMC treatment (2.3 ± 1.7 vs 1.2 ± 0.4 days; P < 0.01). The mean operating time was longer for RALA (128.5 ± 46.5 vs 102.2 ± 44.5 min; P = 0.03), but the last 10 RALA procedures (mean: 97.1 ± 35.2 min) were similar to OA. The rate of complications was similar in the two groups. Estimated costs were €8 627.5 for OA and €7 334 for RALA. CONCLUSIONS: The study showed that RALA was safe and cost-effective compared with OA. Increasing experience leads to similar operating times, putting high-volume centres at an advantage.

da Vinci and Open Radical Prostatectomy: Comparison of Clinical Outcomes and Analysis of Insurance Costs.

PURPOSE: To assess clinical outcomes and reimbursement costs of open and robotic-assisted radical prostatectomies in Germany. METHODS: Perioperative data of 499 open (2003-2006) and 932 (2008-2010) robotic-assisted radical prostatectomies as well as longitudinal reimbursement costs of an anonymized health insurance research database from Germany containing data of patients who underwent robotic-assisted or open radical prostatectomy were retrospectively analysed in a single-centre study. RESULTS: Significantly better outcomes after robotic-assisted vs. open prostatectomy were observed in regards to positive surgical margins (13.3 vs. 22.4%; p < 0.0001), intraoperative transfusions (0.1 vs. 2.6%; p < 0.0001), hospitalization (8.7 vs. 15.2 days; p < 0.0001) and duration of catheter (6.6 vs. 12.8 days; p < 0.0001). Operating time was significantly longer with robotic-assisted radical prostatectomy when compared to open surgery (184.4 vs. 128.0 min; p < 0.0001), while intraoperative complications showed a similar occurrence between both groups. Significant fewer postoperative complications were observed after robotic-assisted radical prostatectomy (26.5 vs. 42.5%; p < 0.0001) and rate of re-admission was lower for the robotic patients (13.6 vs. 19.4%; p = 0.0050). While insurance costs were higher in the 2 years before radical prostatectomy for the patients who underwent a robotic procedure (4,241.60 vs. 3,410.23 €; p = 0.202), additive costs of care of the year of surgery plus the 2 following years were less for the robotic cohort when compared to the costs incurred by the open group (21,673.71 vs. 24,512.37 €; p = 0.1676). CONCLUSIONS: The observed clinical advantages of robotic-assisted radical prostatectomy seem to result in reduced health insurance cost postoperatively when compared to open surgery. This should be taken into consideration regarding reimbursement and implementation of a clinically superior method.

Piwil 2 expression is correlated with disease-specific and progression-free survival of chemotherapy-treated bladder cancer patients.

Piwi-like 2 (Piwil 2) belongs to the family of Argonaute genes/proteins. The expression of Piwil 2 is associated with stem cells. A role in tumorigenesis and/or tumor progression is proposed for different cancers but not yet for bladder cancer (BCa). We investigated the Piwil 2 expression by immunohistochemistry in a cohort of 202 BCa patients treated by cystectomy and adjuvant chemotherapy. The association between Piwil 2 expression and disease-specific (DSS) or progression-free survival (PFS) was calculated using Kaplan Meier analyses and univariate/multivariate Cox's regression hazard models.In a multivariate Cox's regression, Piwil 2 expression, either in the cytoplasm or the nucleus, was significantly associated with DSS and PFS. A weak cytoplasmic staining pattern was associated with poor DSS and tumor progression (RR=2.7; P=0.004 and RR=2.4; P=0.027). Likewise,, absent nuclear Piwil 2 immunoreactivity was associated with poor DSS and tumor progression (RR=2.3; P=0.023 and RR=2.2; P=0.022). BCa patients whose tumors exhibited a combination of weak cytoplasmic and absent nuclear immunoreactivity had a 6-fold increased risk of tumor-related death (P=0.005) compared to patients with strong expression. Considering only patients with high grade G3 tumors, a 7.8-fold risk of tumor-associated death and a 3.6-fold risk of tumor progression were detected independently of the histologic tumor subtype or the chemotherapy regimen. In summary, a combination of weak cytoplasmic and absent nuclear expression of Piwil 2 is significantly associated with an increased risk of DSS and tumor progression. This implicates that Piwil 2 could be a valuable prognostic marker for high-risk BCa patients.

Second-Line Treatment of Advanced Urothelial Cancer with Paclitaxel and Everolimus in a German Phase II Trial (AUO Trial AB 35/09).

OBJECTIVE: The efficacy of second-line treatment after failure of platinum-based chemotherapy in patients with advanced urothelial cancer is limited. Based on encouraging preclinical and clinical phase I data, we evaluated the safety and efficacy of the combination of paclitaxel and everolimus in these patients. METHODS: In this trial, patients having failed to respond to prior platinum-based combination treatment of urothelial cancer were treated with paclitaxel (175 mg/m(2) i.v., 3-weekly) and the mTOR-inhibitor everolimus (10 mg p.o., once daily). The patients were treated until tumor progression or until a maximum of 6 cycles was completed. A one-stage design was used to evaluate the objective response rate (ORR) as the primary endpoint. RESULTS: A total of 27 patients (67% male; median age 63 years) were enrolled. The most frequent grade III/IV toxicities were anemia (28%), peripheral neuropathy (28%), and fatigue (24%). No treatment-related deaths were reported. Complete and partial remissions were observed in 0/24 and 3/24 patients eligible for efficacy analysis, respectively (ORR 13%). Progression-free survival was 2.9 months [95% confidence interval (95% CI) 1.9-4.2], and the median overall survival was 5.6 months (95% CI 4.8-10.2). CONCLUSION: The combination of paclitaxel and everolimus has not achieved the expected efficacy in second-line treatment of urothelial cancer and should not be further explored.

Quality of Preoperative Biopsy Is a Risk Factor for Positive Surgical Margins in Organ-Confined Prostate Cancer Treated with Nerve-Sparing Robot-Assisted Radical Prostatectomy.

PURPOSE: Positive surgical margins (PSM) during robot-assisted radical prostatectomy (RARP) negatively influence patients' prognosis. The aim of our study was to identify risk factors for PSM in patients with organ-confined prostate cancer (PCa). METHODS: A clinical database of all patients that underwent a RARP at our institution was used. Uni- and multivariable logistic regression analyses were conducted on the PSM rates for all patients with organ-confined PCa. RESULTS: Altogether, 1,600 patients were identified, including 1,085 organ-confined PCa with a PSM rate of 7.8%. On multivariable analysis, bilateral nerve-sparing (OR 3.025, 95% CI 1.587-5.765), surgeon volume <200 cases (OR 1.881, 95% CI 1.120-3.159) and a preoperative PSA >10 ng/ml (OR 3.674, 95% CI 1.379-9.796) remained independent prognostic factors. In a subgroup of patients undergoing a nerve-sparing RARP, the quality of the prostate biopsy (OR 2.398, 95% CI 1.325-4.341) was the sole independent risk factor for a PSM. CONCLUSION: An elevated preoperative PSA, surgical experience and a nerve-sparing procedure are all significantly associated with a higher risk for a PSM after RARP. For those undergoing a nerve sparing RARP, an accurate preoperative biopsy with detailed information on the location of positive cores is essential to prevent PSMs.

Sclerosing epithelioid fibrosarcoma of the kidney: clinicopathologic and molecular study of a rare neoplasm at a novel location.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare fibrosarcoma variant with specific histomorphology and consistent translocation (EWSR1-CREB3L1/2). To date, 110 cases have been reported; only 15 originated within the abdomen. With only 2 cases reported parallel to our study and one case briefly mentioned in a previous series, primary renal SEF is exceptionally rare but might be underrecognized. We herein describe 2 cases affecting a 23-year-old woman and a 43-year-old man. Tumor size was 22 and 4.2 cm, respectively. Patient 1 developed skeletal and multiple pulmonary metastases. She died of disease 82 months later, despite aggressive multimodality therapy. Patient 2 has no evidence of recurrence or metastasis (8 months after surgery). Histologic examination showed similar appearance with monotonous bland medium-sized epithelioid cells with rounded slightly vesicular nuclei and clear cytoplasm imparting a carcinoma-like appearance set within a highly sclerotic hyaline fibrous stroma. The tumor cells were arranged in nests, single cell cords, trabeculae, or solid sheets with frequent entrapment of renal tubules and glomeruli. Immunohistochemistry showed strong expression of vimentin, bcl2, CD99, and MUC4, whereas cytokeratin and other markers were negative. Fluorescence in situ hybridization showed a translocation involving the EWSR1 gene locus in case 2. Molecular analysis in case 1 was not successful due to poor signal quality. To our knowledge, this is the second report documenting primary renal SEF. Awareness of this entity would help avoid misinterpretation as clear cell carcinoma, sclerosing perivascular epithelioid cell tumor, Xp.11 translocation carcinoma, and other more frequent neoplasms at this site.

Is there an anti-androgen withdrawal syndrome for enzalutamide?

BACKGROUND: The anti-androgen withdrawal syndrome (AAWS) can be seen in one-third of patients after discontinuation of first-generation non-steroidal anti-androgen therapy. With the introduction of new agents for anti-androgen therapy as well as alternate mechanisms of action, new therapeutic options before and after docetaxel chemotherapy have arisen (Ohlmann et al. in World J Urol 30(4):495-503, 2012). The question regarding the occurrence of an enzalutamide withdrawal syndrome (EWS) has not been evaluated yet. In this study, we assess prostate-specific antigen (PSA) response after discontinuation of enzalutamide. METHODS: In total 31 patients with metastatic castration-resistant prostate cancer (mCRPC) underwent an enzalutamide withdrawal and were evaluated. Data were gathered from 6 centres in Germany. Patients with continuous oral administration of enzalutamide with rising serum PSA levels were evaluated, starting from enzalutamide withdrawal until subsequent therapy was initiated, follow-up ended or death of the patient occurred. Statistical evaluation was performed applying one-sided binomial testing using R-statistical software, version 3.0.1. RESULTS: Mean withdrawal follow-up was 6.5 weeks (range 1-26.1 weeks). None of the 31 patients showed a PSA decline. Mean relative PSA rise over all patients was 73.9 % (range 0.5-440.7 %) with a median of 44.9 %. CONCLUSIONS: If existent, an AAWS is at least very rare for enzalutamide in patients with mCRPC after taxane-based chemotherapy and does not play a clinical role in this setting. This may be attributed to the different pharmacodynamics of enzalutamide. Longer duration of therapy or a longer withdrawal interval may reveal a rare EWS in the future.

Long-term quality of life of testicular cancer survivors differs according to applied adjuvant treatment and tumour type.

PURPOSE: To evaluate the quality of life (QoL) in long-term testicular cancer (TC) survivors. METHODS: QoL was assessed in TC survivors treated between March 1976 and December 2004 (n = 625) using the EORTC-QLQ-C30 questionnaire, including a TC module. The assessment was performed at two time points (2006: response rate: n = 201/625 (32.2%), median follow-up (FU): 12.9 years (range 1.1-30.9); 2017: response rate: n = 95/201 (47.3%), median FU: 26.2 years (range: 13.0-41.2)). TC survivors were grouped according to treatment strategy, tumour entity, clinical stage and prognosis group. Linear and multiple linear regression analyses were performed, with age and time of follow-up as possible confounders. RESULTS: Radiation therapy (RT) compared to retroperitoneal lymph node dissection (RPLND) was associated with a higher impairment of physical function (2017: ß = - 9.038; t(84) = - 2.03; p = 0.045), role function (2017: ß = - 12.764; t(84) = - 2.00; p = 0.048), emotional function (2006: ß = - 9.501; t(183) = - 2.09; p = 0.038) and nausea (2006: ß = 6.679; t(185) = 2.70; p = 0.008). However, RT was associated with a lower impairment of sexual enjoyment (2017: symptoms: ß = 26.831; t(64) = 2.66; p = 0.010; functional: ß = 22.983; t(65) = 2.36; p = 0.021). Chemotherapy (CT), compared to RPLND was associated with a higher impairment of role (2017: ß = - 16.944; t(84) = - 2.62; p = 0.011) and social function (2017: ß = - 19.160; t(79) = - 2.56; p = 0.012), more insomnia (2017: ß = 19.595; t(84) = 2.25; p = 0.027) and greater concerns about infertility (2017: ß = 19.830; t(80) = 2.30; p = 0.024). In terms of tumour type, nonseminomatous germ cell tumour (NSGCT) compared to seminoma survivors had significantly lower impairment of nausea (2006: ß = - 4.659; t(187) = - 2.17; p = 0.031), appetite loss (2006: ß = - 7.554; t(188) = - 2.77; p = 0.006) and future perspective (2006: ß = - 12.146; t(175) = - 2.08; p = 0.039). On the other hand, surviving NSGCT was associated with higher impairment in terms of sexual problems (2006: ß = 16.759; t(145) = 3.51; p < 0.001; 2017: ß = 21.207; t(63) = 2.73; p = 0.008) and sexual enjoyment (2017: ß = - 24.224; t(66) = - 2.76; p = 0.008). CONCLUSIONS: The applied adjuvant treatment and the tumour entity had a significant impact on the long-term QoL of TC survivors, even more than 25 years after the completion of therapy. Both RT and CT had a negative impact compared to survivors treated with RPLND, except for sexual concerns. NSGCT survivors had a lower impairment of QoL compared to seminoma survivors, except in terms of sexual concerns. IMPLICATIONS FOR CANCER SURVIVORS: Implications for cancer survivors are to raise awareness of aspects of long-term and late effects on QoL in TC survivors; offer supportive care, such as psycho-oncological support or lifestyle modification, if a deterioration in QoL is noticed; and avoid toxic treatment without compromising a cure whenever possible.

Fast-track rehabilitation after robot-assisted laparoscopic cystectomy accelerates postoperative recovery.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: There is evidence from large abdominal surgeries and some open cystectomy series that multifactorial fast-track regimens shorten postoperative convalescence without any effect on morbidity and mortality. Such a regimen is of particular interest in combination with minimally invasive techniques, as early patient recovery demands for more rapid nutrition and mobilisation schemes. The present study, in a single institution, reports on the design, application and results of a fast-track protocol in patients undergoing robot-assisted laparoscopic cystectomy. There was no evidence of a higher incidence of complications with the fast-track regimen and postoperative recovery was faster. OBJECTIVES: To evaluate the feasibility and effectiveness of a multifactorial fast-track (FT) regimen on perioperative outcomes in patients undergoing robot-assisted laparoscopic cystectomy (RALC) with extracorporeal urinary diversion. To point out that morbidity and mortality of radical cystectomy have improved markedly over the last decades and RALC is an emerging technique showing further advances in postoperative recovery, thus demanding for more rapid nutrition and mobilisation schemes. PATIENTS AND METHODS: A non-randomised cohort study of 63 patients who underwent RALC at one institution between January 2007 and March 2010. In all, 31 patients underwent RALC without FT and 31 RALC with FT. One patient required conversion to open surgery and was therefore excluded from the study. The FT regimen included early nutrition and the quickest possible mobilisation, while mechanical bowel preparation before surgery, as well as preoperative fasting and nasogastric or abdominal drains after surgery, were omitted. Demographics, perioperative and complication data (according to modified Clavien system), as well as required opioid pain medication were documented prospectively and compared between RALC patients with and without FT. RESULTS: Groups were comparable for demographics, risk factors and clinical stage as well as operative parameters, e.g. mean operating room time, estimated blood loss, lymph nodes removed and postoperative haemoglobin level. In the FT group, abdominal drains were mostly omitted and nasogastric tubes were removed immediately after surgery. There were significant differences in the mobilisation within the room (17.5 vs 31.2 h), the time to a regular diet (4.0 vs 6.6 days) and a remarkably lower use of postoperative morphine equivalents (57.3 vs 92.4 mg) for patients receiving FT. There were no significant differences in the overall complication rates or major complications based on Clavien classification. The informative value of the study is limited by its single-centre, non-randomised design, a relatively small sample size and a possible learning curve bias. CONCLUSIONS: Combining RALC with FT is feasible in the perioperative treatment of these patients. Multifactorial postoperative regimens seem to quicken postoperative recovery of RALC patients without increasing their risk of postoperative complications.

Novel options for the treatment of castration-resistant prostate cancer.

Docetaxel had been the only treatment of castration-resistant prostate cancer (CRPC) that demonstrated a survival benefit for the patients. After its approval, no considerable progress has been made for several years until cabazitaxel and abiraterone acetate demonstrated a significant survival benefit in phase III clinical trials. Apart from that several other new drugs appeared including inhibitors of the androgen receptor (MDV3100), endothelin receptor antagonists (atrasentan, zibotentan), bone-targeted drugs (denosumab, Alpharadin) and immunotherapies (sipuleucel-T) capable of improving the prognosis of patients with CRPC. Here, we review the most recent advances in the treatment of CRPC and highlight the most promising new agents currently being investigated in clinical trials.

[Do's and Dont's for radical cystectomy and urinary diversion - how to minimise postoperative complications]. / "Do's and Dont's" bei der radikalen Zystektomie und Harnableitung: Minimierung von postoperativen Komplikationen.

Radical cystectomy (RC) with urinary diversion is a challenging surgical intervention. There is significant risk of postoperative complications, particularly linked to urinary diversion and the patient's comorbidities. The surgeon and the multidisciplinary team need to be familiar with all potential complications. In order to achieve optimal oncological and functional outcomes, multiple factors have to be considered during perioperative management, including the adherence to evidence-based guidelines, standardised concepts of enhanced recovery and best surgical practice for RC and urinary diversion. All measures should aim to minimise complication rates after RC and to accelerate recovery. We summarise essential Dos and Don'ts when performing RC with different forms of urinary diversion.