S. Horenblas

Laparoscopic Sentinel Lymph Node Biopsy for Prostate Cancer: The Relevance of Locations Outside the Extended Dissection Area

Objective. To assess the relevance of sentinel lymph nodes (SNs) outside the extended pelvic lymph node dissection area (e-PLND). Patients and Methods. Evaluation of our laparoscopic SN procedures for prostate cancer patients of intermediate prognosis. Retrospective data collection on the exact location of the excised SNs and the pathology results were analyzed. Results and Limitations. Of the 121 patients, 49 had positive lymph nodes. 37 patients (31%) had SNs outside the e-PLND template. Five of these nodes were tumor bearing but only twice exclusively so. Of the 14 patients considered for salvage treatment, 6 were node positive. 7 of these 14 patients (50%) had SNs outside the extended dissection area, yet none of these nodes were tumor positive. Limitations are those of a retrospective study. Conclusions. Laparoscopic SN biopsy may show SNs outside the e-PLND template in 31% of the patients. However, nodes that are exclusively positive in one of these areas are rare. For the dichotomy positive or negative nodes, the locations outside the e-PLND area are not often relevant. Nevertheless, when all positive nodes are to be treated by resection or radiotherapy, these locations are relevant. When considering salvage treatment for prostate cancer, the method is feasible.

Risk and prognostic significance of metachronous contralateral testicular germ cell tumours

Background:Testicular germ cell tumour (TGCT) patients are at increased risk of developing a contralateral testicular germ cell tumour (CTGCT). It is unclear whether TGCT treatment affects CTGCT risk.Methods:The risk of developing a metachronous CTGCT (a CTGCT diagnosed ⩾6 months after a primary TGCT) and its impact on patient’s prognosis was assessed in a nationwide cohort comprising 3749 TGCT patients treated in the Netherlands during 1965–1995. Standardised incidence ratios (SIRs), comparing CTGCT incidence with TGCT incidence in the general population, and cumulative CTGCT incidence were estimated and CTGCT risk factors assessed, accounting for competing risks.Results:Median follow-up was 18.5 years. Seventy-seven metachronous CTGCTs were diagnosed. The SIR for metachronous CTGCTs was 17.6 (95% confidence interval (95% CI) 13.9–22.0). Standardised incidence ratios remained elevated for up to 20 years, while the 20-year cumulative incidence was 2.2% (95% CI 1.8–2.8%). Platinum-based chemotherapy was associated with a lower CTGCT risk among non-seminoma patients (hazard ratio 0.37, 95% CI 0.18–0.72). The CTGCT patients had a 2.3-fold (95% CI 1.3–4.1) increased risk to develop a subsequent non-TGCT cancer and, consequently, a 1.8-fold (95% CI 1.1–2.9) higher risk of death than patients without a CTGCT.Conclusion:The TGCT patients remain at increased risk of a CTGCT for up to 20 years. Treatment with platinum-based chemotherapy reduces this risk.

Serum Hemoglobin Levels Predict Response to Strontium-89 and Rhenium-186-HEDP Radionuclide Treatment for Painful Osseous Metastases in Prostate Cancer

Objective: Retrospective comparative analysis of strontium-89 chloride (Sr89) and rhenium-186-hydroxyethylidene diphosphonate (Re186-HEDP) radionuclide treatment to find predictors of response in patients with painful metastases from hormone refractory prostate cancer. Patients and Methods: Clinical data from 60 hormone refractory PCA patients (i.e. rising PSA at castrate testosterone serum levels) was obtained. Twenty-nine were treated with Sr89, 31 were treated with Re186-HEDP for painful osseous metastasis. Response was defined as a patient-reported decrease in pain and/or reduction in pain medication with stable pain level. Hematological parameters and serum levels of PSA, alkaline phosphatase, and lactate dehydrogenase were assessed prior to and at 4-week intervals after treatment. Results: Median survival of all patients was 7 months (95% CI: 6–9 months). Overall, 33/60 (55%) patients reported a decrease in pain after the first radionuclide treatment. This percentage was similar for patients treated with Re168-HEDP and Sr89. Mean duration of reported pain response was 75 days (± 68 days) for Sr89 and 61 days (± 56 days) for Re186-HEDP, which was not significantly different. A lower blood hemoglobin concentration was associated with a lower pain response rate. In a multivariate Cox regression analysis, pain response to radionuclide treatment predicted longer survival after treatment. Conclusions: Pain response was present in 55% of patients. Serum hemoglobin concentration prior to radionuclide treatment predicted pain response for both Re186-HEDP and Sr89. A reduction in pain upon radionuclide treatment was associated with a longer survival after treatment.

Short-Term Outcome after Cystectomy: Comparison of Two Different Perioperative Protocols

Aim: To compare the outcome of two perioperative protocols with respect to postoperative management of cystectomy patients. Patients and Methods: Between June 2007 and November 2008, 85 consecutive patients with bladder cancer were treated with cystectomy and urinary diversion. Patients were operated in two hospitals by four urologic surgeons. In protocol A, patients were enterally fed via a postpyloric tube while the nasogastric tube (NGT) was removed directly after cystectomy and selective decontamination of the digestive tract was given until normal oral intake. In protocol B, postcystectomy management consisted of total parenteral nutrition by a central venous line and NGT removal after 24 h. Hospital stay and complications were compared between the two hospitals. Results: More than half of all patients (52%) developed one or more complications within 30 days after surgery, 37% in protocol A and 71% in protocol B (p = 0.002). Higher ASA score and protocol type were the only factors significantly associated with early complications in both uni- and multivariate analyses. Length of stay was significantly shorter with protocol A as compared to protocol B, 13 days versus 19 days (p = 0.006). Conclusions: Cystectomy and urinary diversion is a procedure with considerable risk of complications. Enteral nutrition might be advantageous as compared to parenteral nutrition, showing fewer complications and shorter hospital stay. A high ASA score is associated with more early complications. Selective bowel decontamination may have an additional role in preventing infectious complications after cystectomy.

Extended Continuous Oral Temozolomide in Patients with Progressive Metastatic Renal Cell Carcinoma Not Responding to Interferon Alpha 2b

Abstract The aim of the study was to evaluate the toxicity and efficacy of oral extended continuous temozolomide in patients with progressive metastatic renal cell carcinoma (RCC) not responding to immunotherapy after removal of the primary tumor. Patients with progressive metastatic RCC received protracted temozolomide 100 mg/m2 orally on days 1-21 every 28 days. Response was assessed after 2 cycles to be followed by another 2 cycles in the absence of progression. After 4 cycles only patients with further remission and acceptable toxicity were to continue. No objective responses were observed in 12 patients and the trial was stopped prematurely in stage 1. Six patients remained stable during 4 cycles of temozolomide (4 months), only one of these remained stable for another 2 months after having stopped treatment. Five patients progressed after the initial 2 cycles and one after the first cycle. Overall survival was 15.5 months (range 1-36 months). Repeated cycles of 3 weeks oral temozolomide 100 mg/m2 followed by one week rest proved tolerable though this regimen may only have limited activity against metastatic RCC.

Shared Decision Making in Prostate Cancer Care—Encouraging Every Patient to be Actively Involved in Decision Making or Ensuring the Patient Preferred Level of Involvement?

Purpose: The aims of this study were to 1) describe preferred and experienced roles in treatment decision making among patients with localized prostate cancer, 2) identify how often the roles experienced by patients matched their preferred roles and 3) determine whether active involvement in decision making regardless of role preferences or concordance between preferred and experienced roles would be the strongest predictor of more favorable patient reported outcomes. Materials and Methods: In this prospective, multicenter, observational study we obtained serial questionnaire data from 454 patients with newly diagnosed, localized prostate cancer (cT1‐cT2, or Gleason 7 or less and prostate specific antigen 20 ng/ml or less). Questionnaires were completed prior to treatment and at the 3, 6 and 12‐month posttreatment followups. Clinical data were obtained from the patient medical records. Active involvement and role concordance were operationalized using the CPS (Control Preferences Scale). ANOVA and effect sizes (small and medium Cohen d = 0.2 and 0.5, respectively) were used to compare patient knowledge of prostate cancer, decision conflict, decision regret and overall health related quality of life. Results: Of the patients 393 (87%) reported having been actively involved in treatment decision making. However, 78 patients (17%) indicated having had less or more involvement than preferred. Active involvement was significantly associated with more prostate cancer knowledge (d = 0.30), less decision conflict (d = 0.52) and less decision regret (d = 0.34). Role concordance was also but less strongly associated with less decision conflict (d = 0.41). Conclusions: Our findings support a policy of encouraging all patients with localized prostate cancer regardless of their stated role preferences to be actively involved in the treatment decision.

The accuracy of patients’ perceptions of the risks associated with localised prostate cancer treatments

To assess the accuracy of patients’ perceptions of the risks associated with localised prostate cancer treatments (radical prostatectomy [RP], radiotherapy [RT], and active surveillance [AS]), and to identify correlates of misperceptions.

735 Nomogram predicting cancer specific mortality (CSM) after neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer (BC): Results of an international consortium

INTRODUCTION AND OBJECTIVES: Long non-coding RNAs (lncRNAs) are emerging as important drivers of disease progression, and have been shown to modulate gene expression at several levels. Unfortunately, the molecular functions of a majority of lncRNAs identified are still poorly understood. While recent studies have identified subtypes of muscle-invasive bladder cancer (MIBC) at the mRNA level, the overall goal of this study is to obtain a deeper understanding of the lncRNAs that contribute to the molecular mechanisms that underlie the intrinsic subtypes of MIBC. METHODS: In this study, we utilized TCGA’s RNA-sequencing data to extract whole genome lncRNA expression from 211 MIBCs. Unsupervised consensus clustering was utilized to identify subtypes based on lncRNA expression profiles, and differential expression analysis was performed in the R statistical programming environment. To further study the lncRNAs associated with the luminal subtype, cell lines were exposed to rosiglitazone, a PPARg agonist, and RNA-sequencing was performed. PPARg associated lncRNA candidates were validated in an independent cohort using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Consensus clustering of lncRNA expression identified two intrinsic subtypes of MIBCs, which were synonymous with the intrinsic basal and luminal subtypes recently discovered through mRNA expression profiling. Previous work has shown that PPARg is amplified in approximately 15% of luminal MIBCs, and luminal MIBCs are enriched with an activePPARgmRNAexpression signature. In this study, lncRNAs up-regulated after exposure to rosiglitazone were highly expressed in luminal MIBCs, as confirmed by gene set enrichment analysis (GSEA). Differential expression analysis revealed SNHG18 to be up-regulated after PPARg activation, and to be highly expressed in luminal MIBCs. RNA immunoprecipitation studies confirmed that SNHG18 is directly bound by PPARg, and subsequent knockdown of SNHG18 resulted in decreased expression of several luminal PPARg target genes including uroplakins and fibroblast growth factor receptor-3 (FGFR3). CONCLUSIONS: Currently, FGFR3 is an important therapeutic target in MIBCs with activating mutations occurring in approximately 17% of cases. Overall, we have identified a novel lncRNA, SNHG18, to be a co-activator of PPARg that controls downstream expression of FGFR3. The results suggest that SNHG18 could potentially serve as a predictive biomarker, or as a possible drug target to increase the efficiency of FGFR3 targeted therapies.

22 Neoadjuvante dose-dense MVAC voor spierinvasief blaascarcinoom

SamenvattingNeoadjuvante cisplatinehoudende chemotherapie voor spierinvasief blaascarcinoom resulteert bij 30- 40% van de patiënten tot complete pathologische respons (CPR) en een betere overleving dan cystectomie alleen.

221 Prostate sparing cystectomy: 20 years single center experience

INTRODUCTION AND OBJECTIVES: Patients who experience disease recurrence after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) have a very poor prognosis. Most recurrences occur during the first two years following RC. The incidence, patterns, and prognosis of late recurrences (LRs) following RC have not been well described. METHODS: We queried our prospectively maintained institutional database and identified 1953 consecutive patients who underwent RC for UCB from 1995-2010. We identified patients who experienced disease recurrence following RC and analyzed both nonurothelial tract disease recurrence and urothelial recurrence. Late recurrence was defined as a non-urothelial tract recurrence occurring three or more years following RC. RESULTS: Of 648 UCB patients who experienced non-urothelial tract disease recurrence following RC, 93 (14%) occurred greater than 3 years following RC, and 42 (6%) occurred after 5 years (range 3.01 e 12.89 years). Of these 93 LRs, 22 (24%) were local, 54 (58%) were distant, and 17 (18%) were both local and distant. Sites of metastasis in patients with LRs included 21 (23%) lung, 20 (22%) bone, 47 (51%) lymphatic, 18 (19%) liver, 20 (22%) pelvis, and 5 (5%) other. Urothelial tract recurrences were identified in 44 of 93 patients with LR, 30 upper tract and 18 urethral. After excluding 17 patients in whom the LR could be ascribed to an invasive upper tract second primary tumor, 76 LR patients were left for analysis. The stage distribution at RC for LR patients was pT0 (7%), pTa (5%), pTis (18%), pT1 (12%), pT2 (26%), pT3 (21%), and pT4 (8%). Twelve LR patients (16%) had LN-positive disease. Eleven LR patients had received pre-operative cisplatin-based chemotherapy and 8 received adjuvant chemotherapy. LR patients were more likely to have organ-confined disease at RC (62% vs. 21%, p<0.001) and concomitant CIS (78% vs. 61%, p1⁄40.02) than patients experiencing recurrence within 3 years. However, the prognosis following recurrence was similarly poor for patients experiencing LR as it was for early recurrence, although LR patients had a slightly longer time from recurrence to death (p1⁄40.002). CONCLUSIONS: Bladder cancer patients treated with RC remain at risk for disease recurrence for many years, although the majority of patients who will recur do so within the first two years. Patients who experience late recurrence have different disease characteristics than those who experience early recurrence. Continued surveillance for detection of local, distant, and urothelial recurrences following RC may be beneficial.