Transcriptomic and clinical heterogeneity of metastatic disease timing within metastatic castration-sensitive prostate cancer.

BACKGROUND: Metastatic castration-sensitive prostate cancer (mCSPC) is commonly classified into high- and low-volume subgroups which have demonstrated differential biology, prognosis, and response to therapy. Timing of metastasis has similarly demonstrated differences in clinical outcomes; however, less is known about any underlying biologic differences between these disease states. Herein, we aim to compare transcriptomic differences between synchronous and metachronous mCSPC and identify any differential responses to therapy. PATIENTS AND METHODS: We performed an international multi-institutional retrospective review of men with mCSPC who completed RNA expression profiling evaluation of their primary tumor. Patients were stratified according to disease timing (synchronous versus metachronous). The primary endpoint was to identify differences in transcriptomic profiles between disease timing. The median transcriptomic scores between groups were compared with the Mann-Whitney U test. Secondary analyses included determining clinical and transcriptomic variables associated with overall survival (OS) from the time of metastasis. Survival analysis was carried out with the Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 252 patients were included with a median follow-up of 39.6 months. Patients with synchronous disease experienced worse 5-year OS (39% versus 79%; P < 0.01) and demonstrated lower median androgen receptor (AR) activity (11.78 versus 12.64; P < 0.01) and hallmark androgen response (HAR; 3.15 versus 3.32; P < 0.01). Multivariable Cox regression identified only high-volume disease [hazard ratio (HR) = 4.97, 95% confidence interval (CI) 2.71-9.10; P < 0.01] and HAR score (HR = 0.51, 95% CI 0.28-0.88; P = 0.02) significantly associated with OS. Finally, patients with synchronous (HR = 0.47, 95% CI 0.30-0.72; P < 0.01) but not metachronous (HR = 1.37, 95% CI 0.50-3.92; P = 0.56) disease were found to have better OS with AR and non-AR combination therapy as compared with monotherapy (P value for interaction = 0.05). CONCLUSIONS: We have demonstrated a potential biologic difference between metastatic timing of mCSPC. Specifically, for patients with low-volume disease, those with metachronous low-volume disease have a more hormone-dependent transcriptional profile and exhibit a better prognosis than synchronous low-volume disease.

Surgical management of acquired rectourethral fistula: a retrospective analysis of 52 consecutive patients.

BACKGROUND: Acquired rectourethral fistula (RUF) is an uncommon complication mostly resulting from surgery or radiation. Standardization of the surgical management is lacking. The aim of this study was to report our experience with surgery for RUF. METHODS: This was a retrospective study of a prospectively maintained clinical database. The surgical strategy was tailored to complexity of RUF, presence of sepsis, history of radiation and residual urinary/fecal functionality. Outcomes measured were RUF closure and permanent fecal/urinary diversion. Impact of radiotherapy was also assessed. RESULTS: Between November 2002 and January 2019, 52 patients were identified (100% males). Median follow-up was 10.5 (0.5-16.8) years. Three patients had RUF closure after conservative management. The remaining 49 patients had a total of 76 procedures. The cumulative closure rate after the first, second and third attempt was 55.1%, 85.7% and 95.9%, respectively. Fistula closure together with preservation of the fecal and urinary function was achieved in 49%, 65.3% and 67.3% after the first, second and third repair, respectively. The overall success rate for transanal, transperineal, restorative transabdominal and non-restorative transabdominal procedures was 35.7%, 64.3%, 57.1% and 94.1%, respectively. A significantly higher rate of urinary/intestinal stomas was observed in the irradiated vs non-irradiated patients (84.2% vs 42.4%; p = 0.004). CONCLUSIONS: Surgery ensured healing in 96% of the patients. Radiotherapy led to higher rate of permanent urinary/fecal diversion. Nearly all irradiated patients who had transabdominal repair end up with a definitive stoma. When transperineal repair with gracilis flap interposition was used, the rate of fistula closure approached 90%. A treatment algorithm is proposed.

Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy.

PURPOSE: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG. METHODS: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups. RESULTS: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024) CONCLUSIONS: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.

Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG: not as bad as previously thought.

PURPOSE: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG. METHODS: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model. RESULTS: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P < 0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P < 0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen. CONCLUSIONS: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.

Older patients with low Charlson score and high-risk prostate cancer benefit from radical prostatectomy.

INTRODUCTION: The aim of the study was to identify the appropriate level of Charlson comorbidity index (CCI) in older patients (>70 years) with high-risk prostate cancer (PCa) to achieve survival benefit following radical prostatectomy (RP). METHODS: We retrospectively analyzed 1008 older patients (>70 years) who underwent RP with pelvic lymph node dissection for high-risk prostate cancer (preoperative prostate-specific antigen >20 ng/mL or clinical stage ≥T2c or Gleason ≥8) from 14 tertiary institutions between 1988 and 2014. The study population was further grouped into CCI < 2 and ≥2 for analysis. Survival rate for each group was estimated with Kaplan-Meier method and competitive risk Fine-Gray regression to estimate the best explanatory multivariable model. Area under the curve (AUC) and Akaike information criterion were used to identify ideal 'Cut off' for CCI. RESULTS: The clinical and cancer characteristics were similar between the two groups. Comparison of the survival analysis using the Kaplan-Meier curve between two groups for non-cancer death and survival estimations for 5 and 10 years shows significant worst outcomes for patients with CCI ≥ 2. In multivariate model to decide the appropriate CCI cut-off point, we found CCI 2 has better AUC and p value in log rank test. CONCLUSION: Older patients with fewer comorbidities harboring high-risk PCa appears to benefit from RP. Sicker patients are more likely to die due to non-prostate cancer-related causes and are less likely to benefit from RP.

RANK/OPG ratio of expression in primary clear-cell renal cell carcinoma is associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs.

BACKGROUND: Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs. METHODS: Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT-PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan-Meier estimates and Cox regression. RESULTS: We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29-0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31-0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44-3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28-0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19-0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29-0.73); P=0.001). CONCLUSIONS: RANK/OPG ratio of expression in primary ccRCC is associated with BM and prognosis in patients treated with anti-VEGFR-TKIs. Prospective validation is warranted.

Guidelines for the definition of time-to-event end points in renal cell cancer clinical trials: results of the DATECAN project†.

BACKGROUND: In clinical trials, the use of intermediate time-to-event end points (TEEs) is increasingly common, yet their choice and definitions are not standardized. This limits the usefulness for comparing treatment effects between studies. The aim of the DATECAN Kidney project is to clarify and recommend definitions of TEE in renal cell cancer (RCC) through a formal consensus method for end point definitions. MATERIALS AND METHODS: A formal modified Delphi method was used for establishing consensus. From a 2006-2009 literature review, the Steering Committee (SC) selected 9 TEE and 15 events in the nonmetastatic (NM) and metastatic/advanced (MA) RCC disease settings. Events were scored on the range of 1 (totally disagree to include) to 9 (totally agree to include) in the definition of each end point. Rating Committee (RC) experts were contacted for the scoring rounds. From these results, final recommendations were established for selecting pertinent end points and the associated events. RESULTS: Thirty-four experts scored 121 events for 9 end points. Consensus was reached for 31%, 43% and 85% events during the first, second and third rounds, respectively. The expert recommend the use of three and two endpoints in NM and MA setting, respectively. In the NM setting: disease-free survival (contralateral RCC, appearance of metastases, local or regional recurrence, death from RCC or protocol treatment), metastasis-free survival (appearance of metastases, regional recurrence, death from RCC); and local-regional-free survival (local or regional recurrence, death from RCC). In the MA setting: kidney cancer-specific survival (death from RCC or protocol treatment) and progression-free survival (death from RCC, local, regional, or metastatic progression). CONCLUSIONS: The consensus method revealed that intermediate end points have not been well defined, because all of the selected end points had at least one event definition for which no consensus was obtained. These clarified definitions of TEE should become standard practice in all RCC clinical trials, thus facilitating reporting and increasing precision in between trial comparisons.

Does 11C-choline PET-CT contribute to multiparametric MRI for prostate cancer localisation?

BACKGROUND AND PURPOSE: The aim of this work was to determine whether 11C-choline positron emission tomography (PET)-computed tomography (CT) makes a positive contribution to multiparametric magnetic resonance imaging (MRI) for localisation of intraprostatic tumour nodules. PATIENTS AND METHODS: A total of 73 patients with biopsy-proven intermediate- and high-risk prostate cancer were enrolled in a prospective imaging study consisting of T2-weighted (T2w), dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI and 11C-choline PET-CT before radical prostatectomy. Cancerous regions were delineated on the whole-mount prostatectomy sections and on the different MRI modalities and analysed in 24 segments per patient (3 sections, 8 segments each). To analyse PET-CT images, standardized uptake values (SUV) were calculated per segment. RESULTS: In total, 1,752 segments were analyzed of which 708 (40.4%) were found to be malignant. A high specificity (94.7, 93.6 and 92.2%) but relatively low sensitivity (31.2, 24.9 and 44.1%) for tumour localisation was obtained with T2w, DCE and DW MRI, respectively. Sensitivity values significantly increased when combining all MRI modalities (57.2%). For PET-CT, mean SUVmax of malignant octants was significantly higher than mean SUVmax of benign octants (3.68±1.30 vs. 3.12±1.02, p<0.0001). In terms of accuracy, the benefit of adding PET-CT to (multiparametric) MRI was less than 1%. CONCLUSION: The additional value of 11C-choline PET-CT to MRI in localising intraprostatic tumour nodules is limited, especially when multiparametric MRI is used.

Management of localized and locally advanced renal tumors. A contemporary review of current treatment options.

About 70% of patients with renal cell carcinoma present with localized or locally advanced disease at primary diagnosis. Whereas these patients are potentially curable by surgical treatment alone, a further 20% to 30% of patients are diagnosed with primary metastatic disease. Although over the past years medical treatment for metastatic patients has nearly completely changed from immunotherapy to effective treatment with targeted agents, metastatic disease still represents a disease status which is not curable. Also in patients with metastatic disease, surgical treatment of the primary tumor plays an important role, since local tumor related complications can be avoided or minimized by surgery. Furthermore, also improvement of overall survival has been proven for surgery in metastatic patients when combined with cytokine treatment. Hence, surgical combined with systemic treatment as a multi-modal, adjuvant, and neo-adjuvant treatment is also required in patients with advanced or metastatic disease. A growing number of elderly and comorbid patients are currently diagnosed with small renal masses, which has led to increased attention paid to alternative ablative treatment modalities as well as active surveillance strategies, which are applied in order to avoid unnecessary overtreatment in these patients. Since surgical treatment also might enhance the risk of chronic kidney disease with consecutive cardiac disorders as well as reduced overall survival, ablative techniques and active surveillance are increasingly applied. In this review article we focus on current surgical and none-surgical treatment options for the management of patients with localized, locally advanced, and metastatic renal cell carcinoma.

Case-matched analysis of outcome after open retropubic radical prostatectomy in patients with previous preperitoneal inguinal hernia repair.

BACKGROUND: The impact of preperitoneal mesh repair for inguinal hernia on future pelvic surgery is debatable. This retrospective study investigated the impact of previous preperitoneal inguinal hernia repair (PIHR) on outcome after open retropubic radical prostatectomy (RRP) for prostatic cancer. METHODS: Patients who had open RRP and who had previously undergone PIHR were identified. They were compared with a control group of patients matched for age, body mass index and tumour risk profile who had no history of inguinal hernia repair. Outcome measures included intraoperative data, histopathology and results at follow-up. RESULTS: Sixty patients who had undergone open RRP after a previous PIHR were compared with 60 control patients. Operations lasted longer in the PIHR group (median (interquartile range, i.q.r.) 100 (90-120) versus 90 (85-100) min respectively; P < 0·001) and the operation was assessed as more difficult by the surgeon (P = 0·022). Hospital stay was longer for patients who had undergone PIHR (median (i.q.r.) 7 (6-9) versus 6 (5-7) days; P = 0·012) and urinary catheterization was prolonged (13 (11-14) versus 11 (11-12) days; P = 0·006). Among patients with intermediate- and high-risk disease, fewer lymph nodes were excised in the PIHR group than in the control group (median (i.q.r.) 2 (0-7) versus 8 (5-12) nodes; P < 0·001). CONCLUSION: Open RRP for prostatic cancer was more difficult to perform after previous PIHR, and was associated with a longer hospital stay and less adequate lymphadenectomy for intermediate- and high-risk prostatic cancer.

Benefits of early salvage therapy on oncological outcomes in high-risk prostate cancer with persistent PSA after radical prostatectomy.

BACKGROUND: Patients with prostate-specific antigen (PSA) persistence are at the increased risk of disease progression. The aim of our study was to evaluate the impact of early salvage therapy on oncological outcomes in patients with persistent PSA after radical prostatectomy (RP). METHODS: Within a single tertiary centre database, we identified men with persistent (≥ 0.1 ng/ml) versus undetectable (< 0.1 ng/ml) PSA 4-8 weeks after RP for high-risk prostate cancer (HRPCa). The cumulative incidence function was used to estimate cancer-specific survival (CSS) and clinical progression-free survival (CPFS). The Kaplan-Meier method was used to estimate overall survival (OS). The effects on oncological outcomes of salvage radiotherapy (SRT) ± androgen deprivation therapy (ADT) vs. ADT monotherapy were tested in the subgroup of patients with persistent PSA. RESULTS: Of 414 consecutive patients who underwent RP for HRPC, 125 (30.2%) had persistent PSA. Estimated 10-year CPFS, CSS and OS for men with persistent vs. undetectable PSA were 63.8% vs. 93.5%, 78.5% vs. 98.3% and 54% vs. 83.2% (all p < 0.0001), respectively. In men with persistent PSA, ADT alone was associated with higher risk (hazard ratio (HR) for worse CSS (HR 3.9, p = 0.005) and OS (HR 4.7, p < 0.0001) but not for CP (HR 1.6, p = 0.2) when compared with SRT ± ADT. CONCLUSION: In patients who underwent RP for HRPCa, persistent PSA was associated with poor oncological outcomes. Early SRT ± ADT resulted in significantly improved CSS and OS in men with persistent PSA comparing with early androgen deprivation monotherapy.

Treatment of patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC) in Belgium: a real world data analysis.

INTRODUCTION: Abiraterone acetate + prednisone (AAP) and docetaxel have proven their efficacy in the treatment of patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) in clinical trials. However, real-world data are scarce. The goal of this study is to evaluate real-world data on the efficacy and safety of these therapies in mHSPC patients. PATIENTS AND METHODS: Records of 93 patients from 21 different centres were retrospectively reviewed. Primary and secondary endpoints were radiographic and PSA progression-free survival (RPFS - PSA-PFS) and cancer specific and overall survival (CSS - OS), respectively. Adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Differences in oncological outcome and AEs were evaluated between three treatment groups: ADT only (N=26) - ADT + AAP (N=48) - ADT + docetaxel (N=19). Survival analysis was performed using Kaplan-Meier statistics. RESULTS: Median RPFS was 13 months (95% confidence interval [CI]: 9-17) for ADT only, 21 months (95% CI: 19-23) for ADT + AAP and 12 months (95% CI: 11-14) for ADT + docetaxel (p = 0.004). The 1-year PSA-PFS, CSS and OS were 73.5%, 90.7% and 88.7%, respectively, with no significant differences between the three groups. Adverse events of grade 3 or higher were not observed more frequently. CONCLUSION: Retrospective real-world data show a significantly longer RPFS for mHSPC patients treated with ADT + AAP compared to ADT only or ADT + docetaxel at short-term follow-up. This can aid in counselling of mHSPC patients in daily clinical practice.

Polypoid endometriosis of the bladder during pregnancy mimicking urachal carcinoma.

We report a case of polypoid bladder endometriosis in pregnancy. Diagnostic workup showed a vesicouterine well-vascularized polypoid mass, suspicious for malignancy. During pregnancy, the mass was surgically resected with safe oncological margins. Pathological examination of the resected specimen revealed pseudotumoral polypoid endometriosis of the bladder. We illustrate diagnostic pitfalls in the differentiation between bladder endometriosis during pregnancy and malignancy. As a result of pregnancy-related decidualization of vesical endometriosis, differentiation between this rare occurrence and malignant transformation is challenging.

Radiofrequency ablation for the treatment of small renal masses: safety and oncologic efficacy.

The successful introduction of radio frequency ablation (RFA) into various surgical fields has fueled the interest of the urological community to study its application in small renal masses (SRM). However, some controversies remain regarding its oncologic efficacy. In this paper, we review the complication rates and highlight local ablative success and long-term oncologic outcomes of recent, larger RFA series. Review of the recent literature (Medline from January 2003 through May 2011 with the terms ("radiofrequency ablation" OR "catheter ablation") AND ("renal cell carcinoma" OR "renal tumor" OR "renal mass" OR "renal cancer" OR "kidney cancer"). Twelve RFA studies including a minimum of 35 treated tumors, and representing 717 patients were identified and analyzed for local ablative success rates and complications. Reported complications were classified according to Dindo-Clavien. Another five studies representing 172 patients were identified to assess long-term oncologic outcomes. Final pathology revealed 82.3% biopsy-proven renal cell carcinomas (RCCs) in 8 of the 12 evaluable RFA studies. Local ablative success rates after a first RFA session ranged from 67% to 100%. However, accepting a 8.8% repeat ablation rate, final success rates were 89.7-100%, with 7 of 12 studies showing final ablative success in >95%. These results demonstrate RFA to achieve adequate local tumor control regardless of histology. Risk of complications was 13.2%. Of complications, 10% were minor (grade I or II), while only 3.2% were major complications (grade ≥III). Five papers were identified describing oncological outcome at a minimum follow-up of 53 months (range 53-61.2). Progression-free survival, cancer-specific survival and overall survival ranged from 79.9 to 93.8%, 98 to 100% and 58.3 to 85%, respectively. This literature review confirms that RFA can deliver durable local tumor control and excellent long-term oncological outcomes. However, in order to achieve this, a repeat ablation rate of 8.8% has to be accepted. Complication rates are low, with 10% grade I-II and only 3.2% grade >III. These observations render RFA an attractive alternative to surgery in an elderly or comorbid population.

Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients.

INTRODUCTION AND OBJECTIVES: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. MATERIAL AND METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. RESULTS: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.

Salvage Radiotherapy for Prostate Cancer.

For patients experiencing biochemical recurrence in the absence of distant metastasis, salvage radiotherapy (SRT) with or without androgen deprivation therapy (ADT) is currently the only possible curative treatment option. Prostate-specific antigen (PSA) monitoring and the selected use of SRT has some advantages when compared with adjuvant radiotherapy. The most important one is avoidance of a potential overtreatment of patients who would never have disease progression, even in the presence of high-risk pathological features. The identification of a specific PSA cut-off seems to be incorrect. In patients with more adverse pathological features, early SRT administered at the very first sign of a PSA rise granted better disease control. Dose-intensified SRT is feasible and well tolerated with no significant difference in grade 2 or more acute and late toxicity. At least 66 Gy must be given in the salvage setting. ADT has a radio-sensitising effect on the radiotherapy by inhibiting the repair of DNA double-strand breaks. The use of ADT in the salvage setting results in a better oncological outcome. Hormonal therapy is associated with a decrease in quality of life and side-effects depending on the duration of hormone therapy. The oncological benefit of hormone therapy duration depends on their clinical and pathological characteristics. 68-Ga-prostate-specific membrane antigen positron emission tomography-computed tomography is the gold standard in staging prostate cancer patients with biochemical persistence or recurrence after radical prostatectomy. The implementation of 18F-labelled PSMA tracers can provide a further improvement.

Concordance Between Biopsy and Radical Prostatectomy Gleason Scores: Evaluation of Determinants in a Large-Scale Study of Patients Undergoing RARP in Belgium.

To determine whether Gleason scores were concordant between prostate biopsies (bGS) and the definitive resection specimen (pGS) excised with robot-assisted radical prostatectomy (RARP); to identify clinical and pathological factors that might predict upgrading; and to evaluate how upgrading affected outcome. Between 2009 and 2016, 25 Belgian centers participated in collecting prospective data for patients that underwent RARP. We analyzed the concordance rate between the bGS and the pGS in 8021 patients with kappa statistics, and we compared concordance rates from different centers. We assessed the effect of several clinical and pathological factors on the concordance rate with logistic regression analysis. The concordance rate for the entire population was 62.9%. Upgrading from bGS to pGS occurred in 27.3% of patients. The number of biopsies was significantly associated with concordance. Older age (>60 y), a higher clinical T stage (≥cT2), a higher PSA value at the time of biopsy (>10 ng/ml), and more time between the biopsy and the radical prostatectomy were significantly associated with a higher risk of upgrading. Positive margins and PSA relapse occurred more frequently in upgraded patients. Center size did not significantly affect the concordance rate (p = 0.40).This prospective, nationwide analysis demonstrated a Gleason score concordance rate of 62.9%. Upgrading was most frequently observed in the non-concordant group. We identified clinical and pathological factors associated with (non)-concordance. Upgrading was associated with a worse oncological outcome. Center volume was not associated with pathological accuracy.

Reflux changes in adenoidal hyperplasia: a controlled prospective study to investigate its aetiology.

OBJECTIVES: To compare pepsin, carbonic anhydrase III (CAIII), cyclooxygenase-2 (COX-2) and mucin 5AC (MUC5AC) expression in children with adenoid hypertrophy and normal controls. DESIGN: A non-randomised, controlled prospective study. SETTING: Two paediatric hospitals in Adelaide, South Australia. PARTICIPANTS: Children aged 2-10 years, 21 undergoing adenoidectomy and 12 controls undergoing routine dental surgery. MAIN OUTCOME MEASURES: We measured expression of pepsin, CAIII, COX-2 and MUC5AC levels by real-time RT-PCR, immunohistochemistry, and Western blot to determine any difference between children with hyperplastic adenoids and controls. RESULTS: Pepsin was not detected in any study or control adenoid by immunohistochemistry or Western blot. Real-time RT-PCR analysis showed a statistically significant difference between groups with respect to COX-2 (P = 0.027) and MUC5AC (P = 0.02) but no difference in CAIII expression (P = 0.414). A significant correlation was also found between COX-2 and MUC5AC expression (Kendall Tau = 0.4, P = 0.005). CONCLUSION: Our results suggest that the biochemical changes seen in adenoid hypertrophy are different to those seen in reflux-affected tissues. The decreased COX-2 and MUC5AC expression may be due to squamous metaplasia and other inflammatory changes associated with adenoid hypertrophy. Our findings infer there is little evidence of reflux being a major contributory factor in the pathophysiology of adenoidal hypertrophy.

Evaluating a decision aid for patients with localized prostate cancer in clinical practice.

AIM: The aim of the study was to evaluate the usefulness of a decision aid regarding treatment options for patients with early-stage localized prostate cancer. METHODS: 50 patients with newly diagnosed localized prostate cancer received the decision aid and were interviewed twice: before the decision-making consultation with the physicians and before treatment or, in case of watchful waiting, before the follow-up consultation. The physicians (radiation oncologists and urologists) were interviewed after the consultation. RESULTS: The patients became more active partners in the decision-making process: They were better prepared for the consultation, asked more direct information, and were able to make a more deliberative choice. Generally, the use of the decision aid improved the quality of the consultation and resulted in a treatment decision agreed upon by both parties. Sometimes the consultation turned out to be more time-consuming. The decision aid did not only improve the patient-physician interaction but also helped patients to discuss the disease with their partner and family members. CONCLUSION: The use of the decision aid has a positive impact on the consultation and the decision-making process. The policy of involving patients more actively in the decision process should be further implemented in daily practice.