European Association of Urology Guidelines on Primary Urethral Carcinoma-2020 Update.

CONTEXT: Primary urethral carcinoma (PUC) is a rare cancer accounting for <1% of all genitourinary malignancies. OBJECTIVE: To provide updated practical recommendations for the diagnosis and management of PUC. EVIDENCE ACQUISITION: A systematic search interrogating Ovid (Medline), EMBASE, and the Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews was performed. EVIDENCE SYNTHESIS: Urothelial carcinoma of the urethra is the predominant histological type of PUC (54-65%), followed by squamous cell carcinoma (16-22%) and adenocarcinoma (10-16%). Diagnosis of PUC depends on urethrocystoscopy with biopsy and urinary cytology. Pathological staging and grading are based on the tumour, node, metastasis (TNM) classification and the 2016 World Health Organization grading systems. Local tumour extent and regional lymph nodes are assessed by magnetic resonance imaging, and the presence of distant metastases is assessed by computed tomography of the thorax/abdomen and pelvis. For all patients with localised distal tumours (≤T2N0M0), partial urethrectomy or urethra-sparing surgery is a valid treatment option, provided that negative intraoperative surgical margins can be achieved. Prostatic Ta-Tis-T1 PUC can be treated with repeat transurethral resection of the prostate and bacillus Calmette-Guérin. In prostatic or proximal ≥ T2N0 disease, neoadjuvant cisplatin-based chemotherapy should be considered prior to radical surgery. All patients with locally advanced disease (≥T3N0-2M0) should be discussed within a multidisciplinary team. In men with locally advanced squamous cell carcinoma, curative radiotherapy combined with radiosensitising chemotherapy can be offered for definitive treatment and genital preservation. In patients with local urethral recurrence, salvage surgery or radiotherapy can be offered. For patients with distant metastatic disease, systemic therapy based on tumour characteristics can be evaluated. CONCLUSIONS: These updated European Association of Urology guidelines provide up-to-date guidance for the contemporary diagnosis and management of patients with suspected PUC. PATIENT SUMMARY: Primary urethral carcinoma (PUC) is a very rare, but aggressive disease. These updated European Association of Urology guidelines provide evidence-based guidance for clinicians treating patients with PUC.

Complication rate after cystectomy following pelvic radiotherapy: an international, multicenter, retrospective series of 682 cases.

PURPOSE: Conflicting evidence exists on the complication rates after cystectomy following previous radiation (pRTC) with only a few available series. We aim to assess the complication rate of pRTC for abdominal-pelvic malignancies. METHODS: Patients treated with radical cystectomy following any previous history of RT and with available information on complications for a minimum of 1 year were included. Univariable and multivariable logistic regression models were used to assess the relationship between the variable parameters and the risk of any complication. RESULTS: 682 patients underwent pRTC after a previous RT (80.5% EBRT) for prostate, bladder (BC), gynecological or other cancers in 49.1%, 27.4%, 9.8% and 12.9%, respectively. Overall, 512 (75.1%) had at least one post-surgical complication, classified as Clavien ≥ 3 in 29.6% and Clavien V in 2.9%. At least one surgical complication occurred in 350 (51.3%), including bowel leakage in 6.2% and ureteric stricture in 9.4%. A medical complication was observed in 359 (52.6%) patients, with UTI/pyelonephritis being the most common (19%), followed by renal failure (12%). The majority of patients (86%) received an incontinent urinary diversion. In multivariable analysis adjusted for age, gender and type of RT, patients treated with RT for bladder cancer had a 1.7 times increased relative risk of experiencing any complication after RC compared to those with RT for prostate cancer (p = 0.023). The type of diversion (continent vs non-continent) did not influence the risk of complications. CONCLUSION: pRTC carries a high rate of major complications that dramatically exceeds the rates reported in RT-naïve RCs.

The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin.

OBJECTIVES: To determine if a re-transurethral resection (TUR), in the presence or absence of muscle at the first TUR in patients with T1-high grade (HG)/Grade 3 (G3) bladder cancer, makes a difference in recurrence, progression, cancer specific (CSS) and overall survival (OS). PATIENTS AND METHODS: In a large retrospective multicentre cohort of 2451 patients with T1-HG/G3 initially treated with bacille Calmette-Guérin, 935 (38%) had a re-TUR. According to the presence or absence of muscle in the specimen of the primary TUR, patients were divided in four groups: group 1 (no muscle, no re-TUR), group 2 (no muscle, re-TUR), group 3 (muscle, no re-TUR) and group 4 (muscle, re-TUR). Clinical outcomes were compared across the four groups. RESULTS: Re-TUR had a positive impact on recurrence, progression, CSS and OS only if muscle was not present in the primary TUR specimen. Adjusting for the most important prognostic factors, re-TUR in the absence of muscle had a borderline significant effect on time to recurrence [hazard ratio (HR) 0.67, P = 0.08], progression (HR 0.46, P = 0.06), CSS (HR 0.31, P = 0.07) and OS (HR 0.48, P = 0.05). Re-TUR in the presence of muscle in the primary TUR specimen did not improve the outcome for any of the endpoints. CONCLUSIONS: Our retrospective analysis suggests that re-TUR may not be necessary in patients with T1-HG/G3, if muscle is present in the specimen of the primary TUR.

The effect of the time interval between diagnosis of muscle-invasive bladder cancer and radical cystectomy on staging and survival: A Netherlands Cancer Registry analysis.

INTRODUCTION: Data from single-center series suggest that a delay in time to radical cystectomy (RC) more than 3 months after diagnosis of muscle-invasive bladder cancer (MIBC) is associated with pathological upstaging and decreased survival. However, limited data is available from population-based studies. In this study, the effect of delayed RC was assessed in a nationwide cohort. MATERIALS AND METHODS: Patients who underwent RC between 2006 and 2010 with primary clinical T2-T4N0M0 urothelial bladder cancer were selected using the Netherlands Cancer Registry database. Data from the Netherlands Cancer Registry was supplemented with data from the Nationwide Network and Registry of Histo- and Cytopathology database in case of incomplete information. The cohort was divided in patients who underwent RC ≤3 months (group I) vs. patients who underwent RC >3 months (group II). Median time from MIBC diagnosis to RC, variables associated with delayed RC >3 and the effect of delayed RC on staging and overall survival (OS) were evaluated in patients who underwent neoadjuvant therapy and patients who did not. RESULTS: A total of 1,782 patients were included. Median follow-up time was 5.1 years for living patients and 1.3 years for deceased patients. Median time from MIBC diagnosis to RC was 50 days (interquartile range: 27 days) and 93% of patients underwent RC≤3 months. Patients older than 75 years (odds ratio [OR] = 0.50; 95% CI: 0.32-0.77), referred for RC (OR = 0.41; 95% CI: 0.26-0.69), and treated in a university hospital (OR = 0.34; 95% CI: 0.21-0.56) were less likely to undergo RC≤3 months. Pathologic upstaging rate (43.9% vs. 42.1%) and node-positive disease rate (20.2% vs. 21.7%) did not differ for group I and II. Delayed RC>3 months was not associated with decreased OS adjusting for confounding variables (hazard ratio = 1.16; 95% CI: 0.91-1.48; P = 0.25). Median time from MIBC diagnosis to RC in patients that received neoadjuvant therapy (n = 105) was 133 days (interquartile range: 62 days). Adjusting for confounding variables, delayed RC>3 months was not associated with OS (hazard ratio = 0.90; 95% CI: 0.45-1.82). CONCLUSIONS: The vast majority of patient underwent RC within 3 months after diagnosis of MIBC, as recommended in the European Association of Urology MIBC guideline. Delayed RC for more than 3 months had no adverse effect on staging and survival.

Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guérin: results of a retrospective multicenter study of 2451 patients.

BACKGROUND: The impact of prognostic factors in T1G3 non-muscle-invasive bladder cancer (BCa) patients is critical for proper treatment decision making. OBJECTIVE: To assess prognostic factors in patients who received bacillus Calmette-Guérin (BCG) as initial intravesical treatment of T1G3 tumors and to identify a subgroup of high-risk patients who should be considered for more aggressive treatment. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data were collected for 2451 T1G3 patients from 23 centers who received BCG between 1990 and 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Using Cox multivariable regression, the prognostic importance of several clinical variables was assessed for time to recurrence, progression, BCa-specific survival, and overall survival (OS). RESULTS AND LIMITATIONS: With a median follow-up of 5.2 yr, 465 patients (19%) progressed, 509 (21%) underwent cystectomy, and 221 (9%) died because of BCa. In multivariable analyses, the most important prognostic factors for progression were age, tumor size, and concomitant carcinoma in situ (CIS); the most important prognostic factors for BCa-specific survival and OS were age and tumor size. Patients were divided into four risk groups for progression according to the number of adverse factors among age ≥ 70 yr, size ≥ 3 cm, and presence of CIS. Progression rates at 10 yr ranged from 17% to 52%. BCa-specific death rates at 10 yr were 32% in patients ≥ 70 yr with tumor size ≥ 3 cm and 13% otherwise. CONCLUSIONS: T1G3 patients ≥ 70 yr with tumors ≥ 3 cm and concomitant CIS should be treated more aggressively because of the high risk of progression. PATIENT SUMMARY: Although the majority of T1G3 patients can be safely treated with intravesical bacillus Calmette-Guérin, there is a subgroup of T1G3 patients with age ≥ 70 yr, tumor size ≥ 3 cm, and concomitant CIS who have a high risk of progression and thus require aggressive treatment.

Lymphotropic nanoparticle-enhanced MRI in prostate cancer: value and therapeutic potential.

Nodal staging in prostate cancer is suboptimal both with respect to current imaging modalities and pelvic lymph node dissection, and thus other techniques are being explored. Lymphotropic nanoparticle-enhanced MRI, also called magnetic resonance lymphography (MRL), is a technique that has shown high sensitivity (65-92 %) and excellent specificity (93-98 %) in detecting prostate cancer lymph node metastases. This technique aids in the detection of metastases in non-enlarged small nodes. MRL has been useful in determining the location and pathways of spread in nodal chains. Knowledge of the location of lymph node involvement is important for decisions regarding appropriate therapeutic options, such as image-guided therapy.. A geographic miss in radiotherapy can be avoided with the use of MRL-guided focal therapy. This paper provides an overview of current literature, lessons learned, and new therapeutic options with nanoparticle-enhanced MRI.

Value of PET/CT and MR lymphography in treatment of prostate cancer patients with lymph node metastases.

PURPOSE: To determine the clinical value of two novel molecular imaging techniques: (11)C-choline positron emission tomography (PET)/computed tomography (CT) and ferumoxtran-10 enhanced magnetic resonance imaging (magnetic resonance lymphography [MRL]) for lymph node (LN) treatment in prostate cancer (PCa) patients. Therefore, we evaluated the ability of PET/CT and MRL to assess the number, size, and location of LN metastases in patients with primary or recurrent PCa. METHODS AND MATERIALS: A total of 29 patients underwent MRL and PET/CT for LN evaluation. The MRL and PET/CT data were analyzed independently. The number, size, and location of the LN metastases were determined. The location was described as within or outside the standard clinical target volume for elective pelvic irradiation as defined by the Radiation Therapy Oncology Group. Subsequently, the results from MRL and PET/CT were compared. RESULTS: Of the 738 LNs visible on MRL, 151 were positive in 23 of 29 patients. Of the 132 LNs visible on PET/CT, 34 were positive in 13 of 29 patients. MRL detected significantly more positive LNs (p < 0.001) in more patients than PET/CT (p = 0.002). The mean diameter of the detected suspicious LNs on MRL was significantly smaller than those detected by PET/CT, 4.9 mm and 8.4 mm, respectively (p < 0.0001). In 14 (61%) of 23 patients, suspicious LNs were found outside the clinical target volume with MRL and in 4 (31%) of 13 patients with PET/CT. CONCLUSION: In patients with PCa, both molecular imaging techniques, MRL and (11)C-choline PET/CT, can detect LNs suspicious for metastasis, irrespective of the existing size and shape criteria for CT and conventional magnetic resonance imaging. On MRL and PET/CT, 61% and 31% of the suspicious LNs were located outside the conventional clinical target volume. Therefore, these techniques could help to individualize treatment selection and enable image-guided radiotherapy for patients with PCa LN metastases.

Randomized phase III study comparing paclitaxel-bleomycin, etoposide, and cisplatin (BEP) to standard BEP in intermediate-prognosis germ-cell cancer: intergroup study EORTC 30983.

PURPOSE: To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC). PATIENTS AND METHODS: Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m(2) in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual. RESULTS: Accrual was from November 1998 to April 2009. A total of 169 patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different. CONCLUSION: T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible patients demonstrated a 12% superior 3-year PFS with T-BEP, which was statistically significant.