LDR-Brachytherapy monotherapy appears unsuited for NCCN unfavorable intermediate-risk prostate cancer patients.

BACKGROUND: To validate the subdivision of intermediate-risk (IR) prostate cancer (PCa) into favorable intermediate-risk (FIR) and unfavorable intermediate-risk (UIR) PCa in a historical patient cohort and to compare 2 different radiotherapy regimens. METHODS: Patients with intermediate-risk (IR) PCa, treated either by 125J-LDR-brachytherapy monotherapy (BT) or by combined-modality radiation therapy (CRT), were retrospectively subclassified into FIR and UIR and reanalyzed with regard to biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), and prostate cancer-specific survival (CSS). Kaplan-Meier product-limit method and log-rank tests were applied to estimate survival probabilities and compare survival, respectively. Uni- and multivariable analyses were performed using Cox proportional hazard regression. RESULTS: Of 490 IR patients, 252 had received BT (86.5% FIR, 13.5% UIR), and 238 had received CRT (30% FIR, 70% UIR). Retrospective analysis revealed that BRFS at 10 years was 81% for BT, and 94% for CRT in FIR patients. For UIR patients, BRFS at 10 years was 37% for BT, and 89% for CRT. MFS at 10 years for FIR patients was 87% for BT, and 94% for CRT. For UIR patients MFS at 10 years was 78% for BT, and 95% for CRT. In multivariable analysis treatment (BT vs. CRT) was the single associated factor for biochemical recurrence, and for metastases in the UIR group (BFRS, P < 0.001, HR 16.07 (CI 4.23-61.10); MFS, P = 0.011, HR 8.43 (CI 1.62-43.9). CONCLUSIONS: Subclassification of IR prostate cancer into FIR and UIR subcategories appears mandatory. For FIR patients, outcomes after BT monotherapy were acceptable. However, clinical failure after 125J-LDR-BT in UIR patients was notably increased, suggesting that BT monotherapy was less successful in this risk group. In contrast, the outcome in UIR patients after CRT was excellent.

Definitions of "Cure" After Low-Dose-Rate Brachytherapy in Low- and Intermediate-Risk Prostate Cancer: Phoenix or Surgical?

Purpose: The aim of this study was to compare a surgical with a Phoenix-derived definition of cure at 4 years after treatment by 125J low-dose-rate brachytherapy (LDR-BT) in patients with low- and intermediate-risk prostate cancer. Methods and Materials: A total of 427 evaluable men with low-risk (62.8%) and intermediate-risk (37.2%) prostate cancer were treated with LDR-BT (160 Gy). Cure was defined at 4 years either as not having experienced a biochemical recurrence by the Phoenix definition, or by a surgical definition, using a posttreatment prostate-specific antigen of ≤0.2 ng/mL. Biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), and cancer-specific survival were calculated at 5 and 10 years using the Kaplan-Meier method. Standard diagnostic test evaluations were used to compare both definitions with regard to later metastatic failure or cancer-specific death. Results: At 48 months, 427 patients were evaluable with a Phoenix-defined and 327 with a surgical-defined cure. At 5 and 10 years BRFS was 97.4% and 89% and MFS was 99.5% and 96.3% in the Phoenix-defined cure cohort, and BRFS was 98.2% and 92.7% and MFS was 100% and 99.4% in the surgical-defined cure cohort. Specificity for cure was 100% for both definitions. Sensitivity was 97.4% for the Phoenix and 96.3% for the surgical definition. The positive predictive value was 100% for both, whereas the negative predictive value was 29% for the Phoenix and 7.7% for the surgical definition. Accuracies of a correct prediction of cure were 94.8% and 96.3% for the Phoenix and the surgical definition, respectively. Conclusions: Both definitions are useful for a reliable assessment of cure after LDR-BT in patients with low-risk and intermediate-risk prostate cancer. Cured patients might follow a less stringent follow-up schedule from 4 years onward, whereas patients not achieving cure at 4 years should be monitored for an extended time.

Re: Results of a randomized trial of treatment modalities in patients with low or early­intermediate risk prostate cancer (PREFERE trial).

The authors of this "Letter to the Editors" express their major concern about selective and biased reporting in this paper.

Risk-adapted management of low-grade bladder tumours: recommendations from the International Bladder Cancer Group (IBCG).

OBJECTIVE: To provide a contemporary update and recommendations for the diagnosis and management of low-grade non-muscle-invasive bladder cancer (BCa) based on current literature and expert consensus of the International Bladder Cancer Group. METHODS: We reviewed published trials, guidelines, meta-analyses and reviews (up to March 2019) and provide recommendations on baseline evaluations, treatment, endpoints, study design and surveillance protocols. RESULTS: Low-grade Ta BCa poses minimal risk to patients in terms of progression and disease-specific survival. Thus, to minimize patient morbidity, this entity should be managed appropriately. After initial diagnosis of low-grade Ta tumour, subsequent stable, low-grade-appearing recurrences can be managed conservatively with office cystoscopy and fulguration or even followed using an active surveillance protocol. Intravesical therapy other than single-dose peri-operative chemotherapy instillation should be used judiciously, and only after assigning appropriate risk points. Routine use of urinary cytology - other than at initial risk stratification, or for patients on active surveillance without therapy - is not recommended; and surveillance cystoscopy may be discontinued after 5 years. Clinical studies in this group of patients should focus on recurrence rates, and time to recurrence, rather than progression events. CONCLUSIONS: The International Bladder Cancer Group has developed formal recommendations regarding the diagnosis, treatment and surveillance of low-grade non-muscle-invasive BCa to minimize morbidity and encourage uniformity among studies in this disease.

Comparison of outcome endpoints in intermediate- and high-risk prostate cancer after combined-modality radiotherapy.

PURPOSE: To compare a standard radio-oncological and a surgical biochemical failure definition after combined-modality radiation therapy (CRT) in men with intermediate- and high-risk prostate cancer. METHODS: 425 men were treated with external beam radiotherapy (59.4 Gy, 33 fractions) and 125J seed-brachytherapy (S-BT, 100 Gy). Biochemical recurrence (BR) was defined either as radio-oncologic (rBR), using a +2 ng/mL prostate-specific antigen (PSA) increase above a nadir value, or as surgical (sBR), using a 2-year posttreatment PSA of ≥0.2 ng/mL. Biochemical recurrence-free, metastasis-free, cancer-specific, and overall survival were calculated at 5 and 10 years using the Kaplan-Meier method. Standard validation tests were used to compare both thresholds. RESULTS: After a median of 7 years, overall recurrence rates were 10.4% and 31.5% for rBR and sBR definitions, respectively. Both failure definitions proved sensitive for the prediction of metastases and cancer-specific death, whereas the rBR definition was significantly more specific. The accuracies of a correct prediction of metastases and death of prostate cancer were 73.1% vs. 96.2% and 72.2% vs. 92.9% for sBR vs. rBR, respectively. The inferior validity results of the sBR definition were attributable to a PSA-bounce phenomenon occurring in 56% of patients with sBR. Still, using the less suitable sBR definition, the results of CRT compared favorably to BRFS rates of surgical interventions. CONCLUSION: After CRT, the radio-oncological (aka Phoenix) failure definition is more reliable than a fixed surgical endpoint. Exclusively in high-risk patients, sBR offers a direct comparison across surgical and nonsurgical treatment options at 5 and 10 years.

BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG.

Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established and effective intravesical therapies are available for patients whose tumours recur after BCG, representing a clinically important unmet need. Development and discovery of treatment options for BCG-unresponsive NMIBC is a high priority in order to decrease the morbidity, burden of health-care expenditures, and mortality related to bladder cancer. This Review of treatment options after BCG failure focuses on principles of optimal management emerging therapies, thus enabling a synthesis of recommendations for management for such patients.

Transoral vs. extraoral approach in the treatment of condylar neck fractures.

PURPOSE: The aim of this study was to assess a non-endoscopic transoral versus extraoral technique in the open reduction and internal fixation of displaced or dislocated fractures of the condylar neck. MATERIAL AND METHODS: A total of 104 patients, treated from 2007 to 2012 with 114 class II or class IV fractures according to Spiessl and Schroll were included in this study. Facial nerve function, scarring, pain and functional clinical parameters, such as protrusion, mediotrusion and maximum interincisal distance, were judged clinically (at 21 ± 12.1 months); repositioning and reossification were measured upon preoperative, postoperative and follow-up (at 8.8 ± 7 months) radiographs. Patient satisfaction was evaluated using the OHIP-G 14 questionnaire. RESULTS: In all, 36 patients (35%) with 43 fractures (38%) presented for clinical follow-up. Both treatment groups showed clinically and radiologically comparable results. Scarring was obvious in all extraorally treated patients, and hypertrophic scars occurred in four class IV cases (24%). One class IV patient (6%) had a persistent facial nerve palsy; temporary pareses were more frequent (n = 4; 24%). CONCLUSION: The transoral approach did not jeopardize facial nerve function, and extraoral scars were avoided. Repositioning and fixation results and the frequency of revision operations were comparable. The transoral approach can be recommended generally in class II and class IV cases.

Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987.

PURPOSE: The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival. PATIENTS AND METHODS: We conducted a randomized phase III study to compare paclitaxel/cisplatin/gemcitabine (PCG) with GC in patients with locally advanced or metastatic urothelial carcinoma. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate, and toxicity. RESULTS: From 2001 to 2004, 626 patients were randomly assigned; 312 patients were assigned to PCG, and 314 patients were assigned to GC. After a median follow-up of 4.6 years, the median OS was 15.8 months on PCG versus 12.7 months on GC (hazard ratio [HR], 0.85; P = .075). OS in the subgroup of all eligible patients was significantly longer on PCG (3.2 months; HR, 0.82; P = .03), as was the case in patients with bladder primary tumors. PFS was not significantly longer on PCG (HR, 0.87; P = .11). Overall response rate was 55.5% on PCG and 43.6% on GC (P = .0031). Both treatments were well tolerated, with more thrombocytopenia and bleeding on GC than PCG (11.4% v 6.8%, respectively; P = .05) and more febrile neutropenia on PCG than GC (13.2% v 4.3%, respectively; P < .001). CONCLUSION: The addition of paclitaxel to GC provides a higher response rate and a 3.1-month survival benefit that did not reach statistical significance. Novel approaches will be required to obtain major improvements in survival of incurable urothelial cancer.

European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update.

CONTEXT: The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice. OBJECTIVE: This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references. EVIDENCE SYNTHESIS: There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options. CONCLUSIONS: These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient's specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status.

EAU guidelines on the diagnosis and treatment of urothelial carcinoma in situ.

OBJECTIVES: On behalf of the European Association of Urology (EAU), guidelines for the diagnosis, therapy and follow-up of patients with urothelial carcinoma in situ (CIS) have been established. METHOD: The recommendations in these guidelines are based on a recent comprehensive overview and meta-analysis in which two panel members have been involved (RS and AVDM). A systematic literature search was conducted using Medline, the US Physicians' Data Query (PDQ), the Cochrane Central Register of Controlled Trials, and reference lists in trial publications and review articles. RESULTS: Recommendations are provided for the diagnosis, conservative and radical surgical treatment, and follow-up of patients with CIS. Levels of evidence are influenced by the lack of large randomized trials in the treatment of CIS.