Focal laser ablation as clinical treatment of prostate cancer: report from a Delphi consensus project.

PURPOSE: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. METHODS: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. RESULTS: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. CONCLUSION: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.

Contemporary management of men with high-risk localized prostate cancer in the United States.

This corrects the article DOI: 10.1038/pcan.2017.5.

Contemporary management of men with high-risk localized prostate cancer in the United States.

BACKGROUND: Surgery and radiation-based therapies are standard management options for men with clinically localized high-risk prostate cancer (PCa). Contemporary patterns of care are unknown. We hypothesize the use of surgery has steadily increased in more recent years. METHODS: Using the National Cancer Data Base for 2004-2013, all men diagnosed with high-risk localized PCa were identified using National Comprehensive Cancer Network criteria. Temporal trends in initial management were assessed. Multivariable logistic regression was used to evaluate demographic and clinical factors associated with undergoing radical prostatectomy (RP). RESULTS: In total, 127 391 men were identified. Use of RP increased from 26% in 2004 to 42% in 2013 (adjusted risk ratio (RR) 1.51, 95% CI 1.42-1.60, P<0.001), while external beam radiation therapy (EBRT) decreased from 49% to 42% (P<0.001). African American men had lower odds of undergoing RP (unadjusted rate of 28%, adjusted RR 0.69, 95% CI 0.66-0.72, <0.001) compared to White men (37%). Age was inversely associated with likelihood of receiving RP. Having private insurance was significantly associated with the increased use of RP (vs Medicare, adjusted odds ratio 1.04, 95% CI 1.01-1.08, P=0.015). Biopsy Gleason scores 8-10 with and without any primary Gleason 5 pattern were associated with decreased odds of RP (vs Gleason score ⩽6, both P<0.001). Academic and comprehensive cancer centers were more likely to perform RP compared to community hospitals (both P<0.001). CONCLUSION: The likelihood of receiving RP for high-risk PCa dramatically increased from 2004 to 2013. By 2013, the use of RP and EBRT were similar. African American men, elderly men and those without private insurance were less likely to receive RP.

Increasing incidence of metastatic prostate cancer in the United States (2004-2013).

BACKGROUND: Changes in prostate cancer screening practices in the United States have led to recent declines in overall incidence, but it is unknown whether relaxed screening has led to changes in the incidence of advanced and metastatic prostate cancer at diagnosis. METHODS: We identified all men diagnosed with prostate cancer in the National Cancer Data Base (2004-2013) at 1089 different health-care facilities in the United States. Joinpoint regressions were used to model annual percentage changes (APCs) in the incidence of prostate cancer based on stage relative to that of 2004. RESULTS: The annual incidence of metastatic prostate cancer increased from 2007 to 2013 (Joinpoint regression: APC: 7.1%, P<0.05) and in 2013 was 72% more than that of 2004. The incidence of low-risk prostate cancer decreased from years 2007 to 2013 (APC: -9.3%, P<0.05) to 37% less than that of 2004. The greatest increase in metastatic prostate cancer was seen in men aged 55-69 years (92% increase from 2004 to 2013). CONCLUSIONS: Beginning in 2007, the incidence of metastatic prostate cancer has increased especially among men in the age group thought most likely to benefit from definitive treatment for prostate cancer. These data highlight the continued need for nationwide refinements in prostate cancer screening and treatment.

Standardization of definitions in focal therapy of prostate cancer: report from a Delphi consensus project.

PURPOSE: To reach standardized terminology in focal therapy (FT) for prostate cancer (PCa). METHODS: A four-stage modified Delphi consensus project was undertaken among a panel of international experts in the field of FT for PCa. Data on terminology in FT was collected from the panel by three rounds of online questionnaires. During a face-to-face meeting on June 21, 2015, attended by 38 experts, all data from the online rounds were reviewed and recommendations for definitions were formulated. RESULTS: Consensus was attained on 23 of 27 topics; Targeted FT was defined as a lesion-based treatment strategy, treating all identified significant cancer foci; FT was generically defined as an anatomy-based (zonal) treatment strategy. Treatment failure due to the ablative energy inadequately destroying treated tissue is defined as ablation failure. In targeting failure the energy is not adequately applied to the tumor spatially and selection failure occurs when a patient was wrongfully selected for FT. No definition of biochemical recurrence can be recommended based on the current data. Important definitions for outcome measures are potency (minimum IIEF-5 score of 21), incontinence (new need for pads or leakage) and deterioration in urinary function (increase in IPSS >5 points). No agreement on the best quality of life tool was established, but UCLA-EPIC and EORTC-QLQ-30 were most commonly supported by the experts. A complete overview of statements is presented in the text. CONCLUSION: Focal therapy is an emerging field of PCa therapeutics. Standardization of definitions helps to create comparable research results and facilitate clear communication in clinical practice.

Population-based analysis of treatment modalities and survival for clinically localized small-cell carcinoma of the prostate.

BACKGROUND: Small-cell carcinoma of the prostate is an aggressive cancer whose rarity has prevented the development of a consensus management approach. The objective of the current study was to determine the treatment patterns and evaluate factors affecting overall survival for patients with localized small-cell carcinoma of the prostate. METHODS: After querying the National Cancer Database, we identified all patients diagnosed with localized small-cell carcinoma of the prostate between 1998 and 2011 (n=287). Using Kaplan-Meier curves and Cox regression analyses, we assessed the effect of treatment and clinical stage on overall survival. RESULTS: Treatments included radiation therapy in 46% (n=131), chemotherapy in 38% (n=107), androgen deprivation therapy (ADT) in 22% (n=63) and radical prostatectomy in 13% (n=38). Median overall survival was 14.8 months. Upon multivariate analysis, local therapy (radical prostatectomy or radiation therapy) was associated with improved survival (hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.14-0.38, P<0.001). Advanced clinical stage predicted worse survival among all men (cT3: HR 2.83, 95% CI 1.27-6.32, P=0.011; cT4: HR 3.26, 95% CI 1.50-7.07, P=0.003) and men who received local therapy (cT3: HR 4.67, 95% CI 1.41-15.44, P=0.012; cT4: HR 4.01, 95% CI 1.14-14.08, P=0.03) but not among men who received no local therapy (cT3: HR 1.64, 95% CI 0.51-5.27, P=0.4; cT4: HR 2.35, 95% CI 0.74-7.48, P=0.15). Age, receipt of chemotherapy and ADT, and clinical stage T2 disease (compared with T1) did not predict survival. CONCLUSION: Men with localized small-cell carcinoma of the prostate have a poor overall survival. Local therapy may represent a suitable and underused modality for select patients.

The use of mannitol in partial and live donor nephrectomy: an international survey.

PURPOSE: Animal studies have shown the potential benefits of mannitol as renoprotective during warm ischemia; it may have antioxidant and anti-inflammatory properties and is sometimes used during partial nephrectomy (PN) and live donor nephrectomy (LDN). Despite this, a prospective study on mannitol has never been performed. The aim of this study is to document patterns of mannitol use during PN and LDN. MATERIALS AND METHODS: A survey on the use of mannitol during PN and LDN was sent to 92 high surgical volume urological centers. Questions included use of mannitol, indications for use, physician responsible for administration, dosage, timing and other renoprotective measures. RESULTS: Mannitol was used in 78 and 64 % of centers performing PN and LDN, respectively. The indication for use was as antioxidant (21 %), as diuretic (5 %) and as a combination of the two (74 %). For PN, the most common dosages were 12.5 g (30 %) and 25 g (49 %). For LDN, the most common doses were 12.5 g (36.3 %) and 25 g (63.7 %). Overall, 83 % of centers utilized mannitol, and two (percent or centers??) utilized furosemide for renoprotection. CONCLUSIONS: A large majority of high-volume centers performing PN and LDN use mannitol for renoprotection. Since there are no data proving its value nor standardized indication and usage, this survey may provide information for a randomized prospective study.

Cause-specific mortality following radical prostatectomy.

BACKGROUND: To evaluate cause-specific mortality following radical prostatectomy (RP) in a population cohort of US men adjusting for competing risks. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to identify 120,392 men undergoing RP for clinically localized prostate cancer between 1988 and 2003. Cause-specific mortality data were extracted through 2006 and cumulative incidence was estimated using a competing risks approach. RESULTS: The stage distribution of the cancers was 32% local, 28% regional, 40% unknown, and 80% of tumors Gleason ≤ 7. Median follow-up was 7 years. The 15-year prostate cancer-specific mortality was 5.3% and the non-prostate cancer mortality was 30.6%. Stage, grade and race had minimal impact on non-prostate cancer mortality. At 15 years following surgery, mortality due to cardiovascular diseases was 11%, other cancers 9.1%, and other causes 10.5%. Among men ≥ 65 years, 15-year cancer-specific mortality was 6% and non-prostate cancer mortality was 40.8%. CONCLUSIONS: Following RP, death from cardiovascular diseases, other cancers, and other causes is far more common than death from prostate cancer. In men diagnosed with prostate cancer, significant efforts should be made to prevent, diagnose, and treat these diseases.

Robotic-assisted partial cystectomy for recurrent extra-adrenal pheochromocytoma.

A 27-year-old male experienced a bladder metastasis of a malignant extra-adrenal retroperitoneal pheochromocytoma 10 months after surgical resection of the primary tumor. This recurrence was managed successfully utilizing a robotic-assisted partial cystectomy with minimal morbidity and negative surgical margins. This is the first published report of robotic-assisted management of bladder pheochromocytoma.

Magnetic resonance angiography for the nonpalpable testis: a cost and cancer risk analysis.

PURPOSE: For the unilateral nonpalpable testis standard management is open surgical or laparoscopic exploration. An ideal imaging technique would reliably identify testicular nubbins and safely allow children to forgo surgical exploration without compromising future health or fertility. Our goal was to perform a cost and risk analysis of magnetic resonance angiography (MRA) for unilateral nonpalpable cryptorchid testes. MATERIALS AND METHODS: A search of the English medical literature revealed 3 studies addressing the usefulness of MRA for the nonpalpable testicle. We performed a meta-analysis and applied the results to a hypothetical set of patients using historical testicular localization data. Analysis was then performed using 3 different management protocols-MRA with removal of testicular nubbin tissue, MRA with observation of testicular nubbin tissue and diagnostic laparoscopy. A cancer risk and cost analysis was then performed. RESULTS: MRA with observation of testicular nubbin tissue results in 29% of patients avoiding surgery without any increased cost of care. Among the 29% of boys with testicular nubbins left in situ and observed the highest estimated risk was 1 in 300 of cancer developing, and 1 in 5,300 of dying of cancer. CONCLUSIONS: A protocol using MRA with observation of inguinal nubbins results in nearly a third of boys avoiding surgical intervention at a similar cost to standard care without any significant increased risk of development of testis cancer.

Plasma cell infiltration of the urinary bladder.

We report a novel entity of plasma cell bladder infiltration without other demonstrable disease. The patient had severe irritative voiding symptoms, hematuria, and a diffuse mucosal infiltrate with 90% plasma cells. Although the patient demonstrated some clinical and pathologic evidence consistent with interstitial cystitis and eosinophilic cystitis, a predominant finding of focal plasma cell infiltration of the urinary bladder suggests a new or previously unrecognized clinical entity.

Granulocytic sarcoma of the testis.

Granulocytic sarcoma is a rare tumor composed of neoplastic blood cells, typically occurring during the course of, or before the onset of, acute nonlymphoblastic leukemia. We present a case of a 37-year-old man with acute testicular pain who was found to have a testicular mass diagnosed as granulocytic sarcoma (GS). Because GS virtually always progresses to leukemia, he underwent postoperative radiotherapy and chemotherapy. He was free of disease 6 months after treatment. This case highlights a rare hematologic cancer that urologists and pathologists should be aware of because it can present as a testicular mass.

Renal tumors in young adults.

PURPOSE: The clinical and pathological features of solid or complex cystic renal masses in young adults have not been defined. We present our experience with patients 17 to 45 years old with such renal masses to define the incidence of malignant vs benign lesions, familial tendencies and clinical outcomes. MATERIALS AND METHODS: The medical records of all patients 17 to 45 years old who presented with a solid or suspicious complex cystic renal mass at 2 tertiary care hospitals between 1988 and 2002 were retrospectively reviewed. Pertinent clinical information was compiled, including age, gender, mode of presentation, renal function, year and type of surgery, pathological analysis and survival data. RESULTS: There were 114 evaluable patients who underwent a total of 119 nephrectomies. Mean patient age was 37.1 years and males comprised 56.1% of the population. Twelve patients had familial renal cell carcinoma (RCC), the von Hippel-Lindau syndrome. Mode of presentation for patients with sporadic disease was symptomatic (55.9%), incidental (35.3%) or unknown (8.8%). Radical nephrectomy, partial nephrectomy and nephroureterectomy were performed in 80 kidneys (67.2%), 37 (31.1%) and 2 (1.7%), respectively. Malignant lesions comprised 79.8% of all masses and 95.8% of these were renal cell carcinoma. Of the RCCs 75.8% were grade 1 or 2 and 89% were organ confined. Young women were much more likely than men to have a benign lesion (36.0% vs 9.5%, p <0.01) and the diversity of histologies was impressive (of the 24 total benign masses 9 were different tumor types). With an average followup of 38.3 months overall survival is 90.2%. Among patients with RCC 84.9% are alive and cancer-free, 11.6% are dead from disease and 3.5% are alive with recurrent disease. CONCLUSIONS: We report the largest known series of solid or suspicious complex renal masses in young adults. As expected, familial tumors are more common in this population. While RCC is the most common tumor, a wide variety of potential pathological outcomes are possible, particularly in women, who were much more likely to have a benign lesion. RCC in this patient population appears to have a favorable prognosis, despite symptomatic presentation in the majority of cases.

Nitric oxide contributes to the rise in forearm blood flow during mental stress in humans.

1. Our aim was to determine whether the vasodilating substance nitric oxide (NO) contributes to the rise in forearm blood flow observed during mental stress in humans. We also determined whether the NO might be released as a result of cholinergic stimulation of the vascular endothelium. 2. Blood flow was measured in both forearms using plethysmography during several 3-5 min bouts of a colour word test. In one forearm the nitric oxide synthase blocker NG-monomethyl-L-arginine (L-NMMA) and other drugs were infused via a brachial artery catheter. The contralateral forearm served as a control. 3. When L-NMMA was given prior to mental stress it blunted the rise in blood flow in the treated forearm almost completely. The normal blood flow response returned during a second bout of stress conducted after a wash-out period. During a third bout of mental stress, administration of more L-NMMA again blunted the blood flow responses to mental stress. 4. When atropine was given prior to mental stress, the increases in blood flow were reduced in the treated forearm. Subsequent administration of both atropine and L-NMMA caused a somewhat greater reduction in the blood flow responses than those observed with atropine alone. 5. These data demonstrate that NO plays a role in forearm vasodilatation during mental stress in humans. It is likely that most of the NO is released by cholinergic stimulation of the vascular endothelium.