Folding Free Energy Determination of an RNA Three-Way Junction Using Fluctuation Theorems.

Nonequilibrium work relations and fluctuation theorems permit us to extract equilibrium information from nonequilibrium measurements. They find application in single-molecule pulling experiments where molecular free energies can be determined from irreversible work measurements by using unidirectional (e.g., Jarzynski's equality) and bidirectional (e.g., Crooks fluctuation theorem and Bennet's acceptance ratio (BAR)) methods. However, irreversibility and the finite number of pulls limit their applicability: the higher the dissipation, the larger the number of pulls necessary to estimate ΔG within a few kBT. Here, we revisit pulling experiments on an RNA three-way junction (3WJ) that exhibits significant dissipation and work-distribution long tails upon mechanical unfolding. While bidirectional methods are more predictive, unidirectional methods are strongly biased. We also consider a cyclic protocol that combines the forward and reverse work values to increase the statistics of the measurements. For a fixed total experimental time, faster pulling rates permit us to efficiently sample rare events and reduce the bias, compensating for the increased dissipation. This analysis provides a more stringent test of the fluctuation theorem in the large irreversibility regime.

Benefit of a more extended pelvic lymph node dissection among patients undergoing radical prostatectomy for localized prostate cancer: A causal mediation analysis.

BACKGROUND: The therapeutic role of extended (ePLND) versus nonextended pelvic lymph node dissection (nePLND) to remove occult micrometastases in men undergoing radical prostatectomy for localized prostate cancer (PC) is conflicting. Therefore, our aim was to quantify the direct effect of ePLND versus nePLND (removal of occult micrometastases), which is not mediated through the detection of nodal disease and potential adjuvant therapy (indirect effect). METHODS: Retrospective, bi-center cohort study of consecutive patients undergoing radical prostatectomy and PLND for PC (January 2006 and December 2016). Patients were followed until April 2018 for the occurrence of either biochemical recurrence or secondary therapy (composite outcome). ePLND was compared to nePLND by unweighted and weighted survival analysis (total effect) as well as by causal mediation analysis (direct and indirect effect). RESULTS: Positive nodal disease was detected in 71 (7%) out of 1008 patients undergoing radical prostatectomy and PLND for PC (ePLND: 368 [36.5%]; nePLND: 640 [63.5%]). Survival analysis demonstrated results in favor of ePLND (unweighted hazard ratio: 0.77 [95% confidence interval: 0.59-1.01], p = .056; weighted hazard ratio: 0.75 [0.56-0.99], p = .044). The causal mediation analysis confirmed the total effect of 0.77 (0.71-0.82). After disentangling this total effect into an indirect effect (via detection of nodal disease and potential adjuvant therapy) and a direct effect (via removal of occult micrometastases), we identified an even more protective direct effect of 0.69 (0.63-0.75). CONCLUSIONS: Our results not only indicate the utility of ePLND but also that its impact is not restricted to a staging benefit and probably involves a therapeutic benefit mediated through the removal of occult micrometastases.

A High Percent Free Prostate Specific Antigen in the Setting of Biochemical Recurrence after Radical Prostatectomy is Associated with Poorer Outcomes: A Validation Study Using Prospectively Collected Biobank Specimens.

PURPOSE: The role of percent free prostate specific antigen (%fPSA) in patients who have undergone radical prostatectomy and subsequently experienced disease relapse is unclear. We previously conducted 2 retrospective studies and found %fPSA 15 or greater in the setting of biochemical recurrence confers more aggressive disease. To validate that finding we used biobank specimens collected prospectively when patients were first diagnosed with biochemical recurrence. MATERIALS AND METHODS: Biobank specimens of patients with undetectable prostate specific antigen after radical prostatectomy and subsequent biochemical recurrence (prostate specific antigen 0.1 ng/ml or greater) were analyzed for %fPSA. Patients were stratified according to the %fPSA cutoff of 15. Univariable and multivariable logistic regression analysis was performed to predict covariates associated with a higher %fPSA. Cox proportional hazard models were performed to evaluate the prognostic effect of %fPSA on androgen deprivation therapy-free survival, metastasis-free survival, castration resistant-free survival and cancer specific survival. RESULTS: A total of 154 men were included in the study, of whom 126 (82%) had %fPSA less than 15 and 28 (18%) had %fPSA 15 or greater. Median followup for %fPSA less than 15 and %fPSA 15 or greater was 75 and 69 months, respectively. Patients with %fPSA 15 or greater had increased hazard of receiving androgen deprivation therapy (43% vs 25%, adjusted HR 2.40, 95% CI 1.12-5.11), metastatic disease (21% vs 7.9%, adjusted HR 4.10, 95% CI 1.11-15.2) and castration resistant prostate cancer (14% vs 4.0%, unadjusted HR 4.14, 95% CI 1.11-15.5) vs %fPSA less than 15, respectively. CONCLUSIONS: Patients with %fPSA 15 or greater were started on androgen deprivation therapy earlier, and they had progression to castration resistant prostate cancer and metastatic stage earlier. %fPSA 15 or greater in the setting of biochemical recurrence after radical prostatectomy is an indicator of a more aggressive disease. Unlike in the diagnostic setting, a higher %fPSA portends a worse clinical outcome.

Salvage radical prostatectomy following focal therapy: functional and oncological outcomes.

OBJECTIVES: To report the oncological and functional outcomes of salvage radical prostatectomy (sRP) after focal therapy (FT). PATIENTS AND METHODS: A retrospective review of all patients who underwent sRP after FT was performed. Clinical and pathological outcomes focussed on surgical complications, oncological, and functional outcomes. RESULTS: In all, 34 patients were identified. The median (interquartile range [IQR]) age was 61 (8.25) years. FT modalities included high-intensity focussed ultrasound (19 patients), laser ablation (13), focal brachytherapy (one) and cryotherapy (one). The median (IQR) time from FT to recurrence was 10.9 (17.6) months. There were no rectal or ureteric injuries. Two (5.9%) patients had iatrogenic cystotomies and four (11.8%) developed bladder neck contractures. The mean (sd) hospital stay was 2.5 (2.1) days. The T-stage was pT2 in 14 (41.2%) patients, pT3a in 16 (47.1%), and pT3b in four (11.8%). In all, 13 (38%) patients had positive surgical margins (PSMs). Six (17.6%) patients received adjuvant radiotherapy (RT). At a mean follow-up of 4.3 years, seven (20.6%) patients developed biochemical recurrence (BCR), and of these, six (17.6%) patients required salvage RT. PSMs were associated with worse BCR-free survival (hazard ratio 6.624, 95% confidence interval 2.243-19.563; P < 0.001). The median (IQR) preoperative International Prostate Symptom Score and International Index of Erectile Function score was 7 (4.5-9.5) and 23.5 (15.75-25) respectively, while in the final follow-up the median (IQR) values were 7 (3.5-11) and 6 (5-12.25), respectively (P = 0.088 and P < 0.001). At last follow-up, 31 (91.2%) patients were continent, two (5.9%) had moderate (>1 pad/day) incontinence, and one (2.9%) required an artificial urinary sphincter. CONCLUSIONS: sRP should be considered as an option for patients who have persistent clinically significant prostate cancer or recurrence after FT. PSMs should be recognised as a risk for recurrent disease after sRP.

Gender-based psychological and physical distress differences in patients diagnosed with non-metastatic renal cell carcinoma.

OBJECTIVES: To analyze gender-based differences in distress symptoms in patients with non-metastatic renal cell carcinoma (RCC) at different stages of disease. METHODS: The Edmonton Symptom Assessment System-revised (ESAS-r) questionnaire includes a physical (PHSDSS) and a psychological distress sub-score (PDSS). The ESAS-r was used to measure psychological and physical distress symptoms in localized RCC patients in a major cancer referral center between 2014 and 2017 at four predefined time points: (a) diagnosis, (b) biopsy, (c) surgery, and (d) last follow-up. Results were gender stratified, and multivariable linear regression models were used to determine associations with increased sub-scores. RESULTS: Overall, 495 patients were included with 37.2% females. No significant gender differences were seen in mean age, relevant clinical parameters, and treatment. PDSS was significantly higher in females after diagnosis (8.5 vs. 5.1, p = 0.018), biopsy (8.9 vs. 4.1, p = 0.003), and surgery (6.5 vs. 4.4, p = 0.007), while being similar at the last follow-up. The multivariable model demonstrated a statistically significant association of female gender with higher PDSS after diagnosis (B = 3.755, 95% CI 0.761-6.750), biopsy (B = 6.076, 95% CI 2.701-9.451), and surgery (B = 1.974, 95% CI 0.406-3.542). PHSDSS was significantly higher in females after biopsy (10.0 vs. 5.7, p = 0.028) and surgery (8.6 vs. 6.1, p = 0.022). In the multivariable model, female gender conferred a higher PHSDSS only after surgery (B = 2.384, 95% CI 0.208-4.560). CONCLUSIONS: Gender-associated psychological distress differences exist in non-metastatic RCC patients throughout treatment, while dissipating at last follow-up. Emphasis should be placed on screening for distress symptoms and providing psychological support continuously, particularly for female patients.

Photoselective vaporization of the prostate: study outcomes as a function of risk of bias, conflicts of interest, and industrial sponsorship.

PURPOSE: To investigate the outcomes of comparative studies on photoselective vaporization of the prostate (PVP) as a function of risk of bias (RoB), conflicts of interest (COI), and industrial sponsorship (IS). METHODS: We performed a systematic literature search for comparative studies on PVP [randomized controlled trials (RCTs) and non-randomized comparative studies (NRCSs)]. Study selection as well as comprehensive assessment of RoB, COIs, and IS were performed in duplicate. The identified studies were further rated by two independent board-certified urologists as either PVP-favourable or PVP-unfavourable. Descriptive statistics were performed among all identified studies and among the subgroups of studies rated as favourable and unfavourable, respectively. RESULTS: Sixty-five studies qualified for inclusion (25 RTCs and 40 NRCSs) of which 56 (86%) were rated favourable and 9 (14%) unfavourable. A majority of all studies mentioned the absence/presence of potential COIs (78%). In contrast, a sponsorship statement was only found in 29% of the investigations. Studies rated favourable demonstrated a higher percentage of COIs (39% versus 22%). IS was exclusively found among favourable studies. Furthermore, a serious or critical RoB was more often found in favourably rated NRCSs. CONCLUSIONS: COIs and IS seem to be associated with favourable study outcomes in comparative studies on PVP. The transparency of the whole research process from study conception to the dissemination of the results has to be further improved to prevent a harmful effect of COIs and IS on the internal validity of studies.

Predictors of prostate-specific antigen testing in men aged ≥55 years: A cross-sectional study based on patient-reported outcomes.

OBJECTIVES: To examine the predictors of prostate-specific antigen discussion with a physician and prostate-specific antigen testing in men aged ≥55 years. METHODS: Utilizing the USA Health Information National Trends Survey, 4th Ed., a cross-sectional study from 2011 to 2014 was carried out to analyze the factors predicting prostate-specific antigen testing and discussion in men ≥55 years. Associations between each covariate and prostate-specific antigen discussion/testing were determined. Multivariable logistic regression models were used to determine clinically relevant predictors of prostate-specific antigen discussion/testing. Due to multiple comparisons, the Bonferroni correction was used. RESULTS: A total of 2731 men included in the Health Information National Trends Survey were analyzed. Several socioeconomic parameters were found to increase the likelihood of men aged ≥55 years to undergo prostate-specific antigen testing: living with a spouse, a higher level of education (college graduate or above), a higher income (>$50 000 annually) and previous history of any cancer. In contrast, current smokers were less likely to undergo prostate-specific antigen testing. Having a prostate-specific antigen discussion with a physician was more likely for men surveyed in 2014, for men who were living with a spouse, who had a higher annual income (>$50 000 annually) and those with a history of any cancer. CONCLUSIONS: Significant inequalities in prostate-specific antigen testing and discussion exist among men in the USA, mainly driven by socioeconomic factors. Ideally, prostate-specific antigen testing and discussion should be based on relevant clinical factors with a shared decision-making approach for every man. Therefore, a better understanding of the socioeconomic factors influencing prostate-specific antigen testing/discussions can inform strategies to reduce existing gaps in care.

The who, when, and why of primary adrenal malignancies: Insights into the epidemiology of a rare clinical entity.

BACKGROUND: Primary malignancies of the adrenal glands are rare. Epidemiologic assessment of primary adrenal malignancies is lacking and has been limited to case reports and series. Population-level data can provide a better understanding of the incidence, distribution, and prognostic factors associated with these rare malignancies. METHODS: The Surveillance, Epidemiology, and End Results database (1973-2013) was queried for all patients who were diagnosed with primary adrenal malignancies, categorized in 5 histologic groups: adrenocortical carcinoma (ACC), pheochromocytoma and paraganglioma (PH), neuroblastoma (NE), non-Hodgkin lymphoma (NHL), and sarcoma (SA). Age-adjusted incidence, distribution trends, and cancer-specific survival (CSS) for each group were analyzed. RESULTS: In total, 4695 patients with primary adrenal malignancies were identified, including 2057 with ACC, 512 with PH, 1863 with NE, 202 with NHL, and 61 with SA. The age-adjusted incidence of all 5 histologic subtypes was rising. Age at presentation differed substantially by histologic group: NE was the most prevalent during the first decade of life, whereas ACC predominated after age 30 years, and NHL outnumbered PH after age 70 years. Patient-specific factors were not associated with advanced disease at the time of presentation. The 5-year CSS rate for each histologic subtype was 38% for ACC, 69% for PH, 64% for NE, 38% for NHL, and 42% for SA. Survival outcomes for patients with ACC, NHL, PH and SA remained unchanged over the 40-year study period. Multimodal therapy was associated with higher CSS in patients with NE. CONCLUSIONS: This first population-level analysis of all primary adrenal malignancies provides important initial data regarding presentation and clinical outcomes. Notably, except for patients with NE, the survival of patients with these rare cancers has not improved over the past 40 years.

Renal tumor biopsy: indicators, technique, safety, accuracy results, and impact on treatment decision management.

CONTEXT: Renal tumor biopsy (RTB), as distinct from the more common renal biopsy for medical renal disease, is an option for patients with renal masses. It is mainly used for small renal masses (SRM) but it may also be indicated for larger masses and even in the presence of metastatic disease. Its main indication in SRM is to avoid intervention for benign kidney tumors but increasingly enables more personalized treatment for kidney cancer patients. OBJECTIVE: The objective of this paper is to provide a comprehensive review of the most recent literature available for RTB including the indications, the technique and also the possible complications. RESULTS: The urological community continues to optimize the indications for RTB. Non-operative treatment modalities, such as active surveillance, ablative modalities, and immunotherapy, may have different results influenced by tumor histology. Continuing concern regarding complications and accuracy and, therefore, the utility of RTB has been addressed. Recent reports support the potential benefit of RTB, safely avoiding a significant number of interventions with good results and minimal complications. CONCLUSION: Urologists should be aware of the benefits of RTB and develop experience with this technique to optimize the results. This diagnostic strategy should be discussed with patients and adopted as it has been with other solid tumors.

Smarter screening for prostate cancer.

PURPOSE: Prostate cancer is the second commonest cancer among men. In the large European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, prostate-specific antigen (PSA) screening has been shown to substantially reduce prostate cancer mortality. However, PSA screening is known to lead to more unnecessary prostate biopsies and over-diagnosis of clinically insignificant cancer. Therefore, it is imperative that smarter screening methods be developed to overcome the weaknesses of PSA screening. This review explores the novel screening tools that are available. METHODS: A comprehensive literature search was performed using PubMed regarding newer biomarkers, imaging techniques and risk-predicting models that are used to screen for prostate cancer in mainly biopsy-naïve men. RESULTS: Novel serum-based models like 4Kscore® and prostate health index (PHI) are generally better than PSA alone in detecting clinically significant cancer. Similarly, urine-based biomarkers like prostate cancer antigen 3 (PCA3) and HOXC6/DLX1 have been shown to be more accurate than PSA screening. More recently, multiparametric magnetic resonance imaging (mpMRI) is gaining popularity for its ability to detect clinically significant cancer. There is also evidence that combining individual tests to develop prediction models can reliably predict high-risk prostate cancers while reducing the number of unnecessary biopsies. Combinations such as the Stockholm-3 model (STHLM3) and other novel combinations are presented in this review. CONCLUSION: While we continue to find the smarter screening methods that are reliable, precise, and cost-effective, we continue to advocate shared decision-making in prostate cancer screening in order to work in our patients' best interests.

Future developments in ureteral stents.

PURPOSE OF REVIEW: We present a review of recent literature to summarize the most recent evidence on the use of ureteral stents, including the use of different materials and treatment of stent-related symptoms. RECENT FINDINGS: Metal stents are able to resist lumen occlusion from extrinsic compression allowing longer indwelling time and making them an option for long-term use. Biodegradable stents have the advantage not to require secondary procedures; however, they have not proven their safety in the clinical setting yet. Coated and drug-eluting stents seem to be promising concepts to prevent stent-related symptoms, but still have to be considered as experimental approaches. The most commonly used stent type is the standard double J stent, named for its J-shaped curled ends and manufactured from polyurethane, silicone or various polymers. SUMMARY: After more than 5 decades of using stents there are promising advancements in their designs and materials aiming to maintain their patency and control stent-related symptoms. Long-term metallic stents and coated stents are good options that should be considered in selected patients. Biodegradable stents are promising developments but not sophisticated yet. Pain medication, alpha-blocker and antimuscarinic medications are still frequently used and necessary. Treatment combinations can result in better outcomes than monotherapy.

[Jejunal phlebectasia as a cause of massive gastrointestinal haemorrhage]. / Flebectasia yeyunal como causa de hemorragia digestiva media masiva.

Vascular abnormalities of the gastrointestinal tract are a common cause of gastrointestinal bleeding. Most of them are located within the reach of the upper endoscopy or colonoscopy, although once discarded, it forces to consider small bowel as the source of bleeding. The successful management of a gastrointestinal bleeding depends mainly on the timely location of the source of bleeding. Nevertheless this task can be difficult when the cause is not within the reach of conventional methods. We present a case of a 21 year-old men in which the diagnosis of bleeding yeyunal phlebectasia was made by the findings of the capsule endoscopy and laparoscopy.

Roles for active surveillance in renal cancer.

PURPOSE OF REVIEW: With this review, we describe the most recent advances in active surveillance as well as diagnosis and management of small renal masses (SRMs). RECENT FINDINGS: We discuss diagnosis, differentiation of solid from cystic lesions, risk prediction and treatment of the SRM. A better understanding of the disease facilitates the use of more conservatory treatments, such as active surveillance. Active surveillance has been increasingly accepted not only for SRM, but also for larger tumors and even metastatic patients. Exiting advances in risk prediction will help us define which patients can be safely managed with active surveillance and which require immediate treatment. Meanwhile, the use of renal tumor biopsies is still an important tool for these cases. SUMMARY: Active surveillance is an option for many patients with renal masses. Noninvasive methods for diagnosis and risk prediction are being developed, but meanwhile, renal tumor biopsy is a useful tool. A better understanding of the disease increases the number of patients who can undergo active surveillance fully certain of the safety of their management.

Prevalence and variables associated with an abnormal ankle-brachial index among patients with human immunodeficiency virus/acquired immunodeficiency syndrome.

Objectives The longer survival of patients with human immunodeficiency virus/acquired immunodeficiency syndrome and the introduction of the highly active antiretroviral therapy have increased the number of chronic conditions; among these, cardiovascular diseases. The aim of this study is to determine patient, disease, and factors associated with peripheral arterial disease in a population of patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Methods A prospective nested case-control study of a cohort of patients with human immunodeficiency virus/acquired immunodeficiency syndrome was conducted in a tertiary medical center in Mexico City. A sample size of 206 patients was calculated. Medical history, relevant laboratory data, peripheral arterial exam, and screening ankle-brachial index tests were obtained. Results The prevalence of abnormal ankle-brachial indexes was 20% (42 patients). Patient's mean age was 44 years ±13. The majority (98.5%) were actively receiving highly active antiretroviral therapy; active smoking was reported in 55 (27%), arterial hypertension and type 2 diabetes mellitus were found in 24 (12%) and 22 (11%) patients. Median time from the human immunodeficiency virus diagnosis was eight years (Interquartile range ±11); the mean CD4 count was 481, with a mean viral load of 13,557 copies (SD ± 69025.27) and 1889.18 (SD ± 9052.77) for patients with normal and abnormal ankle-brachial index and a median of 40 (IQ ± 2). Viral load ( p = 0.04) and number of years with human immunodeficiency virus/acquired immunodeficiency syndrome ( p = 0.04) were significantly associated with abnormal ankle-brachial indexes. Conclusions Abnormal ankle-brachial index seems to be more frequent in Mexican patients with human immunodeficiency virus/acquired immunodeficiency syndrome when compared with the general population at the same age. The most important factors associated with arterial disease were the viral load and the number of years with human immunodeficiency virus/acquired immunodeficiency syndrome. TRIAL REGISTRATION: ClinicalTrials.gov NCT02264509.

Incidence and treatment of malignant tumors of the genitourinary tract in renal transplant recipients.

PURPOSE: To provide data of the incidence and management of common urological malignancies in renal transplant recipients. MATERIALS AND METHODS: We conducted a retrospective analysis of a prospective database from August 1967 to August 2015. A descriptive analysis of the sample was performed. RESULTS: Among 1256 consecutive RTR a total of 88 patients developed malignancies (7%). There were 18 genitourinary tumors in the 16 patients (20.45% of all malignant neoplasms), incidence of 1.27%. The most common neoplasm encounter was renal cancer (38.8%), followed by urothelial carcinoma (33.3%). Median follow up of transplantation was 197 months (R, 36-336). Mean time from RT to cancer diagnosis 89±70 months (R, 12-276). CsA and AZA was the most common immunosuppression regimen in 68.75%. Mean follow-up after diagnosis was 103±72 months (R 10-215). Recurrence free survival rate of 100%. Overall survival of 89.5% of the sample; there were two non-related cancer deaths during follow up. CONCLUSIONS: The incidence of neoplasms in RTR was lower than in other series, with favorable functional and oncologic results after treatment. This suggests that actions to reduce the risk of these malignancies as well as a strict follow-up are mandatory for an early detection and treatment.

The correlation between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED): results from a survey in males from Mexico City (MexiLUTS).

INTRODUCTION: ED and LUTS affect a high proportion of male population. Although Hispanics are suspected to have a higher risk of experiencing LUTS, detailed information on its frequency and association with ED in this population is scarce. OBJECTIVE: To determine the frequency of LUTS and ED, and its correlation in Mexican males. METHODS: A cross-sectional analytical survey was answered by 1041 men. It included the International Prostate Symptom Score and the quality of life question (IPSS/QoL); International Index of Erectile Function (IIEF-5); the short form of the International Consultation of Incontinence Questionnaire (ICIQ-SF); and demographic data. For the analysis, we divided our population into 2 groups (18-39 and 40 and older), and then an exploratory correlation analysis was performed to search for significant differences among IPSS severity groups, and finally a multivariate regression model was applied. RESULTS: Mean age was 48.6 ± 14.5 years. One hundred twenty-three individuals (11.8 %) were asymptomatic, and 611 (58.7 %) had mild, 226 (21.7 %) had moderate, and 81 (7.8 %) had severe IPSS score. The most common symptoms were nocturia (72.4 %), increased urinary frequency (58.3 %), and slow urinary stream (42.6 %). Two hundred fifty-eight (24.7 %) complained of incontinence. Of 765 individuals, 484(63.2 %) reported some degree of ED. Severe LUTS, DM, and age were independent risk factors for ED severity. CONCLUSION: LUTS and ED may represent one of the largest sources of morbidity in our population, and their association was demonstrated. Awareness on these entities should be raised, and further research is required to determine the higher frequency of LUTS and ED in Hispanics.

Validating the total cancer location density metric for stratifying patients with low-risk localized prostate cancer at higher risk of grade group reclassification while on active surveillance.

PURPOSE: To validate a previously proposed prognostic metric, Total Cancer Location (TCLo) density, in a contemporary cohort of men with grade group (GG) 1 prostate cancer (PCa) on active surveillance (AS). METHODS: We evaluated 123 patients who entered AS with maximum GG1 PCa at diagnostic and/or confirmatory biopsy. TCLo was defined as the total number of PCa locations identified on both biopsy sessions. TCLo density was calculated as TCLo / prostate volume [ml]. Primary endpoint was progression-free survival (PFS), defined as time from confirmatory biopsy to grade group reclassification (GGR) on repeat biopsy or prostatectomy. Optimal cut-point for TCLo density was predefined in a previously reported cohort and applied to this contemporary cohort. Kaplan-Meier and multivariable Cox regression analysis were used to estimate the association of predictors with PFS. RESULTS: During median follow-up of 7.8 years, (IQR 7.3-8.2) 34 men had GGR. Using previously defined cut-points, PFS at 5-years was 60% (95% CI: 44%-81%) vs. 89% (95% CI: 83%-96%) in men with high (≥0.06 ml-1) vs. low (<0.06 ml-1) TCLo density, and 63% (95% CI: 48%-82%) vs. 90% (95% CI: 83%-96%) in men with high (≥3) vs. low (≤2) TCLo (log-rank test: P < 0.0001, respectively). Adjusting for age, prostate volume, percent of positive cores and PSA, both higher TCLo density (HR [per 0.01 ml-1 increase]: 1.18, 95% CI: 1.05-1.33, P = 0.005) and TCLo (HR: 1.69, 95% CI: 1.20-2.38, P = 0.002) were associated with shorter PFS. CONCLUSION: The previously suggested prognostic value of TCLo density was confirmed in this validation cohort. TCLo alone performed similarly well. Patients with high TCLo density (≥0.06 ml-1) or TCLo (>2) were at greater risk of GGR while on AS. With external validation, these metric may help guide risk-adapted surveillance protocols.

Age related differences in primary testicular lymphoma: A population based cohort study.

INTRODUCTION: Primary testicular non-Hodgkin's lymphoma (PTL) is a very rare disease, comprising 1% of all non-Hodgkin's lymphoma and <5% of all cases of testicular tumors. With a median age at diagnosis of 67 years, PTL is the most common testicular malignancy in men aged >60 years. There is limited published data on PTL incidence and outcomes in younger patients. The aim of this study is to compare the clinical parameters and survival outcomes between the patients older and younger than 50. METHODS: The SEER database was queried for all patients diagnosed with PTL between 1983 and 2017. Data collected consisted of demographic, and clinical parameters, including staging, pathological assessments, and survival data. Patients were stratified according to their age and compared. RESULTS: There was a total of 1,581 patients diagnosed with PTL between the year 2000 and 2017, of whom 215 (13.6%) were younger than 50 years old. The median age at diagnosis was 41 (interquartile range [IQR] 1-50), and 72 (IQR 51-95) years old for patients ≤50 and patients > 50 years of age, respectively. Comparison of younger and older patients detected similarities in disease laterality (92% vs. 94%, P = 0.38) and Ann Arbor stage I to II at diagnosis (76% vs. 75%, P = 0.59). The most common diffuse large B-cell lymphoma (DLBCL) subtype was more common in older patients (61% vs. 87%, P < 0.001). Radical orchiectomy (71% vs. 79%, P = 0.004) and radiation treatment (40% vs. 37%, P = 0.49) rates were comparable between both groups. However, a higher proportion of younger patients underwent chemotherapy (83% vs. 72%, P < 0.001). Patients ≤50 and >50 years old had a hazard ratio (HR) of 0.63 (95% CI: 0.57-0.71) and 0.34 (95% CI: 0.31-0.37), respectively, for 10-year OS with a median survival time for patients >50 of 5.75 years (95% CI: 5.25-6.33), P < 0.001. Patients ≤50 years old had a HR of 0.33 (95% CI: 0.26-0.40) compared to HR of 0.40 (95% CI: 0.37-0.43) in patients >50 years old for cumulative disease-specific mortality (DSM, P = 0.0204). Age >50 years was associated with worse DSM with a HR of 1.39 (95% CI: 1.05- 1.86, P = 0.024). Ann Arbor stage II and higher was also associated with worse DSM, while undergoing surgery, radiotherapy, and chemotherapy were associated with improved DSM. CONCLUSIONS: PTL is the most common testicular malignancy in men older than 60 years of age, but more than a quarter of the patients are younger than 60 and more than 13% are ≤50 years. Younger patients are more likely to receive chemotherapy and radiation, and overall do better in terms of DSM. Being younger, having a lower Ann Arbor stage and being treated with chemotherapy and radiotherapy increase the chances of survival.

Neoadjuvant Cabazitaxel plus Abiraterone/Leuprolide Acetate in Patients with High-Risk Prostate Cancer: ACDC-RP Phase II Trial.

PURPOSE: Early treatment intensification with neoadjuvant therapy may improve outcomes in patients with high-risk, localized prostate cancer treated with radical prostatectomy. Our objective was to compare pathologic, oncologic, and safety outcomes of neoadjuvant abiraterone acetate plus leuprolide acetate with or without cabazitaxel prior to radical prostatectomy in patients with localized, high-risk prostate cancer. PATIENTS AND METHODS: This open-label, multicenter, phase II trial randomized men with clinically localized, D'Amico high-risk prostate cancer to neoadjuvant abiraterone acetate (1,000 mg/day) and leuprolide acetate (22.5 mg every 3 months) with or without cabazitaxel (25 mg/m2) prior to radical prostatectomy. The primary outcome was pathologic complete response (pCR) or minimal residual disease (MRD). Secondary outcomes included surgical margins, lymph node involvement, pathologic stage, 12-month biochemical relapse-free survival (BRFS) rates, and safety profile. RESULTS: The per-protocol population consisted of 70 patients [cabazitaxel arm (Arm A): 37, no cabazitaxel arm (Arm B): 33]. Median patient age and prostate-specific antigen levels were 63.5 years [interquartile range (IQR), 58.0-68.0] and 21.9 ng/mL (IQR, 14.6-42.8), respectively. pCR/MRD occurred in 16 (43.2%) versus 15 patients (45.5%) in arms A and B, respectively (P = 0.85). pCR occurred in two (5.4%) versus three patients (9.1%) in arms A and B, respectively (P = 0.66). Patients with ≤ 25% total biopsy cores positive had increased odds of pCR/MRD (P = 0.04). Patients with pCR/MRD had superior 12-month BRFS rates (96.0% vs. 62.0%, P = 0.03). Grade 3+ adverse events occurred in 42.5% and 23.7% of patients in arms A and B, respectively (P = 0.078). CONCLUSIONS: Neoadjuvant cabazitaxel addition to abiraterone acetate/leuprolide acetate prior to radical prostatectomy did not improve pCR/MRD in clinically localized, high-risk prostate cancer.