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Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS 1 ) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS 2 (PHS 1 , adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS 2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10 -180 ). Comparing the 80 th /20 th PHS 2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS 2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

At the Canadian Testis Cancer Workshop, the multidisciplinary management of testis cancer care was discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents, fellows, nurses, patients, and patient advocacy group members.This review summarizes the discussion regarding clinical dilemmas in local and regional testis cancer. We present cases that highlight the need for a coordinated approach to individualize care. Overarching themes include the importance of a multidisciplinary approach to testis cancer, willingness to involve a high-volume experienced center, and given that the oncological outcomes are excellent, a reminder that clinical decisions need to prioritize selecting a strategy with the least treatment-related morbidity when safe.

Active germ cell malignancies express high levels of specific circulating micro-RNAs (miRNAs), including miR-371a-3p (miR371), which is undetectable in teratoma. Teratoma markers are urgently needed for theselection of patients and treatments because of the risk of malignant transformation and growing teratoma syndrome. To assess the accuracy of plasma miR375 alone or in combination with miR371 in detecting teratoma, 100 germ cell tumor patients, divided into two cohorts, were enrolled in a prospective multi-institutional study. In the discovery cohort, patients with pure teratoma and with no/low risk of harboring teratoma were compared; the validation cohort included patients with confirmed teratoma, active germ cell malignancy, or complete response after chemotherapy. The area under the receiver operating characteristic curve values for miR375, miR371, and miR371-miR375 were, respectively, 0.93 (95% confidence interval [CI]: 0.87-0.99), 0.59 (95% CI: 0.44-0.73), and 0.95 (95% CI: 0.90-0.99) in the discovery cohort and 0.55 (95% CI: 0.36-0.74), 0.74 (95% CI: 0.58-0.91), and 0.77 (95% CI: 0.62-0.93) in the validation cohort. Our study demonstrated that the plasma miR371-miR375 integrated evaluation is highly accurate to detect teratoma. PATIENT SUMMARY: The evaluation of two micro-RNAs (miR375-miR371) in the blood of patients with germ cell tumors is promising to predict teratoma. This test could be particularly relevant to the identification of teratoma in patients with postchemotherapy residual disease., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We investigated the prognostic utility of pre-chemotherapy neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic germ cell tumors (GCTs) undergoing first-line chemotherapy. We utilized two institutional databases to analyze the pretreatment-derived NLR (dNLR). Predictive accuracy was evaluated using the Cox proportional hazard model adjusted for the international germ cell cancer collaborative group (IGCCCG) risk classification. Discriminatory accuracy was evaluated by determining the area under the receiver operating characteristic curve (AUROC). In total, 569 of 690 patients had available dNLR (IGCCCG: good, 64%; intermediate, 21%; poor, 16%). The 5-year and 10-year overall survivals (OSs) for good, intermediate, and poor risk groups were 96.2%, 92.8%, and 62.7% and 93.9%, 90.3%, and 62.7%, respectively. A dNLR of 2 provided the best discriminatory accuracy with an AUROC of 0.58 (95% CI: 0.52-0.65, p = 0.01) for progression-free survival (PFS), whereas for OS, a dNLR of 3 provided the best discriminatory accuracy with an AUROC of 0.62 (95% CI: 0.53-0.70, p < 0.01). A dNLR > 2 was associated with a hazard ratio (HR) of 1.99 (95% CI: 1.27-3.12, p < 0.01) for PFS, which lost its effect after adjustment for IGCCCG (HR: 1.44, 95% CI: 0.90-2.30, p = 0.13). For OS, a dNLR >3 was associated with an HR of 3.00 (95% CI: 1.79-5.01, p < 0.01), but lost its effect after adjustment for IGCCCG. Systemic inflammation plays a role in metastatic GCT, but its prognostic utility beyond established algorithms is limited. The general prognostic value of NLR can be seen across a number of tumors, although the consistency and magnitude of the effect differ according to cancer type, disease stage, and treatment received. We identified that an elevated NLR was associated with an adverse PFS and OS, but not independent of the IGCCCG risk classification. dNLRs >2 and >3 were associated with an adverse PFS and OS, respectively, in patients with metastatic GCT receiving first-line chemotherapy, but not independent of the IGCCCG risk classification.

Purpose: Cisplatin is a first-line chemotherapeutic for many cancers, but causes neurotoxicity including hearing loss, tinnitus, and peripheral sensory neuropathy. However, no study has comprehensively characterized risk factors for developing multiple (>1) severe neurotoxicities., Experimental Design: The relationship between multiple severe neurotoxicities and age, cumulative cisplatin dose, medical history, and lifestyle/behavioral factors was evaluated in 300 cisplatin-treated testicular cancer survivors using logistic regression. Case-control genome-wide association study (GWAS; cases, n = 104 and controls, n = 196) was also performed., Results: Age at clinical examination ( P = 6.4 × 10 -16 ) and cumulative cisplatin dose ( P = 5.4 × 10 -4 ) were positively associated with multiple severe neurotoxicity risk, as were high serum platinum levels ( P = 0.02), tobacco use (ever smoker, P = 0.001 and current smoker, P = 0.002), and hypertension ( P = 0.01) after adjustment for age and cumulative cisplatin dose. Individuals with multiple severe neurotoxicities were more likely to experience dizziness/vertigo ( P = 0.01), Raynaud phenomenon ( P = 3.7 × 10 -9 ), and symptoms consistent with peripheral motor neuropathy ( P = 4.3 × 10 -14 ) after age and dose adjustment. These patients also reported poorer overall health ( P = 2.7 × 10 -5 ) and a greater use of psychotropic medications ( P = 0.06). GWAS identified no genome-wide significant SNPs. Gene-based association analysis identified RGS17 ( P = 3.9 × 10 -5 ) and FAM20C ( P = 5.5 × 10 -5 ) as near genome-wide significant. Decreased FAM20C expression was associated with increased cisplatin sensitivity in tumor cell lines., Conclusions: Certain survivors are more susceptible to cisplatin-induced neurotoxicity, markedly increasing likelihood of developing numerous neuro-otological symptoms that affect quality of life. Genome-wide analysis identified genetic variation in FAM20C as a potentially important risk factor., (©2020 American Association for Cancer Research.)

Background: Statins inhibit HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. Epidemiological and pre-clinical evidence support an association between statin use and delayed prostate cancer (PCa) progression. Here, we evaluated the effects of neoadjuvant fluvastatin treatment on markers of cell proliferation and apoptosis in men with localized PCa., Methods: Thirty-three men were treated daily with 80 mg fluvastatin for 4-12 weeks in a single-arm window-of-opportunity study between diagnosis of localized PCa and radical prostatectomy (RP) (ClinicalTrials.gov: NCT01992042). Percent Ki67 and cleaved Caspase-3 (CC3)-positive cells in tumor tissues were evaluated in 23 patients by immunohistochemistry before and after treatment. Serum and intraprostatic fluvastatin concentrations were quantified by liquid chromatography-mass spectrometry., Results: Baseline characteristics included a median prostate-specific antigen (PSA) level of 6.48 ng/mL (IQR: 4.21-10.33). The median duration of fluvastatin treatment was 49 days (range: 27-102). Median serum low-density lipoprotein levels decreased by 35% after treatment, indicating patient compliance. Median PSA decreased by 12%, but this was not statistically significant in our small cohort. The mean fluvastatin concentration measured in the serum was 0.2 μM (range: 0.0-1.1 μM), and in prostatic tissue was 8.5 nM (range: 0.0-77.0 nM). At these concentrations, fluvastatin induced PCa cell death in vitro in a dose- and time-dependent manner. In patients, fluvastatin treatment did not significantly alter intratumoral Ki67 positivity; however, a median 2.7-fold increase in CC3 positivity (95% CI: 1.9-5.0, p = 0.007) was observed in post-fluvastatin RP tissues compared with matched pre-treatment biopsy controls. In a subset analysis, this increase in CC3 was more pronounced in men on fluvastatin for >50 days., Conclusions: Fluvastatin prior to RP achieves measurable drug concentrations in prostatic tissue and is associated with promising effects on tumor cell apoptosis. These data warrant further investigation into the anti-neoplastic effects of statins in prostate tissue.

Introduction: We sought to evaluate the discrepancies between primary pathology report and second pathology review of radical orchiectomy (RO) specimens., Methods: A retrospective review was performed of RO specimens from the Ontario Cancer Registry. All cases required both a primary pathology report and a second pathology review from another institution. Histopathological variables assessed included histological subtype and components of mixed germ cell tumor (GCT), pathological tumor (pT) stage, lymphovascular invasion (LVI), spermatic cord invasion, and surgical margin., Results: Between 1994 and 2015, 5048 ROs were performed with 2719 (53.9%) seminoma and 2029 (40.2%) non-seminoma. Of these, 519 (10.3%) received a second pathology review. There was concordance between primary pathology report and second pathology review in 326 (62.8%) cases. The most common discrepancies involved a change in pT stage (n=148, 28.5%), with upstaging in 83 (16%) and downstaging in 65 (12.5%) cases relative to the original pT stage. The second most common discrepancy regarded the reporting of LVI (n=121, 23.3%), with 62 (11.9%) reporting presence of LVI when the primary pathology report did not. Other discrepancies included a change in the histological subtype in 28 (5.4%) cases and spermatic cord margin status in five (9.6%) cases., Conclusions: Only 10% of orchiectomy specimens underwent a second pathology review, with nearly 40% of reviews leading to a meaningful change in parameters. Such variation could lead to incorrect tumor staging, estimate of relapse risk, and inappropriate treatment decisions. Expert pathology review of RO specimens should be considered, as it has significant implications for decision-making.

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

Purpose: We determined if the "bag squeeze" technique decreases pain during flexible cystoscopy in men., Materials and Methods: This single center, prospective, double-blind, randomized controlled trial recruited 200 consenting participants who were ambulatory, outpatient males who had undergone prior cystoscopy and were not expected to require any secondary procedures. Men with prior urethral stricture or bladder neck contracture were excluded from study. Once eligibility was assessed and consent obtained, participants were randomized to undergo cystoscopy with the bag squeeze (group A) or the sham bag squeeze procedure (group B). Following cystoscopy, participants completed a pain questionnaire (visual analogue scale). Differences in mean pain score between groups were evaluated using Students' t-test with a 2-sided alpha of 0.05., Results: A total of 200 patients were randomized and underwent flexible cystoscopy. Ten participants were ineligible because they required secondary procedures. Among the 190 eligible patients 97 were randomized to bag squeeze (group A) and 93 to sham bag squeeze (group B) with mean pain scores of 1.91 and 3.39, respectively (p <0.005)., Conclusions: This study demonstrated a clinically meaningful decrease in pain for men undergoing flexible cystoscopy when the irrigation bag squeeze technique was used vs placebo bag squeeze. Accordingly, this useful, simple and free method to improve patient comfort during flexible cystoscopy should be adopted by clinicians.

At the Canadian Testis Cancer Workshop, the rationale and feasibility of regionalization of testis cancer care were discussed. The two-day workshop involved urologists, medical and radiation oncologists, pathologists, radiologists, physician's assistants, residents and fellows, and nurses, as well as patients and patient advocacy groups.This review summarizes the discussion and recommendations of one of the central topics of the workshop - the centralization of testis cancer in Canada. It was acknowledged that non-guideline-concordant care in testis cancer occurs frequently, in the range of 18-30%. The National Health Service in the U.K. stipulates various testis cancer care modalities be delivered through supra-regional network. All cases are reviewed at a multidisciplinary team meeting and aspects of care can be delivered locally through the network. In Germany, no such network exists, but an insurance-supported online second opinion network was developed that currently achieves expert case review in over 30% of cases. There are clear benefits to regionalization in terms of survival, treatment morbidity, and cost. There was agreement at the workshop that a structured pathway for diagnosis and treatment of testis cancer patients is required.Regionalization may be challenging in Canada because of geography; independent administration of healthcare by each province; physicians fearing loss of autonomy and revenue; patient unwillingness to travel long distances from home; and the inability of the larger centers to handle the ensuing increase in volume. We feel the first step is to identify the key performance indicators and quality metrics to track the quality of care received. After identifying these metrics, implementation of a "networks of excellence" model, similar to that seen in sarcoma care in Ontario, could be effective, coupled with increased use of health technology, such as virtual clinics and telemedicine.

Immobilization systems and their corresponding set-up errors influence the clinical target volume to the planning target volume (CTV-PTV) margins, which is critical for hypofractionated prostate stereotactic body radiotherapy (SBRT). This preliminary study evaluates intrafraction prostate displacement for two immobilization systems (A and B). Six consecutive patients having localized prostate cancer and implanted prostate marker seeds were studied. Planar X-ray images were acquired pre- and post-treatment to find the intrafraction prostate displacement. The average absolute displacements (lateral, longitudinal, vertical) were 0.9 ± 0.4 mm, 1.7 ± 0.1 mm, 1.3 ± 0.3 mm (system A), and 0.5 ± 0.2 mm, 0.6 ± 0.1 mm, 0.8 ± 0.3 mm (system B), with average three-dimensional displacements of 2.6 ± 0.2 mm (system A) and 1.3 ± 0.2 mm (system B). The computed CTV-PTV margins (lateral, longitudinal, vertical) were 2.5 mm, 2.5 mm, 3.6 mm and 1.4 mm, 1.6 mm, 2.4 mm for systems A and B, respectively. This suggests that the immobilization system influences intrafraction prostate displacement and, therefore, the margins applied. However, the margins found for both systems are comparable to the margins used for hypofractionated prostate SBRT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Mostafaei et al.)

Virtual care models for cancer survivorship are needed to support patients living with the chronic effects of cancer treatment, while increasing health system capacity. Characteristics that may be critical to their success have not been adequately studied. This scoping review summarizes previous efforts to virtualize survivorship care to inform future innovations in the field. Four databases were searched for articles published before January 2020, and 24 articles that met selection criteria were included in this analysis. Rationale for pursuing virtual models of care shared two common objectives: (1) the need for sustainable survivorship care, and (2) the opportunity to improve survivorship outcomes. Breast cancer ( N  = 10) and prostate cancer ( N  = 4) were the most targeted cancers for virtual survivorship care. The implemented technologies included web platforms ( N  = 15), telephone calls ( N  = 12), and smartphone or tablet applications ( N  = 5). A variety of healthcare professionals were effectively involved in the provision of virtual care. Future virtual care models may benefit from integrating with existing health systems and services, repurposing common technologies, involving allied health professionals, and engaging patients and caregivers from diverse communities in the design of virtual services., Competing Interests: Competing InterestsAll authors are involved in the design, development, and evaluation of the Ned prostate cancer survivorship platform described in the manuscript. J.A.C. and A.F. own intellectual property rights to Ned and are entitled to personally benefit from any commercial use of the intellectual property., (© The Author(s) 2020.)

With the implementation of the Affordable Care Act (ACA), many homeless persons who previously lacked health insurance gained medical coverage. This paper describes the experiences of homeless persons in accessing and using primary care services, post-implementation of the ACA. Twenty-six semi-structured interviews were completed with homeless persons and primary care providers/staff. Via thematic analysis, themes were identified, categorized by: factors which influence primary care access and use patterns, and strategies to promote consistent primary care use. Maintaining insurance and leveraging systems-based strategies to support primary care access and use may address health disparities and promote health equity.

Purpose: To compare the psychological distress throughout several predefined disease time points in patients younger than 70 with small renal masses (SRMs) treated with either active surveillance (AS) or ablative/surgical therapy., Methods: Using the Edmonton Symptom Assessment System - revised (ESAS-r) questionnaire, we focused on psychological distress symptoms in all consecutive patients with an SRM between 2014 and 2017. We further evaluated the psychological distress sub-score (PDSS) of ESAS-r, consisting of the sum scores of anxiety, depression, and well-being. PDSS of patients treated with AS or ablation/surgery were compared at 4 distinct time points (before and after diagnosis, after a biopsy is performed, and at last follow-up). Multivariable linear regression models were performed to assess factors associated with worse PDSS (1-point score increase)., Results: We examined 477 patients, of whom 217 and 260 were treated with AS and surgery/ablation, respectively. Similar ESAS-r and PDSS scores were shown at all predefined disease time points except following an SRM biopsy and at last, follow-up, where AS-treated patients with a biopsy-proven malignancy had significantly worse PDSS (11.4 vs. 6.1, P = 0.035), and (13.2 vs. 5.4, P = 0.004), respectively. At last follow-up, multivariable linear models demonstrated that a biopsy-proven malignancy (B = 2.630, 95% CI 0.024-5.236, P = 0.048) and AS strategy (B = 6.499, 95% CI 2.340-10.658, P = 0.002) were associated with worse PDSS in all patients, and in those who underwent a biopsy, respectively., Conclusions: Offering standardized psychological supportive care may be required for patients younger than 70 years on AS for SRM, especially for those with a biopsy-proven tumor., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: We describe the cardiovascular risk profile in a representative cohort of patients with prostate cancer treated with or without androgen deprivation therapy., Materials and Methods: We prospectively characterized in detail 2,492 consecutive men (mean age 68 years) with prostate cancer (newly diagnosed or with a plan to prescribe androgen deprivation therapy for the first time) from 16 Canadian sites. Cardiovascular risk was estimated by calculating Framingham risk scores., Results: Most men (92%) had new prostate cancer (intermediate risk 41%, high risk 50%). The highest level of education achieved was primary school in 12%. Most (58%) were current or former smokers, 22% had known cardiovascular disease, 16% diabetes, 45% hypertension, 31% body mass index 30 kg/m 2 or greater, 24% low levels of physical activity, mean handgrip strength was 37.3 kg and 69% had a Framingham risk score consistent with high cardiovascular risk. Participants in whom androgen deprivation therapy was planned had higher Framingham risk scores than those not intending to receive androgen deprivation therapy, and this risk was abolished after adjustment for confounders., Conclusions: Two-thirds of men with prostate cancer are at high cardiovascular risk. There is a positive association between a plan to use androgen deprivation therapy and baseline cardiovascular risk factors. However, this association is explained by confounding factors.

Introduction: Radical orchiectomy (RO) is the standard treatment for a testis cancer. Organ sparing surgery can be considered in the setting of a solitary functioning testis or bilateral tumors. It has also been suggested as an alternative to RO for small lesions. In this study we report our partial orchiectomy (PO) experience., Methods: We performed a retrospective review using our prospectively maintained database analyzing PO., Results: Between 1983 and 2018, 77 patients underwent PO. Mean age was 31.3 years (range 17-56). A lesion was palpable in 70 (90.9%) and median lesion size 14.1 mm (range 3-35 mm). Reasons for PO included ``small lesion" in 39 (50.6%); solitary functioning testis in 30 (39%); bilateral lesions in 6 (7.8%); or assumed benign lesion in 1 (1.3%). Median follow-up was 43.5 months (range 1-258). Lesion histology was benign in 25 (32.5%). A positive surgical margin was noted in 6 (7.8%) with none developing local or distant recurrence. Sixteen (20.8%) patients underwent salvage ipsilateral RO at a median of 3 months (range 0-46). Reasons for salvage RO included a radiologically detected lesion in 7, palpable lesion in 4, positive surgical margin in 3 and adverse pathology in 2 patients. Malignant histology was present in 12 (75%) of the salvage RO specimens. There were no reported Clavien-Dindo Grade 3 to 5 complications., Conclusion: Organ sparing surgery is a safe and feasible approach to small testis lesions. For the third with benign disease, and even those with malignant histology, a RO can be avoided in carefully selected patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The purpose of this article is to describe palliative care incorporation within the care of heart transplant patients. Palliative care is a holistic approach to care that includes symptom management and goal setting to improve patients' quality of life. Palliative care is designed to be used with patients who have chronic illness that impacts quality of life and should be incorporated early in the disease. All providers have a responsibility to be knowledgeable in palliative care approaches and to know when to refer a patient for specialty palliative care services. This article will describe palliative care, research study findings, and current professional guideline recommendations for patients. The article also describes challenges and barriers to the use of palliative care in heart transplant patients and strategies to address these challenges and barriers.

Introduction: Active surveillance (AS) is an accepted management strategy for low-risk prostate cancer (PCa), but its role in the management of favorable intermediate-risk PCa remains controversial. Most reports studying the role of AS for these men generally lack long-term followup and include small numbers of patients. Our objective was to report the outcomes of men diagnosed with Gleason grade groups (GGG) 2 and 3 PCa who were managed expectantly., Methods: Using administrative datasets and pathology reports, we identified all men who were diagnosed with GGG 2 and 3 PCa and managed expectantly between 2002 and 2011 in Ontario, Canada. Outcomes and associated factors were estimated using cumulative incidence function methods and multivariable Cox regression models, respectively., Results: We identified 926 men who were managed expectantly (AS [n=374] or watchful waiting [n=552]). The eight-year cancer-specific survival was 94% and 89% for the AS and watchful waiting cohorts, respectively. Among AS men, 266 (71%) received treatment after a followup of approximately eight years. Cumulative AS discontinuation rates at one and five years were 30.5% and 65.1%, respectively., Conclusions: Expectant management of GGG 2 and 3 PCa may be an option for certain men. Notably for AS patients, the cancer-specific mortality at eight years was 6%, and over 65% of men underwent treatment within five years. Further studies are required to evaluate which patients, based on disease-specific features and competing health risks, would benefit most from a conservative strategy.

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., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Objective: To compare a simultaneous vs sequential approach to residual post chemotherapy mass resections in metastatic testis cancer., Methods: A retrospective review was performed of patients who underwent retroperitoneal and thoracic/cervical resection of post chemotherapy residual masses between 2002 and 2018. Group 1: "Simultaneous" (Combined Retroperitoneal and Thoracic/Cervical resections on the same date); Group 2: "Sequential" (Retroperitoneal and Thoracic/Cervical resections at separate dates)., Results: During the study period, 35 simultaneous and 17 sequential resections were performed. The median age at surgery was 28 years (Range 16-61). The median follow-up from last surgical procedure was 62.7 months (Range 0.4-194). Histology revealed teratoma in 38 (73.1%) patients, necrosis in 8 (15.4%) and viable tumor in 6 (11.5%). Discordant pathology findings between thoracic/cervical and abdominal resections were noted in 16 (30.8%) patients. No differences were observed between the simultaneous vs sequential groups in median operating time (585 minutes vs 545 minutes, P = .64), blood loss (1300 vs 1300 mls, P = .42), or length of stay (9 vs 11 days, P = .14). There was no difference between the 5-year (65.7% vs 68.6%) relapse-free survival between the 2 groups (P = .84) or the 5-year (88.6% vs 100%) overall and disease-specific survival (P = .25)., Conclusion: Simultaneous resection of retroperitoneal and thoracic/cervical post chemotherapy metastases is a feasible in some patients. It requires multidisciplinary collaboration and a longer primary procedure., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The closure of Hahnemann University Hospital, which was announced on June 26, 2019, resulted in the most significant graduate medical education displacement in history, sending over 550 residents to new institutions within a month of the announcement. Over 2,000 physicians, nurses, and staff lost their jobs. While seemingly predictable in retrospect, the closure came as a cataclysmic event to all involved. In this Invited Commentary, a department chair reflects on the lessons learned from these unprecedented circumstances. These lessons cover areas that are not a typical concern for faculty who are focused on teaching their trainees, but are worthy of their attention. Corporate and organizational structure, leadership, and financing of the hospital were critical determining characteristics of the failure. The roles that the Accreditation Council for Graduate Medical Education and the Centers for Medicare and Medicaid Services played in this event were key stabilizers. However, examining their roles in this event offers opportunities to play a more active role in future events and alter how the next massive displacement unfolds, possibly preserving teaching programs. Highly competitive health systems should rethink noncollaborative strategies before allowing struggling institutions to succumb to market forces. Finally, a commitment by a hospital to the mission of academic medicine is a sacred trust with the faculty, trainees, and patients that it serves. It should not be undertaken by any enterprise that is not well resourced and equipped with the knowledge and expertise to meet this most serious of commitments.

Introduction: The management of advanced prostate cancer (PCa) continues to evolve with the emergence of new diagnostic and therapeutic strategies. As a result, there are multiple areas in this landscape with a lack of high-level evidence to guide practice. Consensus initiatives are an approach to establishing practice guidance in areas where evidence is unclear. We conducted a Canadian-based consensus forum to address key controversial areas in the management of advanced PCa., Methods: As part of a modified Delphi process, a core scientific group of PCa physicians (n=8) identified controversial areas for discussion and developed an initial set of questions, which were then reviewed and finalized with a larger group of 29 multidisciplinary PCa specialists. The main areas of focus were non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic castration-sensitive prostate cancer (mCSPC), metastatic castration-resistant prostate cancer (mCRPC), oligometastatic prostate cancer, genetic testing in prostate cancer, and imaging in advanced prostate cancer. The predetermined threshold for consensus was set at 74% (agreement from 20 of 27 participating physicians)., Results: Consensus participants included uro-oncologists (n=13), medical oncologists (n=10), and radiation oncologists (n=4). Of the 64 questions, consensus was reached in 30 questions (n=5 unanimously). Consensus was more common for questions related to biochemical recurrence, sequencing of therapies, and mCRPC., Conclusions: A Canadian consensus forum in PCa identified areas of agreement in nearly 50% of questions discussed. Areas of variability may represent opportunities for further research, education, and sharing of best practices. These findings reinforce the value of multidisciplinary consensus initiatives to optimize patient care.

Globally, groupers (Epinephelidae) that form fish spawning aggregations (FSAs) are highly vulnerable to overfishing and often require site-specific approaches to management. Over 5-years (2009-2013), we conducted underwater visual censuses (UVC) at a well-known spawning site at Njari Island, Gizo, Western Province, Solomon Islands, that supports aggregations of squaretail coralgrouper (Plectropomus areolatus), camouflage grouper (Epinephelus polyphekadion) and brown-marbled grouper (E. fuscoguttatus). Findings show that while there were species-specific variations in the duration and timing of the spawning season, aggregation densities peaked from March to June, representing the main spawning season for all three species. For P. areolatus, gonad analysis from samples taken from 2008 to 2011 confirmed reproductive activity in support of density trends observed through UVC. Over the 5-year UVC monitoring period, FSA densities declined for P. areolatus and E. polyphekadion. Conversely, following the first year of monitoring, E. fuscoguttatus densities increased. These inter-specific differences may reflect variable responses to fishing as shown elsewhere, or for example, differences in recruitment success. In response to known declines in FSAs of these species, in 2018 the Solomon Islands government placed a nationwide ban on these species' harvest and sale between October and January. As this study shows, this ban does not encompass the peak aggregation period at Njari and will offer limited protection to other FSAs of these species that are known to vary in reproductive seasonality across the Solomon Islands. A more biologically meaningful and practical management strategy would be to implement a nationwide ban on the harvest and sale of these groupers each month between full and new moons when these FSAs form consistently throughout the country. Since effective management of FSAs typically requires a combined approach, spatial management that protects both spawning sites and reproductive migratory corridors is warranted., Competing Interests: No authors have competing interests.

Background: Few data exist on the relationship of cisplatin-related adverse health outcomes (AHOs) with disability, unemployment, and self-reported health (SRH) among testicular cancer survivors (TCS)., Methods: A total of 1815 TCS at least 1 year postchemotherapy underwent clinical examination and completed questionnaires. Treatment data were abstracted from medical records. A cumulative burden of morbidity score (CBM Pt ) encompassed the number and severity of platinum-related AHOs (peripheral sensory neuropathy [PSN], hearing loss, tinnitus, renal disease). Multivariable regression assessed the association of AHOs and CBM Pt with employment status and SRH, adjusting for sociodemographic and clinical characteristics. Unemployment was compared with a male normative population of similar age, race, and ethnicity., Results: Almost 1 in 10 TCS was out of work (2.4%, disability leave; 6.8%, unemployed) at a median age of 37 years (median follow-up = 4 years). PSN (odds ratio [OR] = 2.89, 95% confidence interval [CI] = 1.01 to 8.26, grade 3 vs 0, P  = .048), renal dysfunction defined by estimated glomerular filtration rate (OR = 12.1, 95% CI = 2.06 to 70.8, grade 2 vs 0, P  = .01), pain (OR = 10.6, 95% CI = 4.40 to 25.40, grade 2 or 3 vs 0, P  < .001), and CBM Pt (OR = 1.46, 95% CI = 1.03 to 2.08, P  = .03) were associated with disability leave; pain strongly correlated with PSN ( r 2 = 0.40, P  < .001). Statistically significantly higher percentages of TCS were unemployed vs population norms (age-adjusted OR = 2.67, 95% CI = 2.49 to 3.02, P  < .001). PSN (OR = 2.44, 95% CI = 1.28 to 4.62, grade 3 vs 0, P  = .006), patient-reported hearing loss (OR = 1.82, 95% CI = 1.04 to 3.17, grade 2 or 3 vs 0, P  = .04), and pain (OR = 3.75, 95% CI = 2.06 to 6.81, grade 2 or 3 vs 0, P  < .001) were associated with unemployment. Increasing severity of most cisplatin-related AHOs and pain were associated with statistically significantly worse SRH., Conclusions: Our findings have important implications regarding treatment-associated productivity losses and socioeconomic costs in this young population. Survivorship care strategies should include inquiries about disability and unemployment status, with efforts made to assist affected TCS in returning to the workforce., (© The Author(s) 2020. Published by Oxford University Press.)

Background: Dual defibrillation (DD) is a technique where two external defibrillators are applied with two different pad configurations and discharged to treat refractory ventricular fibrillation (RVF). Although commonly called dual sequential defibrillation (DSD), if the delivered electrical pulses overlap with no pulse interval, the shocks are actually dual simultaneous defibrillation (DSiD). Manual DD technique is not standardized and the effect that the method of activation has on the delivered pulse interval has never been studied. Objectives: This study measured the timing of four methods of DD and the resulting inter-shock intervals, frequency with which they were either DSiD or DSD, and frequency which the true DSDs delivered any previously reported optimum pulse interval. Methods: This was a single-blinded prospective evaluation of a convenience sample of volunteer physicians, nurses, and paramedics each performing DD in our simulation center on two types of defibrillators using four techniques: single operator-simultaneous with 2 hands (SOSI), two operators-simultaneous (TOSI), single operator-sequential with 1 hand (SOSE1), and single operator-sequential with 2 hands (SOSE2). Results: The four DD methods generated a variable set of pulse intervals depending on the technique and defibrillator employed. The pulse intervals ranged from 0 msec (i.e., overlapping waveforms or DSiD) to 1800 msec. Of all DD attempts, 85.9% met the definition of DSD, 14.1% were DSiD, and 49.4% delivered any one of the optimum pulse intervals previously described in the literature. SOSI and TOSI techniques resulted in DSD between 47.2 and 87.6% of the time, depending on the technique and defibrillator. Shocks delivered sequentially on purpose (SOSE2 and SOSE1) were always DSD but with widely variable pulse intervals. SOSI resulted in the shortest pulse intervals, SOSE1 resulted in the longest, and TOSI and SOSE2 were the least skewed. Conclusion: DD using the various methods currently employed produces a highly variable set of pulse intervals even within a single method. It is difficult to reach a conclusion about the efficacy of DD unless the delivered pulse interval is measured or the method of activation reproducibly produces a precise pulse interval.

Purpose of Review: Approximately 30% of clinical stage 1 (CS1) nonseminomatous germ cell tumours (NSGCT) and 15-20% of CS1 seminoma relapse without adjuvant treatment. Despite this, the 5-year survival for CS1 is 99%. The purpose of this review is to assess if active surveillance should be standard for all patients with CS1 testis cancer independent of risk factors., Recent Findings: Recent data from Princess Margaret Cancer Centre suggest a nonrisk-adapted surveillance approach avoids treatment in ∼70% of patients. Most relapse early at a median time of 7.4 months. The majority of relapses are confined to the retroperitoneum (66%) and only one modality of treatment is required: chemotherapy only in 61% and RPLND only in 73%., Summary: Surveillance is the preferred option and a safe proven strategy for the management of CS1 disease independent of risk factors. The prognosis for CS1 disease is excellent and the decision to offer surveillance or adjuvant treatment needs to highlight the treatment-related morbidity in an otherwise fit and healthy young man.

Introduction: Prostate cancer poses a significant lifetime risk to Canadian men. Treatment for metastatic prostatic cancer (mPCa) is an area of ongoing research with a lack of up-to-date clinical guidance. The multidisciplinary Canadian Genitourinary Research Consortium (GURC) determined that additional guidance focusing on management of mPCa was warranted., Methods: The most up-to-date guidelines, consensus statements, and emerging phase 3 trials were identified and used to inform development of algorithms by a multidisciplinary genitourinary oncology panel outlining recommendations for the management of mPCa., Results: A single pan-Canadian guideline and five national and international guidelines or consensus statements published since 2015 were identified, along with two new phase 3 trials and one additional randomized comparison. Iterative GURC discussions led to the development of two mPCa algorithms: the first addressing management of newly diagnosed metastatic castration-sensitive prostate cancer (mCSPC) patients and the second addressing treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). For newly diagnosed mCSPC patients with high-volume/high-risk disease, either docetaxel or abiraterone acetate and prednisone (AAP) added to androgen-deprivation therapy (ADT) is recommended. The addition of radiotherapy to ADT is suggested for those with low-volume disease and/or AAP to ADT for low-volume or low-risk disease. For first-line mCRPC, androgen receptor-axis-targeted (ARAT) therapy is recommended for most patients, while sequencing with docetaxel, radium-223, ARAT therapy, and/or cabazitaxel is recommended for later lines of therapy., Conclusions: Two treatment algorithms were developed for the management of mPC and can be used by multidisciplinary specialist teams to guide treatment.

Liquid biopsy-based biomarkers, such as microRNAs, represent valuable tools for patient management, but often do not make it to integration in the clinic. We aim to explore issues impeding this transition, in the setting of germ cell tumors, for which novel biomarkers are needed. We describe a model for identifying and validating clinically relevant microRNAs for germ cell tumor patients, using both in vitro, in vivo (mouse model) and patient-derived data. Initial wide screening of candidate microRNAs is performed, followed by targeted profiling of potentially relevant biomarkers. We demonstrate the relevance of appropriate (negative) controls, experimental conditions (proliferation), and issues related to sample origin (serum, plasma, cerebral spinal fluid) and pre-analytical variables (hemolysis, contaminants, temperature), all of which could interfere with liquid biopsy-based studies and their conclusions. Finally, we show the value of our identification model in a specific scenario, contradicting the presumed role of miR-375 as marker of teratoma histology in liquid biopsy setting. Our findings indicate other putative microRNAs (miR-885-5p, miR-448 and miR-197-3p) fulfilling this clinical need. The identification model is informative to identify the best candidate microRNAs to pursue in a clinical setting.

Introduction: Current prostate cancer (PCa) guidelines primarily focus on localized or metastatic PCa. A multidisciplinary genitourinary oncology panel determined that additional guidance focusing on monitoring and management of biochemical recurrence (BCR) following radical therapy and non-metastatic castration-resistant prostate cancer (nmCRPC) was warranted., Methods: The most up-to-date national and international guidelines, consensus statements, and emerging phase 3 trials were identified and used to inform development of algorithms by a multidisciplinary genitourinary oncology panel outlining optimal monitoring and treatment for patients with non-metastatic PCa., Results: A total of eight major national and international guidelines/consensus statements published since 2015 and three phase 3 trials were identified. Working group discussions among the multidisciplinary genitourinary oncology panel led to the development of two algorithms: the first addressing management of patients with BCR following radical therapy (post-BCR), and the second addressing management of nmCRPC. The post-BCR algorithm suggests consideration of early salvage treatment in select patients and provides guidance regarding observation vs. intermittent or continuous androgen-deprivation therapy (ADT). The nmCRPC algorithm suggests continued ADT and monitoring for all patients, with consideration of treatment with apalutamide or enzalutamide for patients with high-risk disease (prostate-specific antigen [PSA] doubling time of ≤ 10 months)., Conclusions: Two treatment algorithms have been developed to guide the management of non-metastatic PCa and should be considered in the context of local guidelines and practice patterns.

We studied the dosimetry of single-isocenter treatment plans generated to treat a solitary intracranial lesion using linac-based stereotactic radiosurgery (SRS). A common metric for evaluating SRS plan quality is the volume of normal brain tissue irradiated by a dose of at least 12 Gy (V12), which is important because multiple studies have shown a strong correlation between V12 and incidence of radiation necrosis. Unrealistic expectations for values of V12 can lead to wasted planning time. We present a model that estimates V12 without having to construct a full treatment plan. This model was derived by retrospectively analyzing 50 SRS treatment plans, each clinically approved for delivery using circular collimator cone arc therapy (CAT). Each case was re-planned for delivery via dynamic conformal arc therapy (DCAT), and then scaling arguments were used to extend dosimetric data to account for different prescription dose (PD) values (15, 18, 21, or 24 Gy). We determined a phenomenological expression for the total volume receiving at least 12 Gy (TV12) as a function of both planning target volume (PTV) and PD: T V 12 / 1 c c = n ∗ P D / 1 G y + d ∗ P T V / 1 c c a ∗ P D / 1 G y c , where a , c , n , d are fit parameters, and a separate set of values is determined for each plan type. In addition, we generated a sequence of plots to clarify how the relationship between conformity index (CI) and TV12 depends on plan type (CAT vs DCAT), PTV, and PD. These results can be used to suggest realistic plan parameters and planning goals before the start of treatment planning. In the absence of access to more sophisticated pre-planning tools, this model can be locally generated and implemented at relatively low cost with respect to time, money, and expertise., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: Our objective was to evaluate operating characteristics, particularly specificity and positive predictive value (PPV), by mapping plasma miR371 expression to actual clinical events in patients with a history of germ cell tumor., Patients and Methods: One hundred eleven male patients with a history of or newly diagnosed germ cell tumors were evaluable. Biospecimens obtained before confirmed clinical events were analyzed for miR371 expression with blinding of providers and laboratory personnel to analytic results or clinical status, respectively. Cases (patients with clinically confirmed active germ cell malignancy [aGCM]) and controls (patients with no clinically confirmed aGCM) were assigned over the course of the management. Patients were assigned risk status (high, low, or moderate) based on the composite clinical picture at time points in management., Results: Considering all cases and controls and results of prospectively obtained biosamples analyzed for miR371 expression, 46 (35%) of 132 samples had clinically confirmed aGCM over the course of management; 44 (96%) of these 46 patients had plasma miR371 expression (true positives) with no false positives. Two (4%) of 46 patients had no miRNA expression despite pathologic confirmation of aGCM (false negatives). Plasma miR371 expression in confirmed aGCM had a specificity, sensitivity, positive predictive value, and negative predictive value of 100%, 96%, 100%, and 98%, respectively. Interpretation of sensitivity and negative predictive value is limited by modest follow-up. Specificity and sensitivity were 100% and 98%, 100% and 92%, and 100% and 97% in the low-, moderate-, and high-risk groups, respectively, with a median follow-up time of 15 months., Conclusion: Plasma miR371 expression predicts aGCM with high specificity and positive predictive value. Although other operating characteristics of miR371 await longer follow-up for more complete definition, the findings of a highly specific liquid biopsy strongly support moving forward with large-scale, real-world clinical trials to further define full operating characteristics and to identify clinical utility and areas of patient benefit.

Background: The growing number of homeless persons in the United States demonstrates greater morbidity and mortality than the population as a whole. Homeless persons are often without a regular source of primary care. Homeless persons use emergency departments and are hospitalized at higher rates than nonhomeless persons. In 2010, the enactment of the Affordable Care Act expanded access to primary care services. Nurse practitioners were at the forefront of its subsequent implementation., Purpose: The purpose of this qualitative study was to explore the factors that influence establishing and maintaining a regular source of primary care among homeless persons., Methodological Orientation: In 2017, semistructured interviews were conducted in a federally qualified health center that serves predominately homeless persons., Sample: A purposive convenience sample included adult health center users (N = 20). The majority of participants were insured (90%), African American (70%), and male (65%)., Conclusions: Thematic analysis revealed five facilitators: sense of community, mutual patient-provider respect, financial assurance, integrated health services, and patient care teams. To establish and maintain use of a regular primary care source, homeless persons desire to experience a sense of community, feel respected by their provider/staff, and have certainty that costs will not exceed their capacity to pay. Integrated care models that leverage a multidisciplinary team approach support the use of a regular primary care source., Implications for Practice: Actualizing achievable strategies that promote the consistent use of a regular primary care source can reduce use of avoidable emergency and hospital-based services, thereby improving health outcomes among homeless persons., Competing Interests: Competing interests: The authors report no conflicts of interest., (Copyright © 2019 American Association of Nurse Practitioners.)

Objectives: To present long-term oncological outcomes of patients with paratesticular sarcoma treated by a multidisciplinary team., Patients and Methods: Patients managed at the Princess Margaret Cancer Centre, between 1990 and 2012, were analysed. A sarcoma expert performed central pathology review. Kaplan-Meier graphs compared local recurrence (LR), metastasis, and overall survival (OS) of patients treated with hemiscrotectomy vs those who did not. Univariable Cox proportional hazards analysis was performed to delineate predictors of LR, metastasis, and OS., Results: Overall, 51 patients with a median (interquartile range) follow-up of 132 (51.6-226.8) months were analysed. At presentation, 92.2% (47 patients) had localised disease. Only five patients (9.8%) had undergone initially planned hemiscrotectomy. Completion and salvage hemiscrotectomy was performed in 25 (54.3%) and seven (15.2%) patients, respectively. Recurrence and metastasis occurred in 12 (25.5%) and 10 patients (19.6%), respectively. At the last follow-up, 21.6% (11 patients) had died, with eight dying from their disease. Kaplan-Meyer graphs demonstrated that hemiscrotectomy improved LR (median not reached vs 62.4 months, log-rank P = 0.008) and OS (median not reached vs 168 months, log-rank P = 0.081). Univariable analysis found hemiscrotectomy to be associated with a lower LR rate (hazard ratio [HR] 0.21, P = 0.02), whilst positive margins at initial surgery were associated with increased LR (HR 4.81, P = 0.047). No metastasis predictors were found, but age (HR 1.04, 95% confidence interval [CI] 1.0-1.08; P = 0.02) and non-localised disease at presentation (HR5.17, 95% CI 1.33-20.06; P = 0.017) were associated with worse OS., Conclusion: Paratesticular sarcoma is a rare tumour, predominantly manifesting as localised disease. Most patients receive an initial suboptimal oncological surgery. Improved long-term outcomes are demonstrated following early hemiscrotectomy., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels., Experimental Design: Eligible TCS given 300 or 400 (±15) mg/m 2 cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured. Associations between serum platinum and various risk factors and toxicities were assessed after fitting a biexponential model adjusted for follow-up time and cumulative cisplatin dose. A genome-wide association study (GWAS) was performed using the serum platinum residuals of the dose and time-adjusted model., Results: Serum platinum levels exceeded the reference range for approximately 31 years, with a strong inverse relationship with creatinine clearance at follow-up (age-adjusted P = 2.13 × 10 -3 ). We observed a significant, positive association between residual platinum values and luteinizing hormone (age-adjusted P = 6.58 × 10 -3 ). Patients with high residual platinum levels experienced greater Raynaud phenomenon than those with medium or low levels (age-adjusted OR high/low = 1.46; P = 0.04), as well as a higher likelihood of developing tinnitus (age-adjusted OR high/low = 1.68, P = 0.07). GWAS identified one single-nucleotide polymorphism (SNP) meeting genome-wide significance, rs1377817 ( P = 4.6 × 10 -8 , a SNP intronic to MYH14 )., Conclusions: This study indicates that residual platinum values are correlated with several cisplatin-related toxicities. One genetic variant is associated with these levels., (©2019 American Association for Cancer Research.)

Purpose of Review: Traditionally, local treatment was reserved for palliative control of symptoms in men with metastatic prostate cancer. In the past few years there have been many advances in the systemic options available. The aim of this review is to explore the evidence in support of treating the primary tumor despite the presence of metastatic disease., Recent Findings: There is a wealth of retrospective studies demonstrating advantages of local treatment [radical prostatectomy or radiation therapy (RT)] in metastatic disease. As these studies are prone to bias, treatment of the primary in the metastatic setting has not been adopted. However, two recent prospective randomized trials (HORRAD and STAMPEDE) have addressed the role of RT to the prostate in metastatic disease. The STAMPEDE sub-group analysis of low-volume metastatic disease demonstrated a survival advantage in favor of the RT arm (hazard ratio 0.68; 95% CI 0.52-0.90). The HORRAD trial showed a similar but nonsignificant trend towards RT (hazard ratio 0.68; 95% CI 0.42-1.10). As a result, the 2019 European Association of Urology and National Comprehensive Cancer Network guidelines now include RT to the prostate as an option in the setting of low-volume metastatic disease., Summary: Although systemic treatment remains standard of care for men with metastatic prostate cancer, there is recent compelling evidence from two prospective randomized trials supporting treatment of the prostate in oligometastatic disease.

At Princess Margaret, we recommend active surveillance for all patients with clinical stage I nonseminomatous germ cell tumor. Here we refute common arguments against surveillance and urge clinicians to engage in a shared decision-making process that goes beyond merely citing relapse rates for the different options., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Diabetes has been associated with worse survival outcomes in various malignancies; however, there are conflicting data in kidney cancer. Determining whether diabetes is associated with survival in kidney cancer may help guide treatment in a comorbid patient population., Methods: We used the Canadian Kidney Cancer information system database to identify patients undergoing partial or radical nephrectomy between 1989 and 2017 for localized renal cell carcinoma at 16 institutions across Canada. We derived inverse probability of treatment weights (IPTW) from a propensity score model based on various clinical, surgical, and pathological characteristics. We used Cox proportional hazard models to evaluate the association between diabetes and cancer-specific and overall survival, in the sample weighted by the IPTW., Results: 4828 patients met inclusion criteria, of whom 948 (19.6%) were diabetic. Median follow-up in those without death was 26.6 months (interquartile range 9.7-53.8). Among the entire cohort, 901 deaths were from any cause, and 299 deaths from kidney cancer. Before propensity score methods, diabetics were older, more likely to have comorbidities and clear cell histopathology. After propensity score adjustment, all characteristics were balanced between groups (standardized difference <0.10). IPTW-adjusted Cox proportional hazard models demonstrated no significant association between diabetes and cancer-specific (hazard ratio 1.13, 95% confidence interval 0.78-1.62), or overall survival (hazard ratio 1.14, 95% confidence interval 0.94-1.38)., Conclusions: Our multi-centre study found that diabetes and nondiabetics have similar survival following nephrectomy for kidney cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Upper tract urothelial carcinoma (UTUC) accounts for &lt;5% of all urothelial cancers. We aimed to ascertain the clinical differences between UTUC tumours presenting de novo (DnUTUC) and those presenting secondary (SUTUC) following a bladder cancer diagnosis., Methods: Our institutional database was queried for all UTUC patients who were surgically treated with radical nephroureterectomy or ureterectomy between 2003 and 2017. Bladder recurrence and cancer-specific mortality were compared. To reduce the possible bias due to confounding variables obtained from a simple comparison of outcomes, DnUTUC patients were matched (for age, gender, tumour location, type of surgery, grade, TNM staging, presence of carcinoma in situ, and lymphovascular invasion) with propensity score to SUTUC patients. Bladder recurrence and cancer-specific mortality were assessed with Cox proportional hazards model., Results: A total of 117 UTUC patients were identified: 80 with DnUTUC (68.4%) and 37 with SUTUC (31.6%). A greater proportion of males with SUTUC was demonstrated (89.2% vs. 68.8; p=0.02). In both groups, 67.5% of patients had high-grade disease, but SUTUC demonstrated a higher carcinoma in situ rate (43.2% vs. 25%; p=0.047). Univariate analysis demonstrated that the five-year bladder recurrence rate was trending to be higher in SUTUC (65.3% vs. 20.5%; p=0.099). In the Cox model, however, it was associated with increased bladder recurrence (hazard ratio [HR] 3.69; 95% confidence interval [CI] 1.68-8.09; p=0.001). Although univariate analysis demonstrated that SUTUC patients were more likely to die of their disease (30.6% vs. 9%; p=0.009), the multivariable Cox model did not demonstrate this association. The limitations of this study include its retrospective, single-centre design and relatively small cohort of patients., Conclusions: In this hypothesis-generating study, some evidence suggests that further research is needed to delineate differences between SUTUC and DnUTUC.

Retroperitoneal lymph node dissection (RPLND) is complex; however, recent advances in technology have allowed adoption of the robotic platform for highly select cases. Initial case series have shown improved cosmesis, less blood loss, and decreased length of stay compared with open RPLND. Our preference for performing robotic RPLND is via a transperitoneal approach with the patient in the supine position, thus facilitating a bilateral template dissection identical to that used in all our open procedures. Robotic RPLND should mimic the open approach with regard to oncologic principles and should only be performed by clinicians well versed in open RPLND., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Active surveillance (AS) for testicular nonseminomatous germ cell tumors (NSGCT) is widely used. Although there is no consensus for optimal treatment at relapse on surveillance, globally patients typically receive chemotherapy. We describe treatment of relapses in our non-risk-adapted NSGCT AS cohort and highlight selective use of primary retroperitoneal lymph node dissection (RPLND)., Methods: From December 1980 to December 2015, 580 patients with clinical stage I NSGCT were treated with AS, and 162 subsequently relapsed. First-line treatment was based on relapse site and extent. Logistic regression was used to explore factors associated with need for multimodal therapy on AS relapse., Results: Median time to relapse was 7.4 months. The majority of relapses were confined to the retroperitoneum (66%). After relapse, first-line treatment was chemotherapy for 95 (58.6%) and RPLND for 62 (38.3%), and five patients (3.1%) underwent other therapy. In 103 (65.6%), only one modality of treatment was required: chemotherapy only in 58 of 95 (61%) and RPLND only in 45 of 62 (73%). Factors associated with multimodal relapse therapy were larger node size (odds ratio, 2.68; P = .045) in patients undergoing chemotherapy and elevated tumor markers (odds ratio, 6.05; P = .008) in patients undergoing RPLND. When RPLND was performed with normal markers, 82% required no further treatment. Second relapse occurred in 30 of 162 patients (18.5%). With median follow-up of 7.6 years, there were five deaths (3.1% of AS relapses, but 0.8% of whole AS cohort) from NSGCT or treatment complications., Conclusion: The retroperitoneum is the most common site of relapse in clinical stage I NSGCT on AS. Most are cured by single-modality treatment. RPLND should be considered for relapsed patients, especially those with disease limited to the retroperitoneum and normal markers, as an option to avoid chemotherapy.

Introduction: Active surveillance (AS) is standard of care in low-risk prostate cancer (PCa). This study describes a novel total cancer location (TCLo) density metric and aims to determine its performance in predicting clinical progression (CP) and grade progression (GP)., Methods: This was a retrospective study of patients on AS after confirmatory biopsy (CBx). We excluded patients with Gleason ≥7 at CBx and <2 years followup. TCLo was the number of locations with positive cores at diagnosis (DBx) and CBx. TCLo density was TCLo/prostate volume (PV). CP was progression to any active treatment while GP occurred if Gleason ≥7 was identified on repeat biopsy or surgical pathology. Independent predictors of time to CP or GP were estimated with Cox regression. Kaplan-Meier analysis compared progression-free survival (PFS) curves between TCLo density groups. Test characteristics of TCLo density were explored with receiver operating characteristic (ROC) curves., Results: We included 181 patients who had CBx from 2012-2015 and met inclusion criteria. The mean age of patients was 62.58 years (standard deviation [SD] 7.13) and median followup was 60.9 months (interquartile range [IQR] 23.4). A high TCLo density score (>0.05) was independently associated with time to CP (hazard ratio [HR] 4.70; 95% confidence interval [CI] 2.62-8.42; p<0.001) and GP (HR 3.85; 95% CI 1.91-7.73; p<0.001). ROC curves showed TCLo density has greater area under the curve than number of positive cores at CBx in predicting progression., Conclusions: TCLo density is able to stratify patients on AS for risk of CP and GP. With further validation, it could be added to the decision-making algorithm in AS for low-risk localized PCa.