Gregory Joice

A Prospective, Comparative Study of Quality of Life among Patients with Small Renal Masses Choosing Active Surveillance and Primary Intervention

PURPOSE To our knowledge quality of life has not been evaluated in rigorous fashion in patients undergoing active surveillance for small renal masses. The prospective, multi-institutional DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry was opened on January 1, 2009, enrolling patients with cT1a (4.0 cm or less) small renal masses who elected primary intervention or active surveillance. MATERIALS AND METHODS Patients were enrolled following a choice of active surveillance or primary intervention. The active surveillance protocol includes imaging every 4 to 6 months for 2 years and every 6 to 12 months thereafter. The SF12® quality of life questionnaire was completed at study enrollment, at 6 and 12 months, and annually thereafter. MCS (Mental Component Summary), PCS (Physical Component Summary) and overall score were evaluated among the groups and with time using ANOVA and linear regression mixed modeling. RESULTS At 82 months among 3 institutions 539 patients were enrolled with a mean ± SD followup of 1.8 ± 1.7 years. Of the patients 254 were on active surveillance, 285 were on primary intervention and 21 were on active surveillance but crossed over to delayed intervention. A total of 1,497 questionnaires were completed. Total and PCS quality of life scores were better for primary intervention at enrollment through 5 years. There were generally no differences in MCS scores among the groups and there was a trend of improving scores with time. CONCLUSIONS In a prospective registry of patients undergoing active surveillance or primary intervention for small renal masses those undergoing primary intervention had higher quality of life scores at baseline. This was due to a perceived benefit in the physical health domain, which persisted throughout followup. Mental health, which includes the domains of depression and anxiety, was not adversely affected while on active surveillance, and it improved with time after selecting a management strategy.

Three-dimensional organoid culture reveals involvement of Wnt/β-catenin pathway in proliferation of bladder cancer cells

There has been increasing awareness of the importance of three-dimensional culture of cancer cells. Tumor cells growing as multicellular spheroids in three-dimensional culture, alternatively called organoids, are widely believed to more closely mimic solid tumors in situ. Previous studies concluded that the Wnt/β-catenin pathway is required for regeneration of the normal urothelium after injury and that β-catenin is upregulated in human bladder cancers, but no clear evidence has been advanced to support the idea that the Wnt/β-catenin pathway is directly involved in deregulated proliferation and the other malignant characteristics of bladder cancer cells. Here we report that the Wnt/β-catenin pathway activator, CHIR99021, promoted proliferation of established human bladder cancer cell lines when they were grown in organoid culture but not when they were grown in conventional adherent cultures. CHIR99021 activated Wnt/β-catenin pathway in bladder cancer cell lines in organoid culture. CHIR99021 also stimulated proliferation and the Wnt/b-catenin pathway in primary human bladder cancer organoids. RNAi-mediated knockdown of β-catenin blocked growth of organoids. The effects of CHIR99021 were associated with decreased expression of the urothelial terminal differentiation marker, cytokeratin 20. Our data suggest that the Wnt/β-catenin pathway is required for the proliferation of bladder cancer cells in three-dimensional organoid culture and provide a concrete example of why organoid culture is important for cancer research.

Oligometastatic prostate cancer: Shaping the definition with molecular imaging and an improved understanding of tumor biology

Purpose of review The aim of this review is to discuss how novel imaging modalities and molecular markers are shaping the definition of oligometastatic prostate cancer. Recent findings To effectively classify a patient as having oligometastatic prostate cancer, diagnostic tests must be sensitive enough to detect subtle sites of metastatic disease. Conventional imaging modalities can readily detect widespread polymetastatic disease but do not have the sensitivity necessary to reliably classify patients as oligometastatic. Molecular imaging using both metabolic- and molecularly-targeted radiotracers has demonstrated great promise in aiding in our ability to define the oligometastatic state. Perhaps the most promising data to date have been generated with radiotracers targeting prostate-specific membrane antigen. In addition, early studies are beginning to define biologic markers in the oligometastatic state that may be indicative of disease with minimal metastatic potential. Summary Recent developments in molecular imaging have allowed for improved detection of metastatic prostate cancer allowing for more accurate staging of patients with oligometastatic disease. Future development of biologic markers may assist in defining the oligometastatic state and determining prognosis.

Nonsurgical Interventions for Peyronie's Disease: Update as of 2016

Peyronies disease (PD) is a debilitating condition of the penis that leads to significant pain, erectile dysfunction, and emotional distress in men. PD is likely underreported due to lack of knowledge of the disease and the absence of well-established available treatments. Surgical treatment can lead to sustained improvements, but is often associated with penile shortening and places the patient at risk for perioperative morbidity. Nonsurgical management has been studied for several years as an alternative to surgery for men with PD. Currently, much of the data on nonsurgical management is conflicting, with only one treatment that has been recently approved by the US Food and Drug Administration. Significant effort has been devoted to advancing non-surgical treatments for PD that can be implemented outside of the operating room. This review aims to describe the research behind current nonsurgical therapies for PD and to highlight the recent advances that have been made within the last three years.

Incidence of T3a up-staging and survival after partial nephrectomy: Size-stratified rates and implications for prognosis

BACKGROUND The use of partial nephrectomy (PN) to treat renal cell carcinoma has grown to include larger, more complex tumors. Such tumors are more likely to be up-staged to pT3a and generate controversy regarding the oncologic safety of PN. We aimed to estimate the proportion of patients up-staged to T3a disease after PN, stratified by clinical stage, and characterize their survival. METHODS From 1998 to 2013, pT1-pT3aN0M0 kidney cancer patients undergoing PN or radical nephrectomy (RN) were identified from the Surveillance Epidemiology and End Results registries. Cox proportional hazards models compared cancer-specific (CSS) and overall survival (OS) for PN patients with pT1a, pT1b, and pT2 disease to stratified, up-staged pT3a patients undergoing PN. Also, we compared PN patients with up-staged pT3a disease to RN patients with pT3a disease. RESULTS From the 28,854 patients undergoing PN, the estimated proportion up-staged to pT3a was 4.2%, 9.5%, and 19.5% for cT1a, cT1b, and cT2, respectively. OS was worse for tumors up-staged from cT1a to pT3a, but not for cT1b or cT2 tumors. Up-staged pT3a tumors across all stage strata demonstrated worse CSS, with worse survival for larger tumors. Analysis revealed no difference in OS or CSS for up-staged pT3a PN patients compared to pT3a RN patients. CONCLUSIONS A greater proportion of patients experience T3a up-staging after PN with increasing initial T stage. Up-staged pT3a patients have worse CSS across all clinical tumor stages after PN. However, our results do not demonstrate that patients up-staged after PN have compromised oncologic outcomes compared to all-comers with pT3a disease receiving RN.

Radiotherapy for stage I and II testicular seminomas: Secondary malignancies and survival

INTRODUCTION Testicular seminoma affects relatively young men with excellent survival outcomes. There has been increasing concern that radiotherapy (RT) leads to secondary malignant neoplasms (SMNs) and subsequent mortality. We evaluated the effect of RT on incidence of SMNs and quantified cancer-related mortality and other causes of death for patients with stage I and II testicular seminoma. MATERIAL AND METHODS A national sample of men (1988-2013) diagnosed with stage IA/IB/IS/IIA/IIB/IIC testicular seminomas from Surveillance, Epidemiology, and End Results were evaluated. Use of RT over time and survival curves (5/10/15-year) was stratified by stage. Log-binomial regression determined relative risk of developing SMNs. Incidence rate ratios (IRR) and age-adjusted Cox proportional hazards models compared overall, cancer-specific survival (CSS), and other cancer-specific survival. Competing-risks regression generated cumulative incidence functions. Prevalence ratios explored excess deaths owing to specific causes. RESULTS A total of 16,463 men were included with 9,126 (55.4%) undergoing RT with markedly decreased use for stage I seminoma in recent years (<20%) and ~50% for stage IIA. RT increased risk of SMNs (relative risk = 1.84 [95% CI: 1.61-2.10, P<0.01]). Survival rates were excellent (15-year CSS for stage I [≥99%], stage IIA [98.1%], stage IIB-C [96%-97%]). RT was associated with improved CSS for stage IB and IIA, but demonstrated less benefit for stage IA (IRR = 0.63 [95% CI: 0.35-1.14, P = 0.10]) with worse other cancer-specific survival (IRR = 1.80 [95% CI: 0.97-3.59, P = 0.05]). Gastrointestinal, respiratory, urinary, and hematologic malignances accounted for 84% of SMN deaths. CONCLUSIONS RT offers excellent CSS for men with stage I/II seminoma and an increased risk of SMN later in life. Future studies should better evaluate risk-stratification for stage IB patients.

Sickle Cell Disease in Priapism: Disparity in Care?

OBJECTIVE To determine the effect of sickle cell disease (SCD) on hospital resource use among patients admitted for priapism. MATERIALS AND METHODS Using the Nationwide Inpatient Sample, a weighted sample of 12,547 patients was selected with a primary diagnosis of priapism from 2002 to 2011. Baseline differences for patient demographics and hospital characteristics were compared between SCD and non-SCD patients. Multivariate analysis was performed to identify the effect of SCD on length of stay, use of penile operations, blood transfusion, and cost. RESULTS The proportion of SCD patients was 21.5%. SCD patients were younger, more often black, more likely to have Medicaid insurance, and treated more frequently in Southern urban teaching hospitals. SCD was a significant predictor of having a blood transfusion (odds ratio [OR], 16.3; P <.001), and an elongated length of stay (OR, 1.42; P <.001). SCD was associated with less penile operations (OR, 0.40; P <.001). When SCD patients did have an operation, it was performed later in the admission (mean, 0.87 vs 0.47 days; P <.001). SCD was not a significant predictor of increased cost (OR, 1.02; P = .869). CONCLUSION SCD patients represent a demographically distinct subgroup of priapism patients with different patterns of resource use manifested by longer hospital stays and more blood transfusions. Moreover, despite evidence that immediate treatment of priapism results in improved erectile function outcomes, SCD patients had less surgical procedures for alleviation of acute priapism events.

Initial Experience Performing In-office Ultrasound-guided Transperineal Prostate Biopsy Under Local Anesthesia Using the PrecisionPoint Transperineal Access System

OBJECTIVE To describe our procedural technique and initial outcomes performing in-office transperineal prostate biopsies using the PrecisionPoint Transperineal Access System (Perineologic, Cumberland, MD). PATIENTS AND METHODS Following institutional review board approval, we retrospectively reviewed the records of men who underwent an in-office transperineal prostate biopsy using the PrecisionPoint device. Records were reviewed for baseline characteristics, biopsy results, and postbiopsy complications. RESULTS Between January 4, 2017 and August 23, 2017, 43 men underwent an in-office transperineal prostate biopsy using the PrecisionPoint Transperineal Access System. Patients had a median serum prostate specific antigen level of 6.1 ng/mL (range 0.8-32.9). Of the 43 biopsies, 12 (27.9%) were performed for active surveillance of low-risk prostate cancer and 31 (72.1%) were performed for cancer screening. Overall, 21 (48.8%) men were found to have prostate cancer. Among those on active surveillance, cancer was detected in 8 of 12 (66.7%) patients, with 2 of 12 (16.7%) found to have Gleason ≥3 + 4 = 7 prostate cancer. Additionally, cancer was detected in 13 of 31 (41.9%) patients undergoing a biopsy for prostate cancer screening, with 5 (16.1%) found to have Gleason ≥3 + 4 = 7 disease. In total, 3 (7.0%) patients experienced a postbiopsy complication: 2 (4.7%) with urinary retention and 1 (2.3%) with gross hematuria requiring catheterization. No patient experienced an infectious complication despite omission of periprocedural antibiotics in all cases. CONCLUSION The PrecisionPoint device allowed for the successful performance of in-office transperineal prostate biopsies under local anesthesia without the need for periprocedural antibiotics. We observed an acceptable cancer detection rate with no infectious complications.

Shifting the Paradigm of Testosterone Replacement Therapy in Prostate Cancer

Historically, testosterone and prostate cancer have been demonstrated to have a positive association leading providers to forgo testosterone replacement therapy (TRT) in men with concurrent histories of hypogonadism and prostate cancer. This paradigm has been gradually shifting with our evolving understanding of the relationship between testosterone and prostate cancer and the gaining popularity of the saturation model. Newer data suggests improved quality of life for men with hypogonadism after TRT leading to a more tempered view of the effects of this treatment and its risk in prostate cancer. As more reports emerge of TRT in men who have either undergone definitive treatment for prostate cancer or are on active surveillance, some providers see a role for TRT in these patients despite non-consensus in clinical guidelines. It is critical that we examine evidence currently available, while we await more rigorous data to emerge.

Ex vivo culture of tumor cells from N-methyl-N-nitrosourea-induced bladder cancer in rats: Development of organoids and an immortalized cell line

OBJECTIVE We ex vivo cultured primary tumor cells from N-methyl-N-nitrosourea (MNU)-induced bladder tumors in rats and established an immortalized cell line from them. MATERIALS AND METHODS Bladder tumors in rats were induced by instillation of MNU into the murine bladder. Primary tumor cells were prepared by the cancer-tissue originated spheroid method. An immortalized cell line was established by co-culture with fibroblasts. The cultured tumor cells were molecularly and functionally characterized by quantitative real-time polymerase chain reaction, Western blot, growth assay, and transwell migration assay. RESULTS Primary tumor cells were successfully prepared as multicellular spheroids from MNU-induced bladder tumors. The differentiation marker expression patterns observed in the original tumors were largely retained in the spheroids. We succeeded in establishing a cell line from the spheroids and named it T-MNU-1. Although basal markers (CK14 and CK5) were enriched in T-MNU-1 compared to the spheroids, T-MNU-1 expressed both luminal and basal markers. T-MNU-1 was able to migrate through a transwell. CONCLUSIONS Tumor cells in MNU-induced bladder tumors were successfully cultured ex vivo as organoids, and an immortalized cell line was also established from them. The ex vivo models offer a platform that enables analysis of intrinsic characteristics of tumor cells excluding influence of microenvironment in MNU-induced bladder tumors.