Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Triple Threat: Three Primary Malignancies Simultaneously Involving Three Genitourinary Organs.

Statistically, the chance of having concurrent renal cell carcinoma (RCC), urothelial carcinoma of the bladder (UC), and a neuroendocrine tumor (NET) of the renal parenchyma is less than one in a trillion. Herein, we describe an unusual case of a 67-year-old female who presented with bilateral flank pain and severe gross hematuria. Cross-sectional imaging revealed two large heterogeneous, endophytic renal masses with a single enlarged paracaval lymph node. Diagnostic cystoscopy was performed for completion of gross hematuria evaluation and revealed a concurrent papillary bladder tumor. Percutaneous biopsies of bilateral renal masses revealed clear cell RCC involving the left kidney and well-differentiated NET involving the right kidney, and transurethral resection of the bladder tumor revealed high-grade nonmuscle invasive urothelial carcinoma. The patient elected to undergo bilateral nephroureterectomy, radical cystectomy, and retroperitoneal and pelvic lymphadenectomy. Final pathology confirmed the presence of three different malignancies: noninvasive high-grade papillary UC of the bladder (pTaN0), left renal clear cell RCC (pT2bN0), right renal well-differentiated NET, and a single paracaval lymph nodes positive for metastatic NET (pT2aN1).

Survival outcomes in node-positive non-metastatic bladder cancer: An analysis of the national cancer database.

Introduction: Clinically node-positive non-metastatic bladder cancer (cN+) has been the target of several studies aiming to establish a standard of care for this population. Limited studies have shown a survival benefit for various multimodal therapy approaches. The role of radiation therapy has not been well established. Our study aims to study the trends of the reported treatment options offered to patients with cN+ bladder cancer in a national database and to evaluate the effect of various treatments, including radiation, on survival. Methods: The National Cancer Database (NCDB) was used to identify cN+ bladder cancer patients who received chemotherapy alone or in combination with radical cystectomy (RC) or radiotherapy. 3,481 patients were included and divided into 4 groups: chemotherapy only, chemotherapy and RC, chemotherapy and radiation therapy, and chemotherapy, RC, and radiation therapy. Demographic data was compared using ANOVA for continuous variables, and Chi-square for categorical variables. Multivariable analysis was done to compare groups using a multinomial logistic regression model. Kaplan-Meier test was used for survival analysis and Cox-Regression was used for multivariable survival analysis. Results: Patients undergoing RC were significantly younger (P <0.001). There was a significant difference between the groups regarding racial distribution, facility-type and insurance status. There was no difference in gender, Charlson\Deyo score, financial or educational status. Patients who underwent combination therapy with chemotherapy and RC were found to have the longest median survival time at 27 months. Multivariable analysis showed that final treatment, age, sex, Charlson\Deyo comorbidity score, TNM edition and facility-type were significant survival predictors. Race, insurance and financial status failed to maintain significance. There was no survival difference between the chemotherapy group and chemo-radiotherapy group. Conclusions: The combination of surgery and chemotherapy achieves statistically significant superior survival in cN+ bladder cancer. Adding radiotherapy to chemotherapy did not improve survival in this group of patients. Abbreviations: (cN+): Clinically node-positive non-metastatic, (MIBC): Muscle invasive bladder cancer, (NCDB): National Cancer Database, (NAC): Neoadjuvant chemotherapy, (RC): Radical Cystectomy.

Crisis Averted: Clinical T1b Renal Mass with Concurrent Arteriovenous Malformation and Renal Vein Thrombus.

Arteriovenous malformations (AVMs) secondary to renal-cell carcinoma (RCC) are well-described in the literature. Independently, renal vein and inferior vena cava tumor thrombi can be detected in locally-advanced RCC. A 67-year-old gentleman presented with a cT1b renal mass detected on workup for elevated creatinine. Multiphase CT imaging obtained for partial nephrectomy surgical-planning revealed an initially-missed renal cortical AVM. This drastically changed the plan for intervention, including use of an open approach with AVM embolization by interventional radiology prior and avoidance of a nephron-sparing approach. Final pathology confirmed the AVM and a subclinical renal vein thrombus masked by arterial flow on CT imaging, making this the first concurrent case described in the literature. Herein, we describe avoidance of catastrophic intraoperative hemorrhage by careful review of preoperative imaging and provide a literature review of imaging modalities for both renal surgical-planning and detection of tumor thrombi in RCC.

Evaluation of a nitinol stone retrieval basket as an alternative to biopsy forceps for biopsy of suspected upper tract genitourinary malignancies.

Background: The anatomical nature of the ureteroscopic approach for biopsy of upper urothelial tract tumors requires the utilization of small instruments, often limiting biopsy specimen quality. This leads to lower-than-desired tumor grading accuracy and malignancy detection capabilities on the initial evaluation of upper tract tumor specimens. This is problematic because optimal treatment of upper tract urothelial carcinoma (UTUC) depends on early disease detection and subsequent accurate diagnosis. Objective: The objective of our study was to compare the biopsy capabilities of two ureteroscopic biopsy instruments - biopsy forceps and the nitinol stone retrieval basket. Methods: We performed a retrospective analysis of ten patients who underwent biopsy of an upper tract mass with either instrument. Average specimen size, muscularis propria presence, and malignancy detection sensitivity were the variables of interest. Results: The nitinol stone retrieval basket obtained larger biopsy samples than the biopsy forceps, with average biopsy volumes being 0.0674 cm3 and 0.0075 cm3, respectively (P = 0.00017); this was the only statistically significant result of our study. Muscularis propria was present in 31% (4/13) of the biopsies with the nitinol stone retrieval basket, whereas 0% (0/5) of the biopsy forceps biopsies contained muscularis propria (P = 0.2778). Regarding malignancy detection sensitivity, the nitinol stone retrieval basket biopsies identified malignancy in 100% of the specimens that had confirmed malignancy; the biopsy forceps only detected malignancy 40% of the time (P = 0.4134). Conclusion: These findings suggest that the nitinol stone retrieval basket is a useful diagnostic tool for UTUC, although further investigation is warranted to determine its superiority compared to biopsy forceps.

Diagnostic dilemmas: a multi-institutional retrospective analysis of adrenal incidentaloma pathology based on radiographic size.

INTRODUCTION/BACKGROUND: Adrenal incidentalomas (AIs) are masses > 1 cm found incidentally during radiographic imaging. They are present in up to 4.4% of patients undergoing CT scan, and incidence is increasing with usage and sensitivity of cross-sectional imaging. Most result in diagnosis of adrenal cortical adenoma, questioning guidelines recommending removal of all AIs with negative functional workup. This retrospective study analyzes histological outcome based on size of non-functional adrenal masses. MATERIAL AND METHODS: 10 years of data was analyzed from two academic institutions. Exclusion criteria included patients with positive functional workups, those who underwent adrenalectomy during nephrectomy, < 18 years, and incomplete records. AI radiologic and histologic size, histologic outcome, laterality, imaging modality, gender, and age were collected. T-test was used for comparison of continuous variables, and the two-sided Fisher's exact or chi-square test were used to determine differences for categorical variables. Univariate analysis of each independent variable was performed using simple logistic regression. RESULTS: 73 adrenalectomies met the above inclusion criteria. 60 were detected on CT scan, 12 on MRI, and one on ultrasound. Eight of 73 cases resulted in malignant pathology, 3 of which were adrenocortical carcinoma (ACC). Each ACC measured > 6 cm, with mean radiologic and pathologic sizes of 11.2 cm and 11.3 cm. Both radiologic and pathologic size were significant predictors of malignancy (p = 0.008 and 0.011). CONCLUSIONS: Our results question the generally-accepted 4 cm cutoff for excision of metabolically-silent AIs. They suggest a 6 cm threshold would suffice to avoid removal of benign lesions while maintaining sensitivity for ACC.

Implementation of a Standardized Renal Trauma Protocol at a Level 1 Trauma Center: 7-Year Protocol and 10-Year Institutional Review.

Objective: Current urologic renal trauma guidelines favor conservative management. In 2012, we implemented an institution-wide renal trauma protocol to standardize management. This protocol details initiation of DVT (deep vein thrombosis) prophylaxis, cessation of bed rest, and frequency of laboratory studies. We hypothesized that low-grade injuries (grade I-III) could be managed without urologic consultation and that our chemical DVT prophylaxis regimen would not pose an increased risk of hemorrhage requiring transfusion. Methods: We performed a cross-sectional analysis of a prospectively maintained database containing all renal trauma at our institution from 2009 to 2019. We segregated injuries based on grade, presence of multi-organ trauma, and evaluated the presence and types of intervention, initiation of chemical DVT prophylaxis, and post-DVT prophylaxis hemorrhage requiring transfusion. Results: We identified 295 cases of renal trauma, of which 62 were isolated injuries. Forty-three of the isolated renal injuries were transferred from outside facilities, 70% of which were classified as low-grade injuries. There were 220 low-grade lacerations and 75 high-grade lacerations. No grade I or II lacerations required any interventions. Two (2.5%) grade III lacerations required IR embolization. Twenty-five (41%) grade IV lacerations required intervention, of which five were nephrectomy. Seven (54%) grade V lacerations required intervention, of which 5 were nephrectomies. Upon review of our protocol with early ambulation and DVT prophylaxis, there were no cases of isolated renal injury where initiation of either treatment resulted in delayed hemorrhage requiring transfusion or surgical intervention. Conclusion: Only 2/220 low-grade renal lacerations required intervention. Our data suggest that grade I and II renal lacerations can be managed safely without urologic consultation. Consultation is warranted for grade III injuries given the possibility of initial understaging. Furthermore, we believe our renal laceration protocol in our admittedly small, isolated sample has shown our DVT prophylaxis initiation to not pose increased risk.

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

Prognostic predictors of lymph node metastasis in penile cancer: a systematic review

ABSTRACT Purpose: Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with significant morbidity and mortality. A crucial prognostic factor is the presence of inguinal lymph node metastases (ILNM) at the time of diagnosis. At least 25% of cases have micrometastases at the time of diagnosis. Therefore, we performed a literature review of studies evaluating factors, both clinical and pathological, predictive of lymph node metastases in penile SCC. Materials and methods: Studies were identified using PubMed and search terms included the following: penile cancer, penile tumor, penile neoplasm, penile squamous cell carcinoma, inguinal lymph node metastasis, lymph node metastases, nodal metastasis, inguinal node metastasis, inguinal lymph node involvement, predictors, and predictive factor. The number of patients and predictive factors were identified for each study based on OR, HR, or RR in multivariate analyses, as well as their respective significance values. These were compiled to generate a single body of evidence supportive of factors predictive of ILNM in penile SCC. Results: We identified 31 studies, both original articles and meta-analyses, which identified factors predictive of metastases in penile SCC. The following clinical factors were predictive of ILNM in penile SCC: lymphovascular invasion (LVI), increased grade, increased stage (both clinical and pathological), infiltrative and reticular invasion, increased depth of invasion, perineural invasion, and younger patient age at diagnosis. Biochemically, overexpression of p53, SOD2, Ki-67, and ID1 were associated with spread of SCC to inguinal lymph nodes. Diffuse PD-L1 expression, increased SCC-Ag expression, increased NLR, and CRP >20 were also associated with increased ILNM. Conclusions: A multitude of factors are associated with metastasis of SCC of the penis to inguinal lymph nodes, which is associated with poor clinical outcomes. The above factors, most strongly LVI, grade, and node positivity, may be considered when constructing a nomogram to risk-stratify patients and determine eligibility for prophylactic inguinal lymphadenectomy.

The utilization of perfused cadaver simulation in urologic training: a pilot study.

BACKGROUND: We sought to determine if participating in a surgical training session using perfused fresh human cadavers (PFHC) had a positive effect on urology residents' confidence in performing open and endoscopic procedures. METHODS: Urology residents at our institution participated in a surgical training session in the West Virginia University Fresh Tissue Training Program, which utilized fresh cadavers with vascular perfusion. The session consisted of performing different urologic procedures (open and endoscopic) on the perfused fresh human cadavers (PFHC). Residents were given a survey to rate their confidence in different urologic procedures before, after, and 6 months after the session. Each procedure on the survey had 3-6 questions associated with it, with scores ranging from 0 (no confidence) to 4 (great confidence). Scores for each procedure before and after the session were compared. RESULTS: Six residents participated in the session. There was an increase in the score for every procedure performed after the session. Scores at 6 month follow up remained higher than the pre-session scores. CONCLUSION: PFHCs offer an excellent opportunity to teach a wide variety of urologic procedures to residents. Incorporation of PFHCs may be very useful in urologic training, and further studies on its use are warranted.

Prognostic predictors of lymph node metastasis in penile cancer: a systematic review.

PURPOSE: Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with significant morbidity and mortality. A crucial prognostic factor is the presence of inguinal lymph node metastases (ILNM) at the time of diagnosis. At least 25% of cases have micrometastases at the time of diagnosis. Therefore, we performed a literature review of studies evaluating factors, both clinical and pathological, predictive of lymph node metastases in penile SCC. MATERIALS AND METHODS: Studies were identified using PubMed and search terms included the following: penile cancer, penile tumor, penile neoplasm, penile squamous cell carcinoma, inguinal lymph node metastasis, lymph node metastases, nodal metastasis, inguinal node metastasis, inguinal lymph node involvement, predictors, and predictive factor. The number of patients and predictive factors were identified for each study based on OR, HR, or RR in multivariate analyses, as well as their respective significance values. These were compiled to generate a single body of evidence supportive of factors predictive of ILNM in penile SCC. RESULTS: We identified 31 studies, both original articles and meta-analyses, which identified factors predictive of metastases in penile SCC. The following clinical factors were predictive of ILNM in penile SCC: lymphovascular invasion (LVI), increased grade, increased stage (both clinical and pathological), infiltrative and reticular invasion, increased depth of invasion, perineural invasion, and younger patient age at diagnosis. Biochemically, overexpression of p53, SOD2, Ki-67, and ID1 were associated with spread of SCC to inguinal lymph nodes. Diffuse PD-L1 expression, increased SCC-Ag expression, increased NLR, and CRP >20 were also associated with increased ILNM. CONCLUSIONS: A multitude of factors are associated with metastasis of SCC of the penis to inguinal lymph nodes, which is associated with poor clinical outcomes. The above factors, most strongly LVI, grade, and node positivity, may be considered when constructing a nomogram to risk-stratify patients and determine eligibility for prophylactic inguinal lymphadenectomy.

Rare late presentation of bilateral single system intravesical ureteroceles complicated with ureterolithiasis: Case report and literature review.

Bilateral intravesical ureteroceles is a rare condition where both ureters terminally end in cystic dilations in the urinary bladder. Herein, a 31-year-old male patient presented with severe right flank pain and gross hematuria. Upon computed tomography imaging, a right ureterocele with an entrapped stone was revealed. Direct visualization also showed a smaller ureterocele at the left ureterovesical junction. Both ureteroceles were unroofed using rigid resectoscope with cold knife resulting in rapid bilateral efflux. The treatment was well tolerated with no known complications. Albeit uncommon, this case highlights the need to consider ureteroceles in adult patients with urinary tract symptoms.

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.

Use of SPY Elite Fluorescence Imaging in Creation of a Continent Urinary Diversion.

The use of SPY Elite Fluorescence Imaging has recently grown popular among multiple surgical specialties, including colorectal, plastic, endocrine, ophthalmologic, and vascular surgery, due to its ability to quickly and accurately assess tissue perfusion and guide intraoperative decision making. To our knowledge, the use of SPY imaging in urologic reconstructive surgery has yet to be reported. We present a case in which SPY imaging was used intraoperatively to assess perfusion of an ileocecal anastomosis and a segment of bowel prior to creation of a continent urinary diversion following radical cystectomy.

Locally Recurrent Leiomyoma of the Bladder Refractory to Visually Complete Transurethral Resection: An Indication for Cystoprostatectomy.

Leiomyomas are benign smooth muscle tumors that have low malignant potential (0.1%) and can arise in nearly any area of the body. Genitourinary involvement is very rare and represents only 0.05% of all bladder tumors (Mendes et al., 2017; GÖK, 2017). The most common presenting symptoms of bladder leiomyomas are obstructive voiding (49%), irritative voiding (38%), and hematuria (11%) (Goluboff et al., 1994). Treatment involves complete excision, in this case transurethral resection (TUR), and generally results in complete cure with no recurrences noted in the 250 cases reported in the literature for open resection and 18% recurrence rates after TUR which were successfully treated with a repeat TUR in all cases. Herein, we report a case of leiomyoma of the bladder which was refractory to four visually complete transurethral resections and ultimately required radical cystoprostatectomy with ileal conduit urinary diversion.

Unusual Mechanisms of Penile Amputation.

Penile amputation is an uncommon and highly morbid injury. Many mechanisms have been reported ranging from self-mutilation and domestic violence to traumatic circumcisions. We present two unusual cases of traumatic penile amputation. An older gentleman endured extensive perineal trauma after being trapped underneath an industrial-sized lawnmower, and a young adolescent was bitten by an English bulldog and suffered amputation of the glans of his penis. These unique and very different cases of penile amputation highlight differences in operative managements, complications, and reconstructive possibilities.

Sociodemographic and Provider Based Disparities in the Management of Stage I Testicular Cancer.

INTRODUCTION: The treatment paradigm for stage I testicular cancer has changed in the setting of accurate staging, reliable followup and a greater understanding of treatment related side effects. We assessed the influences on management decisions in patients with stage I testicular cancer. METHODS: We retrospectively identified 121 patients with stage I testicular cancer who were evaluated at our institution from 1999 to 2013. Sociodemographic characteristics, pathological features and provider specific factors were compared in patients who underwent surveillance vs treatment. Differences in medians and proportions were determined using the Kruskal-Wallis and chi-square tests. Multivariate logistic regression analysis was performed to identify independent predictors of treatment. RESULTS: A total of 87 patients had stage I nonseminomatous germ cell tumor and 34 had pure seminoma. Patients with nonseminomatous germ cell tumor who were evaluated before 2011 and those seen by urological oncologists were more likely to undergo primary retroperitoneal lymph node dissection (p <0.01). Patients with nonseminomatous germ cell tumor who were evaluated by medical oncologists more often received chemotherapy (p <0.01). For nonseminomatous germ cell tumors treatment was independently associated with advanced tumor stage and lymph node invasion (OR 15.3, 95% CI 3.26-71.95, p = 0.001). In patients with pure seminoma the use of radiation therapy decreased from 40% to 5% after 2010 while surveillance increased from 47% to 74% (p = 0.056) and no recorded variable was predictive of treatment. CONCLUSIONS: Advanced stage and lymph node invasion in patients with stage I nonseminomatous germ cell tumor are drivers of treatment. Management also depends on the specialty of the treating provider, suggesting the possibility of bias during patient counseling. In turn, this suggests the need for patient assessment through a multidisciplinary approach.

Change in Management Based on Pathologic Second Opinion Among Bladder Cancer Patients Presenting to a Comprehensive Cancer Center: Implications for Clinical Practice.

OBJECTIVE: To evaluate the incidence and degree of change from a pathologic second opinion of bladder biopsies at a Comprehensive Cancer Center that were initially performed at referring community hospitals. The secondary objective was to determine the impact the potential changes would have on a patient's treatment. MATERIALS AND METHODS: Dedicated genitourinary pathologists reviewed 1191 transurethral biopsies of the bladder and/or prostatic urethra from 2008 to 2013. Major and minor treatment changes were defined as altering recommendations for cystectomy, systemic chemotherapy, or primary cancer diagnosis, and alterations in intravesical regimens, respectively. RESULTS: There were 326/1191 patients (27.4%) with a pathologic change on second opinion: grade (62/1191, 5.2%), stage (115/1191, 9.7%), muscle in the specimen (29/1191, 2.4%), presence or absence of carcinoma in situ (34/1191, 2.9%). Outside pathology did not address the presence or absence of lymphovascular invasion in 620/759 (81.7%) of invasive cases (≥cT1), of which 35/620 (5.6%) had lymphovascular invasion. There were 212 mixed, variant, or nonurothelial histologies detected in 199/1191 (16.7%) patients, with 114/212 (53.7%) resulting in reclassification by our pathologists. Potential treatment alterations accounted for 182/1191 (15.3%) of cases, with 141/1191 (11.8%) imparting major changes. There were 82/1191 (6.8%) changes in recommendation for a radical cystectomy, 38/1191 (3.2%) had a complete change in primary tumor type, and 21/1191 (1.8%) for change in chemotherapy regimen. CONCLUSION: The amount and degree of pathologic changes and its potential impact on treatment emphasize the importance of bladder cancer patients having their histology reviewed by genitourinary-dedicated pathologists. In our cohort, 15.3% of patients could see a treatment alteration, with 11.8% being a major change.

Long term survival and predictors of disease reclassification in patients on an active surveillance protocol for prostate cancer.

INTRODUCTION: Up to 50% of patients will have disease reclassification while on active surveillance (AS) for their prostate cancer. Determining which patients will have reclassification that will impact their survival is difficult. We investigated clinicopathologic factors associated with disease reclassification and differences in both overall and metastasis free survival between those treated and those remaining on AS. MATERIALS AND METHODS: We performed a retrospective review of patients who were enrolled in an AS protocol between 1994 and 2000. Inclusion criteria for AS were: < cT2a disease, PSA < 10 ng/mL, < 50% of single core involvement, and Gleason score < 7, as well as sufficient follow up for evaluation (at least 1 subsequent transrectal ultrasound guided biopsy after initial diagnosis). RESULTS: There were 102 patients that met the inclusion criteria with median age of 70 years (IQR 68-73), follow up of 9.25 years (IQR 6.1-12.2) and time to disease reclassification of 4.7 years (IQR 2.8-7.9). Only prostate-specific antigen (PSA) density ≥ 0.15 was a significant predictor of disease reclassification with a hazard ratio of 5.5 (95% confidence interval 2.3-13.4, p < 0.01). There was no significant difference in metastasis free and overall survival between patients who received treatment and those that continued on AS despite reclassification of disease; this remained true even while stratifying patients by age ≥ 70 compared to those < 70 years old. CONCLUSIONS: PSA density is a significant predictor of disease reclassification and AS remains a safe option for patients with low risk prostate cancer with up to 10 years of follow up.