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PURPOSE According to National Comprehensive Cancer Network guidelines, adjuvant chemotherapy (AC) has been advocated after primary retroperitoneal lymph node dissection (RPLND) to reduce the risk of relapse in pathologic nodal (pN) stage pN2 or pN3, whereas surveillance is preferred for pN1. We sought to explore the oncologic efficacy of primary RPLND alone for pathologic stage II in nonseminomatous germ cell tumors (NSGCTs) to reduce overtreatment with chemotherapy. METHODS Patients with pathologic stage II NSGCT after primary RPLND between 2007 and 2017 were identified. Patients were excluded for elevated preoperative serum tumor markers, receipt of AC, or if pure teratoma or primitive neuroectodermal tumor elements were found in the retroperitoneal pathology. RESULTS We identified 117 patients with active NSGCT in the retroperitoneum after primary RPLND. We excluded seven patients who lacked meaningful follow-up and 13 patients who received AC. There were 97 patients treated with RPLND alone: 41 pN1, 46 pN2, and 10 pN3. In total, 77 of 97 patients had not recurred after a median follow-up time of 52 months. The 2-year recurrence-free survival (RFS) was 80.3%, and the 5-year RFS was 79%. No differences in RFS were noted among nodal stage—pN1, pN2, and pN3—on Kaplan-Meier analysis. Lymphovascular invasion in the orchiectomy specimen, a high-risk pathologic feature, was also predictive of recurrence after primary RPLND. All 20 patients who recurred were treated with first-line chemotherapy and remained continuously disease free. CONCLUSION Most men with pathologic stage II disease treated with surgery alone in our series never experienced a recurrence. We did not observe a difference in recurrences between patients with pN1 and pN2. The recommendation for AC for pN2 disease may be overtreatment in most patients.

Supplementary Table S2: Cystectomy Pathologic Staging

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Purpose: To assess the clinical and pharmacodynamic activity of dovitinib in a treatment-resistant, molecularly enriched non–muscle-invasive urothelial carcinoma of the bladder (NMIUC) population.Experimental Design: A multi-site pilot phase II trial was conducted. Key eligibility criteria included the following: Bacillus Calmette-Guerin (BCG)-unresponsive NMIUC (>2 prior intravesical regimens) with increased phosphorylated FGFR3 (pFGFR3) expression by centrally analyzed immunohistochemistry (IHC+) or FGFR3 mutations (Mut+) assessed in a CLIA-licensed laboratory. Patients received oral dovitinib 500 mg daily (5 days on/2 days off). The primary endpoint was 6-month TURBT-confirmed complete response (CR) rate.Results: Between 11/2013 and 10/2014, 13 patients enrolled (10 IHC+ Mut−, 3 IHC+ Mut+). Accrual ended prematurely due to cessation of dovitinib clinical development. Demographics included the following: median age 70 years; 85% male; carcinoma in situ (CIS; 3 patients), Ta/T1 (8 patients), and Ta/T1 + CIS (2 patients); median prior regimens 3. Toxicity was frequent with all patients experiencing at least one grade 3–4 event. Six-month CR rate was 8% (0% in IHC+ Mut−; 33% in IHC+ Mut+). The primary endpoint was not met. Pharmacodynamically active (94–5,812 nmol/L) dovitinib concentrations in urothelial tissue were observed in all evaluable patients. Reductions in pFGFR3 IHC staining were observed post-dovitinib treatment.Conclusions: Dovitinib consistently achieved biologically active concentrations within the urothelium and demonstrated pharmacodynamic pFGFR3 inhibition. These results support systemic administration as a viable approach to clinical trials in patients with NMIUC. Long-term dovitinib administration was not feasible due to frequent toxicity. Absent clinical activity suggests that patient selection by pFGFR3 IHC alone does not enrich for response to FGFR3 kinase inhibitors in urothelial carcinoma. Clin Cancer Res; 23(12); 3003–11. ©2016 AACR.

PURPOSE On the basis of National Comprehensive Cancer Network guidelines, clinical stage (CS) II seminoma is treated with radiotherapy or chemotherapy. Primary retroperitoneal lymph node dissection (RPLND) demonstrated recent success as first-line therapy for RP-only disease. Our aim was to confirm surgical efficacy and evaluate recurrences after primary RPLND for CS IIA/IIB seminoma to determine if various clinical factors could predict recurrences. PATIENTS AND METHODS Patients who underwent primary RPLND for seminoma from 2014 to 2021 were identified. All patients had at least 6 months of follow-up. Nineteen patients were part of a clinical trial. Patients receiving adjuvant chemotherapy were excluded from Kaplan-Meier recurrence-free survival (RFS) analysis. RESULTS We identified 67 patients who underwent RPLND for RP-only seminoma. One patient had pN0 disease. Median follow-up time after RPLND was 22.4 months (interquartile range, 12.3-36.1 months) and 11 patients were found to have a recurrence. The 2-year RFS for RPLND-only patients without adjuvant chemotherapy was 80.2%. Patients who developed RP disease for a period > 12 months had the lowest chance of recurrence, with a 2-year RFS of 92.2%. Seven initial CS II patients were on surveillance for 3-12 months before surgery and no patients experienced recurrence. Pathologic nodal stage and high-risk factors such as tumor size > 4 cm or rete testis invasion of the orchiectomy specimen did not affect recurrence. CONCLUSION CS II seminoma can be treated with surgery to avoid rigors of chemotherapy or radiotherapy. Patients with delayed development of CS II disease (> 12 months) had the best surgical results. Patients may present with borderline CS II disease, and careful surveillance may avoid overtreatment. Further study on patient selection and extent of dissection remains uncertain and warrants further investigation.

The year 2020 will be remembered for a number of different events, both good and bad. For the journal Urologic Oncology, Seminars and Original Investigations, this year represents the 25th anniversary of its inception and 1st publication. Under the encouragement of Editor-in-Chief Dr. Michael Droller, the collective editorial board has put together a reflection of the progresses made among the spectrum of genitourinary cancers across the entirety of therapeutic disciplines. In this review, we discuss the advances achieved in our knowledge and understanding of testicular germ cell tumors since 1995, and the challenges that lie ahead.

Objective To characterize the health-related quality of life reported by patients who received an ileal conduit (IC), Indiana pouch, or neobladder urinary diversion after radical cystectomy. Materials and Methods The Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index survey was administered to patients with bladder cancer undergoing radical cystectomy and urinary diversion from 2015-2018. Surveys were completed prior to radical cystectomy and then longitudinally throughout the postoperative course. Results A total of 146 patients completed questionnaires over a median of 12.3 months, 83 (56.8%) received an IC, 31 (21.2%) an Indiana pouch, and 32 (21.9%) an orthotopic neobladder. There were no significant differences in health related quality of life among urinary diversion groups considering the Trial Outcome Index scores, general overall FACT-G assessment, or total Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index instruments. Patients who received IC were older and had higher Charlson Comorbidity Index scores (p Conclusions To our knowledge this is the first and largest quality of life analysis comparing all three methods of urinary diversion in a longitudinal fashion utilizing a standardized, validated, treatment-specific health survey. Proper preoperative counseling is critical to ensure understanding of the benefits of available urinary diversion.

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. info:eu-repo/semantics/publishedVersion

We analyzed the oncologic outcomes of men undergoing primary retroperitoneal lymph node dissection and characterized the use of adjuvant chemotherapy and template dissections.Retrospective review of the Indiana University testis cancer database identified patients who underwent primary retroperitoneal lymph node dissection between January 2007 and December 2017. Patients and providers were contacted to obtain information regarding adjuvant therapy, recurrence and survival. The primary outcome was recurrence-free survival. Kaplan-Meier curves assessed survival differences stratified by pathological stage, template of dissection and use of adjuvant chemotherapy.A total of 274 patients were included in the study. Most men presented with clinical stage I disease (214, 78%). A modified unilateral template was performed in 257 (94%) and bilateral template in 17 (6%). Overall 148 (54%) and 126 (46%) men had pathological stage (PS) I and PS-II disease, respectively. Thirteen patients (10%) with PS-II disease were treated with adjuvant chemotherapy. With a median followup of 55 months only 33 (12%) patients had recurrence. Of the 113 patients with PS-II disease who did not receive chemotherapy 21 (19%) had disease relapse and 81% were cured with surgery alone and never had recurrence. No difference in recurrence-free survival was noted between modified and bilateral template dissections.The use of adjuvant chemotherapy has been minimal during the last decade. The majority (81%) of men with PS-II disease were cured with retroperitoneal lymph node dissection alone and were able to avoid chemotherapy. Modified unilateral template dissection provided excellent oncologic control while minimizing morbidity.

Objective: To compare peri-operative factors and renal function following open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN) for intermediate and high complexity tumors when contr...

PURPOSE Presence of teratoma in patients with metastatic testicular germ cell tumor (GCT) is of unknown prognostic significance. We report survival outcomes of patients with or without teratoma in primary tumor and postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) specimen and assess impact on prognosis. PATIENTS AND METHODS Patients with metastatic nonseminomatous GCT (NSGCT) who were evaluated at Indiana University between 1990 and 2016 and had primary testicular tumor specimen from orchiectomy (ORCH) were included. All patients were treated with cisplatin-based combination chemotherapy. The cohort was divided into 2 groups according to presence or absence of teratoma in ORCH specimen. Survival data were correlated with histopathologic findings. Differences in progression-free (PFS) and overall survival (OS) were evaluated using log-rank tests and Cox proportional hazards models to adjust for known adverse prognostic factors. RESULTS We identified 1,224 consecutive patients evaluated at Indiana University between 1990 and 2016 who met inclusion criteria. Median age was 27 years (range, 13-71 years); 689 patients had teratoma in ORCH specimen, and 535 did not. With median follow-up of 2.3 years, 5-year PFS was 61.9% (95% CI, 57.1% to 66.2%) for those with teratoma versus 63.1% (95% CI, 58.0% to 67.8%) for those without ( P = .66); 5-year OS was 82.2% (95% CI, 77.9% to 85.8%) versus 81.4% (95% CI, 76.5% to 85.3%; P = .91), respectively. A total of 473 patients underwent PC-RPLND; 5-year PFS for patients with pure teratoma in PC-RPLND specimen versus necrosis only was 65.9% versus 79.1% ( P = .06), and 5-year OS was 90.3% versus 93.4% ( P = .21), respectively. CONCLUSION Presence of teratoma in ORCH and PC-RPLND specimens was not a prognostic factor in this large retrospective study of patients with NSGCT.

To determine the benefits of alvimopan and multimodal pain management strategies in men undergoing retroperitoneal lymph node dissection for testicular cancer.A retrospective cohort study was completed in men undergoing retroperitoneal lymph node dissection from January 2017 to May 2018. Patients were placed into the 3-drug, 2-drug, and control cohorts as a result of a prospectively determined protocol during the study period. Men in the 3-drug group were managed using alvimopan 12 mg PO the morning of surgery then BID until bowel movement, gabapentin 300 mg daily, and acetaminophen 1,000 mg q6H. The 2-drug group was managed with the above regimen excluding alvimopan. Controls were treated per our standard perioperative pathway. Primary outcomes were length of stay, IV narcotic consumption, bowel movement during hospitalization, and time to bowel movement and assessed in multivariate models controlling for operative time, concomitant surgery, chemotherapy receipt, and residual mass size.One-hundred and fifty-two consecutive patients underwent RPLND (42 3-drug, 38 2-drug, and 72 controls). Multivariable models indicated that the 3-drug (IRR 0.89, P0.0001) and 2-drug group (IRR 0.87, P = 0.0209) had shorter hospital stays than controls. Men in the 3-drug group required less narcotic pain medication than the 2-drug (β -8.16, P = 0.0405) and the control (β -8.16, P = 0.0302) group. Men receiving alvimopan (3-drug) were almost 6 times more likely than the 2-drug group (odds ratio 5.94, P0.0001) and 4 times more likely than the control group (odds ratio 3.86, P = 0.0017) to have a bowel movement during hospitalization. Men in the 3-drug group had the quickest return of bowel movements.Multimodal pain management improves length of stay in men undergoing retroperitoneal lymph node dissection for testis cancer. The addition of alvimopan allows for quicker return of bowel movements and reduces overall narcotic requirements.

Introduction and objective: Traditionally, patients with renal masses in solitary kidneys were managed with an open partial nephrectomy. With improving techniques, robotic-assisted partial nephrectomy in the setting of a solitary kidney is increasingly utilized. The objective of this study was to compare open partial nephrectomy and robotic-assisted partial nephrectomy outcomes in solitary kidney patients. Methods: A retrospective study of 536 total patients who underwent partial nephrectomy between 2004–2016 was performed. Of these patients, 23 had a renal mass in a solitary kidney. Patient demographics, perioperative values, and surgical outcomes were analyzed using descriptive statistics to compare open partial nephrectomy to robotic-assisted partial nephrectomy. Results: Of the 23 patients in the cohort, 52% ( n=12) underwent open partial nephrectomy and 48% ( n=11) underwent robotic-assisted partial nephrectomy. Patient characteristics were not significantly different. The mean (standard deviation) nephrometry score was 6.9 (1.8) for open partial nephrectomy and 6.1 (1.9) for robotic-assisted partial nephrectomy ( p=0.290). The mean (standard deviation) pre-operative creatinine was 1.2 (0.3) in open partial nephrectomy and 1.5 (0.4) in robotic-assisted partial nephrectomy, which did not reach statistical significance ( p=0.110). No difference in postoperative kidney function, Clavien grade 3 or higher complication rate, blood loss, or hospitalization length was noted. Conclusion: Although traditionally patients with a tumor in a solitary kidney are counseled to undergo open partial nephrectomy, robotic-assisted partial nephrectomy is a safe alternative with no decrease in postoperative renal function when compared with a similar cohort of patients undergoing open partial nephrectomy in a solitary kidney. Level of evidence: Level II

The purpose of this review is to present a comprehensive and updated review of the literature and summary of the indications, risks and outcomes related to salvage, desperation and late relapse surgery for advanced testicular cancer. After completing a thorough review of the current literature, this review has attempted to provide an overview of the indications for salvage, desperation and late relapse retroperitoneal lymph node dissection (RPLND) followed by a summary of the histopathologic and clinical outcomes regarding each. Recent literature, combined with a significant contribution from historical studies suggest that while testicular cancer is a relatively uncommon malignancy overall, it represents the most common solid organ malignancy for young men. Although a significant number of men are cured with a combination of first-line treatments, the remaining men are a diverse and often challenging cohort who require the benefit of expertise to improve their outcomes. The role of surgical strategies in the salvage, desperation and late relapse settings is unquestionable, although the most important question remains who will benefit. This often requires a multi-disciplinary approach at centers specializing in this disease process in order to recognize who should get surgery, what surgery to do and how to minimize the potential morbidity associated with the operation.

INTRODUCTION AND OBJECTIVE:Adjuvant chemotherapy (AC) has been advocated after primary retroperitoneal lymph node dissection (RPLND) to reduce the historical 50% risk of relapse in pN2/N3 patients,...

Presence of teratoma in the orchiectomy and residual retroperitoneal mass size are known predictors of finding teratoma during postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). We sought to determine if the percentage of teratoma in the orchiectomy specimen could better stratify the risk of teratoma in the retroperitoneum.The Indiana University Testis Cancer Database was reviewed to identify patients who underwent PC-RPLND for nonseminomatous germ cell tumors from 2010 to 2018. A logistic regression model was fit to predict the presence of retroperitoneal teratoma using teratoma and yolk sac tumor in the orchiectomy, residual mass size and log transformed values of prechemotherapy alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin. The study cohort was split into 60% training and 40% validation sets using 200 bootstraps. A predictive nomogram was developed for predicting teratoma in the retroperitoneum.A total of 422 men were included. Presence of teratoma in the orchiectomy (OR 1.02, p0.001), residual mass size (OR 1.16, p0.001) and log transformed prechemotherapy AFP (OR 1.12, p=0.002) were predictive factors for having teratoma in the retroperitoneum. The C-statistic using this model demonstrated a predictive ability of 0.77. Training set C-statistic was 0.78 compared to 0.75 for the validation set. A nomogram was developed to aid in clinical utility.The model better predicts patients at higher risk for teratoma in the retroperitoneum following chemotherapy, which can aid in a more informed referral for surgical resection.

Testis cancer is the most common solid malignancy in young males. The purpose of this guideline is to provide a useful reference on the effective evidence-based treatment of early stage testicular cancer.The systematic review utilized to inform this guideline was conducted by a methodology team at the Johns Hopkins University Evidence-based Practice Center. The methodology team searched using PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The evidence review team also reviewed relevant systematic reviews and references provided by the panel to identify articles that may have been missed by the database searches.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low). Such evidence-based statements are provided as Strong, Moderate, or Conditional Recommendations. In instances of insufficient evidence, additional guidance is provided as Clinical Principles and Expert Opinions.This guideline attempts to improve a clinician's ability to evaluate and treat patients with testicular cancer, but higher quality evidence in future trials will be essential to improve level of care for these patients.

To investigate the clinical history of patients with clinical stage II sex cord stromal tumors who underwent retroperitoneal lymph node dissection (RPLND) at our institution.Our prospectively maintained testicular cancer database was queried to identify patients who presented with or developed clinical stage II sex cord stromal tumors and underwent RPLND at our institution between 1980 and 2018. Demographic, clinical, and pathologic characteristics were reviewed. Kaplan-Meier curves were graphed to assess recurrence-free and overall survival.Fourteen patients were included in the study with a median age of 44.2years. Four patients presented with clinical stage II disease and 10 patients developed metastatic disease during follow-up of initial clinical stage I disease with a median time to metastasis of 2.7years (range: 0.4-19.5 years). Of the 10 patients with orchiectomy pathology data available, all patients had at least 1 risk factor on testis pathology (mean: 2.9 risk factors). Nine patients received treatment prior to referral to our institution. All patients recurred post-RPLND at Indiana University. Median recurrence-free survival was 9.8 months. Twelve patients died of disease with a median overall survival of 14.4 months.Metastatic sex cord stromal tumors are rare and are more resistant to standard treatment modalities than metastatic germ cell tumors. Patients presenting with sex cord stromal tumors should consider prophylactic primary RPLND in the setting of 1 or more pathologic predictor of malignancy.

e17012 Background: Stage II seminoma is typically treated with radiotherapy or chemotherapy based on NCCN guidelines. Primary RPLND has demonstrated efficacy as first-line therapy for retroperitoneal (RP)-only disease. Our aim was to study recurrences of patients undergoing primary RPLND for Stage IIa or IIb seminoma to identify clinicopathologic factors affecting outcomes. Methods: Using our prospectively maintained database, we identified patients that had primary RPLND for seminoma from 2014-2021. All patients had at least 6 months of follow up. Patients were clinical stage IIa or IIb at the time of surgery and underwent open RPLND. We used Kaplan-Meier analysis for recurrence free survival (RFS) and compared clinicopathologic factors. Results: We identified 67 patients that underwent RPLND for RP only seminoma. Table shows the clinical characteristics of patients experiencing recurrences (median follow up - 22.4 months) and excludes 2 patients that had adjuvant chemotherapy. The 2-year RFS rate was 80.2%. Eleven patients (16.4%) experienced recurrences. Kaplan Meier analysis demonstrated improved survival in patients that had an RPLND after 12 months of surveillance (p = 0.02). Fifty-six patients were presumably cured with surgery alone at time of last follow-up. No patients died of testis cancer. One patient had a recurrence within the surgical field. Two patients had contralateral recurrences that may have been cured with bilateral RP template dissection. Seven patients that had a bilateral template dissection had disease on the contralateral side, of which 4 patients had visible nodes on pre-operative scans. In total, 9 out of 67 patients had disease on the contralateral side suggesting that bilateral RP template could confer higher cure rates. Recurrences were successfully treated with BEPx3 (9 pts), Redo RPLND then BEPx3 (1 pt), BEPx3 then High Dose chemotherapy (1 pt), and EPx4 (1 pt). Conclusions: Primary RPLND for low volume RP disease is effective with over 80% chance of surgical cure. Recurrences were cured almost exclusively with induction chemotherapy. Patients with delayed RP only recurrences had improved surgical success. Further investigation in larger trials may help standardize bilateral templates in seminoma and surveillance protocols in the post-operative setting. [Table: see text]

Residual retrocrural disease in testis cancer following chemotherapy is a surgical challenge. We sought to assess the outcomes and evolution with surgical management of residual retrocrural disease.We identified 2,788 testicular cancer patients from 1990 to 2010 who underwent retroperitoneal surgery for metastatic testicular cancer at our institution. Patients who also underwent postchemotherapy staged or concurrent retrocrural dissections were stratified for analysis. Surgical approach, clinical characteristics, additional procedures, complications and outcomes were evaluated.Retrocrural dissection was performed in 211 patients. Histology of retrocrural disease demonstrated teratoma in 72%, necrosis in 15.2%, active germ cell cancer in 8.1% and malignant transformation in 2.4%. Our preferred surgical approach to the retrocrural space has evolved over time. Earlier approaches from 1990 to 1995 favored a single thoracoabdominal incision (17, 25%), midline transabdominal incision (22, 32.4%), or with a concurrent or staged thoracotomy (29, 42.6%). A transabdominal/transdiaphragmatic approach at the time of midline retroperitoneal lymph node dissection has been used more frequently in 55% of contemporary cases, decreasing the need for thoracotomies. Patients undergoing a transabdominal/transdiaphragmatic approach had fewer complications (p=0.006) and required fewer associated procedures (p=0.001) and a shorter length of stay (5 vs 6 days, p=0.184).Metastatic testis cancer to the retrocrural space is surgically challenging however complete resection is needed to maintain an expected excellent oncologic outcome. Coordination between urological and thoracic surgeons for an individualized approach is important. We have found that a transabdominal/transdiaphragmatic approach where appropriate has resulted in fewer complications.

Gains of genetic material or internal rearrangements of chromosome 12p, including 12p overrepresentation or isochromosome 12p [i(12p)], are observed in virtually all germ cell tumors (GCT), in all histologic subtypes, and from various body locations. The chromosomal region involved in these alterations contains the growth and survival promoting oncogene KRAS (12p12.1). Gains or rearrangements of 12p characterize GCT from in situ to chemoresistant stages. Fluorescence in situ hybridization (FISH) detection of chromosome 12p anomalies is a sensitive and specific test for the diagnosis of germ cell tumors. Here we provide a detailed protocol for FISH detection of isochromosome 12p and chromosome 12p overrepresentation. The method is helpful for diagnosis of germ cell origin, and for selection of patients who may benefit from cisplatin-based chemotherapy.

Gains of genetic material or internal rearrangements of chromosome 12p, including 12p overrepresentation or isochromosome 12p [i(12p)], are observed in virtually all germ cell tumors (GCT), in all histologic subtypes, and from various body locations. The chromosomal region involved in these alterations contains the growth and survival promoting oncogene KRAS (12p12.1). Gains or rearrangements of 12p characterize GCT from in situ to chemoresistant stages. Fluorescence in situ hybridization (FISH) detection of chromosome 12p anomalies is a sensitive and specific test for the diagnosis of germ cell tumors. Here we provide a detailed protocol for FISH detection of isochromosome 12p and chromosome 12p overrepresentation. The method is helpful for diagnosis of germ cell origin, and for selection of patients who may benefit from cisplatin-based chemotherapy.

Coronavirus disease 2019 (COVID-19) is a global pandemic affecting hospital systems and the availability of resources for surgical procedures. Our aim is to provide guidance for urologists to help prioritize urological cancer surgeries.We reviewed published literature on bladder cancer, upper tract urothelial carcinoma, penile cancer, testis cancer, prostate cancer, renal cancer and adrenal cancer.For muscle invasive bladder cancer delays should be less than roughly 10 weeks and neoadjuvant chemotherapy should be considered. Patients with nonmuscle invasive bladder cancer should be counseled appropriately based on risk and intravesical therapies can continue. Upper tract urothelial carcinoma should also be treated with minimal delays for high risk patients, especially with ureteral tumors. Surgery for T1 renal cancers when indicated can be delayed until adequate resources are available. Patients with T2 renal cancer should be considered for early surgery if there are unfavorable preoperative characteristics. Higher stage renal tumors should be considered for early surgery. An early multidisciplinary approach is recommended for metastatic renal cancers. High risk prostate cancer may need preferential treatment and consideration of neoadjuvant hormonal therapy. Penile cancer can have worse sexual or oncologic outcomes with prolonged surgical delay. Likewise, adrenal cancer is aggressive and needs early surgical treatment. Testicular cancer should be treated in a timely manner with surgery or chemotherapy, as indicated.This review should further assist urologists in recognizing patients with potentially aggressive tumor biology that warrants early treatment.

Objectives To investigate the clinical characteristics and survival outcomes of a large clear cell papillary renal cell carcinoma cohort. Methods and Materials A retrospective review of patients with clear cell papillary renal cell carcinoma at a single academic center was performed after Institutional Review Board approval. Patients underwent either partial or radical nephrectomy from September 2009 to July 2019. Demographic and clinical characteristics, recurrence, and cancer specific and overall survival were reported. Results A total of 90 patients were included in the study. Median follow up was 26.5 months. Median age was 61 (range 27 to 87). 47.8% of patients were African American. 26.7% of patients had end stage renal disease. 37.8% had multifocal renal tumors. 48.9% underwent partial nephrectomy, while the remainder underwent radical nephrectomy. 43.3% underwent an open surgical approach, 40.0% a robotic approach, and 16.7% a laparoscopic approach. Pathologic stage included T1a (90.0%), T1b (1.1%), and T2b (8.9%). Fuhrman grades 1-3 were present in 18.9%, 77.8%, and 3.3% of patients, respectively. There were no cancer specific deaths. There was one local recurrence and no metastases. The overall survival at a median follow up of 26.5 months was 92.1% (95% confidence interval 83.1%–96.4%). Conclusions Clear cell papillary renal cell carcinoma typically presents at a low stage and grade and has favorable survival outcomes. A nephron-sparing approach to treatment should be considered when feasible due to the tumor's indolent nature and propensity towards multifocality.

The purpose of this study was to evaluate the effect of neoadjuvant chemotherapy (NACT) on squamous variant (SV) bladder cancer by investigating patients presenting with SV histology at the time of transurethral resection (TUR), stratified by their receipt of NACT.The records of 71 patients with muscle-invasive bladder cancer and SV in the TUR specimen who underwent cystectomy between 2008 and 2018 were reviewed. Our primary outcome was pathologic response at time of cystectomy. Secondary outcomes included recurrence-free survival and overall survival stratified by receipt of NACT. A subgroup analysis was then conducted on the patients with defined SV% on TUR stratified by % involvement (50% SV vs. ≥ 50% SV).The median age of the NACT and no-NACT groups was 60.2 and 70 years, respectively (P = .003). The complete response rate at cystectomy was 60% versus 13.7% for the NACT and no-NACT groups, respectively (P .001). The non-organ-confined disease rate at time of radical cystectomy was 35% for the NACT group and 68.6% for the no-NACT group (P = .01). The NACT group had fewer recurrences than the no-NACT group (10% vs 47.1%; P = .003). In the subgroup analysis, the lower rate of non-organ-confined disease persisted for the patients who underwent NACT at the lower SV percentage but failed to remain significant at greater percentage involvement. This was also true for overall survival.The effect of NACT in variant histology bladder cancer is variable. In patients with SV, these results favor the recommendation in favor of NACT administration, particularly when the primary tumor has 50% involvement by the variant histology.

INTRODUCTION AND OBJECTIVE:Complication rates following cystectomy range from 40-80% with 75% of complications being related to the urinary diversion. Reported complication following continent cuta...

Purpose Three cycles of bleomycin, etoposide, and cisplatin (BEP × 3) or four cycles of etoposide and cisplatin (EP × 4) are first-line chemotherapy regimens for men with International Germ Cell Cancer Collaborative Group (IGCCCG) good-risk germ cell tumors (GCTs). We determined whether inclusion of bleomycin affected pulmonary and operative morbidity after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). Patients and Methods We queried our database to identify IGCCCG good-risk patients who received BEP × 3 or EP × 4 induction chemotherapy before PC-RPLND from 2006 to 2016. Patients who received combination regimens were excluded. The primary outcomes of interest were pulmonary morbidity (prolonged intubation, reintubation, supplemental oxygen use, intensive care unit stay) and operative morbidity (operative time, length of stay, concomitant procedures, estimated blood loss). Results We analyzed 234 patients (191 BEP × 3 v 43 EP × 4). All patients were extubated immediately after the operation. None were reintubated or discharged on oxygen. Two patients in each cohort required an intensive care unit stay for nonpulmonary reasons. Patients treated with BEP required shorter use of supplemental oxygen (0.99 v 1.63 days; P = .005). No significant differences were found in preoperative mass size ( P = .42) or concomitant surgeries ( P = .58). Operative time was significantly shorter (131 v 170 minutes; P < .01), and estimated blood loss was considerably less (194 v 226 mL; P < .01) in patients treated with BEP. Length of stay was shorter in patients treated with BEP (3.3 v 3.9 days; P < .01). Conclusion In a modern surgical cohort, the inclusion of bleomycin does not seem to influence pulmonary morbidity, operative difficulty, or nonpulmonary postoperative complications after PC-RPLND in men with IGCCCG good-risk GST.

Prostate cancer is poorly visualized on ultrasonography (US) so that current biopsy requires either a templated technique or guidance after fusion of US with magnetic resonance imaging. Here we determined the ability for photoacoustic tomography (PAT) and US followed by texture-based image processing to identify prostate biopsy targets. K-means clustering feature learning and testing was performed on separate datasets comprised of 1064 and 1197 nm PAT and US images of intact, ex vivo human prostates. 1197 nm PAT was found to not contribute to the feature learning, and thus, only 1064 nm PAT and US images were used for final feature testing. Biopsy targets, determined by the tumor-assigned pixels’ center of mass, located 100% of the primary lesions and 67% of the secondary lesions. In conclusion, 1064 nm PAT and US texture-based feature analysis provided successful prostate biopsy targets. Keywords: Photoacoustic imaging, Prostate, Targeted biopsy, K-means clustering, Texture image processing

Patients with International Germ Cell Cancer Collaborative Group (IGCCCG) good-risk testicular cancer might receive either 4 cycles of etoposide and cisplatin (EP × 4) or 3 cycles of bleomycin, etoposide, and cisplatin (BEP × 3). We sought to examine differences in survival after retroperitoneal lymph node dissection (PC-RPLND) between patients who received EP × 4 compared with BEP × 3.The Indiana University Testis Cancer database was queried to identify IGCCCG good-risk PC-RPLND patients who received either EP × 4 or BEP × 3 induction chemotherapy. The primary outcome was overall survival (OS). Kaplan-Meier plots were generated for the EP × 4 and BEP × 3 groups and compared using the log rank test. Cox regression analysis was used to determine risk of mortality.A total of 223 patients met inclusion criteria between 1985 and 2011. Induction chemotherapy consisted of EP × 4 in 45 (20%) patients and BEP × 3 in 178 (80%). Most patients (78%) received their chemotherapy at outside institutions and were subsequently referred for PC-RPLND. The location of treating institution did not influence outcomes significantly when similar chemotherapy regimens were compared in this good-risk cohort. The 10-year OS for the EP × 4 and BEP × 3 groups were 91% and 98%, respectively (log rank P .01). The adjusted risk of death in the EP × 4 group showed a nonsignificant trend of 3 times greater compared with the BEP × 3 group (hazard ratio, 3.1; 95% confidence interval, 0.8-12.0; P = .10).The regimen of BEP × 3 resulted in a trend toward improved survival, however, this did not reach statistical significance. The location of treating institution seems less important in this risk group of patients.

Background To report our experience utilizing a multidisciplinary clinic (MDC) at Indiana University (IU) since the publication of the International Germ Cell Cancer Collaborative Group (IGCCCG), and to compare our overall survival (OS) to that of the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program. Patients and methods We conducted a retrospective analysis of all patients with metastatic germ-cell tumor (GCT) seen at IU from 1998 to 2014. A total of 1611 consecutive patients were identified, of whom 704 patients received an initial evaluation by our MDC (including medical oncology, pathology, urology and thoracic surgery) and started first-line chemotherapy at IU. These 704 patients were eligible for analysis. All patients in this cohort were treated with cisplatin–etoposide-based combination chemotherapy. We compared the progression-free survival (PFS) and OS of patients treated at IU with that of the published IGCCCG cohort. OS of the IU testis cancer primary cohort (n = 622) was further compared with the SEER data of 1283 patients labeled with ‘distant' disease. The Kaplan–Meier method was used to estimate PFS and OS. Results With a median follow-up of 4.4 years, patients with good, intermediate, and poor risk disease by IGCCCG criteria treated at IU had 5-year PFS of 90%, 84%, and 54% and 5-year OS of 97%, 92%, and 73%, respectively. The 5-year PFS for all patients in the IU cohort was 79% [95% confidence interval (CI) 76% to 82%]. The 5-year OS for the IU cohort was 90% (95% CI 87% to 92%). IU testis cohort had 5-year OS 94% (95% CI 91% to 96%) versus 75% (95% CI 73% to 78%) for the SEER ‘distant' cohort between 2000 and 2014, P-value Conclusion The MDC approach to GCT at high-volume cancer center associated with improved OS outcomes in this contemporary dataset. OS is significantly higher in the IU cohort compared with the IGCCCG and SEER ‘distant' cohort.

Surgery for metastatic testicular disease has been an essential factor in the long-term cure rates for men with testicular germ cell tumors. Robotic approaches to retroperitoneal lymph node dissection (R-RPLND) have been proposed as an alternative to open surgery with few if any adverse events reported. We report the clinical course for five recent patients referred to our center for recurrences after R-RPLND, focusing on recurrence patterns, treatment burden, and treatment-related morbidity and mortality. The median time to recurrence after R-RPLND was 259 d. The recurrence patterns after R-RPLND were aberrant from our past experience in managing recurrences after open RPLND. One man experienced an in-field recurrence located in close proximitry to an undivided lumbar vessel. Four patients had out-of-field recurrence in abnormal locations: pericolic space invading the sigmoid colon, peritoneal carcinomatosis with a perinephric mass, large-volume liver lesions with suprahilar disease extending into the retrocrural space, and lymph nodes in the celiac axis. The treatment burden was high: the five men were subjected to 12 different chemotherapy regimens and three underwent additional surgeries. Three patients developed significant cisplatin-induced toxicity. One patient died due to progression of testicular cancer after failing all chemotherapy and surgical options. Patient summary We report our initial experience in managing patients with testicular cancer referred to our institution after robotic retroperitoneal lymph node dissection (RPLND). We found that the recurrences were highly variable and in unusual locations and were associated with a high treatment burden. We conclude that further investigation into the safety and long-term oncologic efficacy of robotic RPLND is necessary before widespread implementation.

Introduction and Objective The management of severe symptoms secondary to radiation changes to the bladder can be difficult. Many patients often endure costly procedures, hospitalizations, transfusions, and physician visits for intractable symptoms. Our aim was to evaluate the short-term efficacy and feasibility of urinary diversion in patients with severe, debilitating symptoms related to radiation cystitis by focusing on perioperative data examining surgical feasibility and assess for any improvement in the number of procedures, transfusions, hospitalizations, and office visits required. Methods With IRB approval, we queried our institutional database for patients with a diagnosis code of radiation cystitis who underwent urinary diversion with or without bladder removal from 2011 to 2018. We reviewed institutional and regional record to assess pre, peri and postoperative outcomes, including rates of surgical procedures, hospitalizations, transfusions and clinic visits, in the year before and after treatment. Non-parametric statistics and linear regression were used. Results Of the 286 patients with radiation cystitis, 45 patients underwent definitive urinary diversion – 31 with concomitant cystectomy and 14 with diversion alone. Analysis of perioperative variables such as estimated blood loss, surgical time, post-operative hospital stay or complication rates were similar to our experience with cystectomy in non-radiated patients. With a mean follow up of 14.6 months, we found that the number of procedures, hospitalizations and transfusions objectively improved following radical surgery. Office visits, however, did not seem to be impacted by performing urinary diversion. There were no significant differences in post-operative benefits between patients that received a concomitant cystectomy and those that only underwent diversion. Conclusion Patients suffering from severe refractory symptomatic radiation cystitis may be best treated with a radical surgical approach. Definitive urinary diversion with or without cystectomy can lower burden of disease by reducing the need for additional procedures, hospitalizations, and blood transfusions on short term follow-up.

Following surgery for nonmetastatic renal cell carcinoma with tumor thrombus the risk of recurrence is significant but variable among patients. The purpose of this study was to develop and validate a predictive nomogram for individual estimation of recurrence risk following surgery for renal cell carcinoma with venous tumor thrombus.Comprehensive data were collected on patients with nonmetastatic renal cell carcinoma and thrombus treated at a total of 5 institutions from 2000 to 2013. Independent predictors of recurrent renal cell carcinoma from a competing risks analysis were developed into a nomogram. Predictive accuracy was compared between the development and validation cohorts, and between the nomogram and the UISS (UCLA Integrated Staging System, SSIGN (Stage, Size, Grade and Necrosis) and Sorbellini models.A total of 636 patients were analyzed, including the development cohort of 465 and the validation cohort of 171. Independent predictors, including tumor diameter, body mass index, preoperative hemoglobin less than the lower limit of normal, thrombus level, perinephric fat invasion and nonclear cell histology, were developed into a nomogram. Estimated 5-year recurrence-free survival was 49% overall. Five-year recurrence-free survival in patients with 0, 1, 2 and more than 2 risk factors was 77%, 53%, 47% and 20%, respectively. Predictive accuracy was similar in the development and validation cohorts (AUC 0.726 and 0.724, respectively). Predictive accuracy of the thrombus nomogram was higher than that of the UISS (AUC 0.726 vs 0.595, p = 0.001), SSIGN (AUC 0.713 vs 0.612, p = 0.04) and Sorbellini models (AUC 0.709 vs 0.638, p = 0.02).We present a predictive nomogram for postoperative recurrence in patients with nonmetastatic renal cell carcinoma with venous thrombus. Improving individual postoperative risk assessment may allow for better design and analysis of future adjuvant clinical trials.

Background Carcinoma in situ (CIS) is a poor prognostic finding in urothelial carcinoma. However, its significance in muscle-invasive urothelial carcinoma (MIUC) treated with neoadjuvant chemotherapy (NAC) is uncertain. We assessed the effect of CIS found in pretreatment transurethral resection of bladder tumor (TURBT) biopsies on the pathologic and clinical outcomes. Materials and Methods Subjects with MIUC treated with NAC before cystectomy were identified. The pathologic complete response (pCR) rates stratified by TURBT CIS status were compared. The secondary analyses included tumor response, progression-free survival (PFS), overall survival (OS), and an exploratory post hoc analysis of patients with pathologic CIS only (pTisN0) at cystectomy. Results A total of 137 patients with MIUC were identified. TURBT CIS was noted in 30.7% of the patients. The absence of TURBT CIS was associated with a significantly increased pCR rate (23.2% vs. 9.5%; odds ratio, 4.08; 95% confidence interval, 1.19-13.98; P = .025). Stage pTisN0 disease was observed in 19.0% of the TURBT CIS patients. TURBT CIS status did not significantly affect the PFS or OS outcomes. Post hoc analysis of the pTisN0 patients revealed prolonged median PFS (104.5 vs. 139.9 months; P = .055) and OS (104.5 vs. 152.3 months; P = .091) outcomes similar to those for the pCR patients. Conclusion The absence of CIS on pretreatment TURBT in patients with MIUC undergoing NAC was associated with increased pCR rates, with no observed differences in PFS or OS. Isolated CIS at cystectomy was frequently observed, with lengthy PFS and OS durations similar to those for pCR patients. Further studies aimed at understanding the biology and clinical effect of CIS in MIUC are warranted.

Partial nephrectomy (PN) reduces the risk of postoperative chronic renal insufficiency (CRI). However, some patients still develop CRI after PN, and may eventually require dialysis. Being able to predict renal function before PN helps in counseling patients and managing expectations. We aimed to construct nomograms that predict estimated glomerular filtration rates (eGFRs), defined by the modification of diet in renal disease (MDRD) and the chronic kidney disease epidemiology collaboration (CKD-EPI) formulae, at 1 year after PN, using only preoperative covariates as predictors.We identified patients who underwent PN in our institution between 2004 and 2016, with known postoperative serum creatinine levels at 1 year. The preoperative covariates included patients' demographics, chronic comorbid conditions, tumor characteristics, and preoperative renal status. The endpoints were eGFRs at 1 year after PN, calculated using the MDRD and the CKD-EPI formulae. We first identified preoperative covariates with significant associations with the endpoints by Pearson correlation and independent samples t-test. Suitable covariates were then included in two multivariate linear regression models, for constructing and internally validating two nomograms.461 patients were eligible for analysis. The percentage of patients with eGFR below 60 mL/min/1.73 mWe constructed and internally validated two nomograms to predict eGFRs at 1 year after PN, using only preoperative covariates as predictors.

Objective To update previously reported outcomes of modified-template post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) in appropriately selected patients with metastatic non-seminomatous germ cell tumour (NSGCT), as our previous report was criticised for short follow-up and so we now provide a long-term update on this cohort. Patients and methods In all, 100 patients with normal serum markers after cisplatin-based chemotherapy and residual retroperitoneal tumour underwent modified PC-RPLND between 1991 and 2004. Using a prospectively managed institutional testicular cancer database, long-term follow-up was obtained. Results As previously reported, 43 patients underwent a right-modified template, 18 patients underwent a full-left-modified template, and 39 patients underwent a left-modified template. The updated long-term median follow-up for the entire cohort is 125 months. Seven patients developed recurrent disease with a median (range) time to recurrence of 11 (6-102) months, and one patient died from recurrent disease in the chest 4 years after surgery. All recurrences were outside the boundaries of a full-bilateral template RPLND, with the most common location of recurrence being the chest. The 5- and 10-year recurrence-free survival rates were 93% and 92%, respectively. The overall survival at 10 years was 99%. Conclusions In appropriately selected patients with low-volume disease before and after chemotherapy, a modified template has durable long-term efficacy without risk of in-field recurrences at a median follow-up of 125 months.

Penile cancer is a rare neoplasm representing less than 1% of all malignancies in the USA and Europe but is a significant public health hazard in the developing world. Male neonatal circumcision has been associated with a dramatic decrease in penile cancer rates with countries such as Israel, where circumcision is widely performed, having the lowest incidence in the world at

INTRODUCTION AND OBJECTIVE:Late relapse (LR) following complete response to upfront radiation or chemotherapy for clinical stage II germ cell tumor is rare occurring in only 1-5% of cases. It is ch...

INTRODUCTION AND OBJECTIVE:Post-chemotherapy retroperitoneal lymph node dissections (PC-RPLND) for pure seminoma are widely considered to have an increased potential for surgical complexity and mor...

INTRODUCTION AND OBJECTIVES:The use of Alvimopan and multi-modality pain management in enhanced recovery after surgery (ERAS) protocols has improved outcomes after numerous surgical procedures. We ...