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.

Is percent seminoma associated with intraoperative morbidity during post-chemotherapy RPLND?

INTRODUCTION: To evaluate whether varying degrees of seminomatous elements in the primary orchiectomy specimen would be predictive of patient morbidity during post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) since the desmoplastic reaction with seminoma is associated with increased intraoperative complexity. MATERIALS AND METHODS: We retrospectively identified 127 patients who underwent PC-RPLND for residual retroperitoneal masses. Clinicodemographic, intraoperative, and 30 day postoperative outcomes were compared for patients with pure seminoma (SEM), mixed germ cell tumors (GCT) containing seminoma elements (NS+SEM), and tumors with no seminoma elements (NS). Multivariate logistic regression was used to determine independent predictors of intraoperative and postoperative 30 day complications. RESULTS: We excluded 19 patients who received chemotherapy prior to orchiectomy, 2 patients with primary extragonadal GCT, and 3 patients who underwent re-do RPLND, leaving 103 patients for analysis. Fourteen patients (13.6%) had SEM, 18 (17.5%) had NS+SEM, and 71 (68.9%) had only NS elements. SEM patients were older (p = 0.03), had more intraoperative blood loss (p = 0.03), and were more likely to have residual seminomatous components in their post-chemotherapy lymph node (LN) histology (p = 0.01). Percent seminoma in the orchiectomy specimen was an independent predictor of estimated blood loss > 1.5 liters (odds ratio: 1.04, 95% confidence interval: 1.01-1.07; p = 0.013) after adjusting for age, stage, IGCCC risk category, preop chemotherapy, number and largest LN removed, need for vascular or adjacent organ resection (including nephrectomy), and LN histology. CONCLUSIONS: Higher percentage of seminoma in the orchiectomy specimen is associated with increased estimated blood loss during PC-RPLND. Percent seminoma, therefore, may be a useful prognostic tool for appropriate pre-surgical planning prior to PC-RPLND.

Salvage focal prostate cryoablation for locally recurrent prostate cancer after radiotherapy: initial results from the cryo on-line data registry.

BACKGROUND: Several investigators have tried to apply salvage focal prostate cryoablation to small numbers of patients with biopsy-proven unilateral recurrent prostate cancer (PCa) after radiotherapy with the aim of decreasing complications of salvage cryoablation. We report contemporary outcomes of salvage focal cryoablation for locally recurrent PCa after radiotherapy within the Cryo On-Line Data (COLD) Registry. METHODS: We queried the COLD Registry to identify patients diagnosed as locally recurrent PCa after radiotherapy and treated with salvage focal cryoablation. Patients with hormone ablation after cryotherapy were excluded. The biochemical disease-free survival and morbidities were analyzed. Biochemical failure was defined using the Phoenix definition. RESULTS: From 2002 to 2012, 91 patients with biopsy-proven radio-recurrent PCa underwent salvage focal cryoablation with curative intent. The biochemical disease-free survival rates were 95.3%, 72.4%, and 46.5% at 1, 3, and 5 years, respectively. Positive biopsies after salvage focal cryoablation were observed in four of 14 patients who underwent biopsy (28.6%). Rectourethral fistula was observed in three cases (3.3%). Urinary retention was observed in six cases (6.6%). Incontinence (requiring pad use) was reported in five cases (5.5%). Intercourse was reported in 10 of 20 patients (50%) who reported potency before salvage focal cryoablation. CONCLUSIONS: The outcomes from this observational study indicate that salvage focal cryoablation can be an effective treatment with encouraging potency preservation for patients with locally recurrent PCa after radiotherapy. However, other morbidity including rectourethral fistula and incontinence are not clearly lower than for patients treated with salvage whole gland cryoablation. Studies with longer follow-up, more patients, and direct comparison to salvage whole gland cryoablation are needed before recommending salvage focal cryoablation as a standard treatment option for these patients.

Implications of Definitive Prostate Cancer Therapy on Soft Tissue Margins and Survival in Patients Undergoing Radical Cystectomy for Bladder Urothelial Cancer.

PURPOSE: We evaluated the possibility of an existing link between definitive prostate cancer treatment and its effect on positive soft tissue surgical margins at radical cystectomy. A secondary objective was to determine whether definitive prostate cancer treatment was associated with bladder cancer survival end points. MATERIALS AND METHODS: There were 749 patients who underwent radical cystectomy between 2000 and 2013. After excluding females and patients with nonurothelial histologies 561 men were identified, of whom 69 (12.3%) received single or multimodal definitive prostate cancer treatment. Univariate and multivariable logistic regression was used to determine an association between clinical and pathological features such as definitive prostate cancer treatment and positive soft tissue surgical margins. Cox regression models and competing risk regression were used to investigate the impact of definitive prostate cancer treatment and positive surgical margins on survival. RESULTS: The median age of the male population was 70.0 years. There were 57 cases of positive soft tissue surgical margins in our cohort of 561 men (10.2%). Of men who underwent previous definitive prostate cancer treatment 20 of 69 (29.0%) had positive surgical margins compared to 37 of 492 (7.5%) who never received definitive prostate cancer treatment (p <0.0001). Brachytherapy, radiotherapy, hormonal therapy and radical prostatectomy significantly increased the rate of positive margins. Brachytherapy (OR 5.8), radiotherapy (OR 2.7) and hormonal therapy (OR 5.1) remained independent predictors of positive margins on multivariate analysis. Positive margins were associated with negative effects on recurrence-free (HR 3.1), cancer specific (HR 4.1) and overall survival (HR 2.8). CONCLUSIONS: Patients with a history of definitive prostate cancer treatment are at increased risk for positive soft tissue surgical margins. Positive margins significantly impact bladder cancer recurrence-free, cancer specific and overall survival following radical cystectomy. Careful patient counseling and surgical planning are crucial when treating patients undergoing radical cystectomy who have a history of definitive prostate cancer treatment.

Patient and disease-specific factors and their influence on urinary reconstruction choice at a referral center.

PURPOSE: To evaluate potential socioeconomic and demographic factors that may influence or be associated with various types of urinary reconstruction (UR) following a radical cystectomy (RC) accounting for existing clinical variables. METHODS: There were 828 patients that underwent a RC and UR between 2000 and 2013. After excluding patients that did not meet medical or surgical criteria for a continent urinary reconstruction (CUR-orthotopic neobladder or continent catheterizable pouch), there were 714 patients available for analysis. Socioeconomic and demographic data along with disease-specific variables were recorded preoperatively and analyzed to determine a correlation with a particular type of UR. RESULTS: Non-continent urinary reconstruction (ileal conduit or cutaneous ureterostomies) and CUR accounted for 78.3 % (559/714) and 21.7 % (155/714) of UR following RC, respectively. On univariate analysis, younger age, marital status, employment status, type of insurance, ASA score, and preoperative glomerular filtration rate were significantly associated with CUR (p < 0.01). Travel distance, race, and education level were not factors for UR type. Additionally, there was no significant difference between males and females receiving a CUR. On multivariate analysis, older age [odds ratio (OR) 0.85, p < 0.01], marital status (OR 0.28, p < 0.01), insurance status (OR 0.22, p = 0.04), and higher ASA score (OR 0.50, p < 0.01) remained independent predictors of those less likely to receive a CUR. CONCLUSION: Predictable socioeconomic and demographic influences exist between the choice of UR after RC. Increasing age corresponds to a decreasing likelihood of receiving a CUR. No significant difference was seen between men and women in undergoing a CUR.

Robotic-Assisted Renal Surgery.

BACKGROUND: Minimally invasive surgical techniques have revolutionized the surgical management of kidney cancer. Current evidence suggests that the surgical developments gained by traditional laparoscopy have been advanced by the robotic platform, particularly as it has been applied to techniques for nephron preservation. METHODS: The medical literature from peer-reviewed journals was reviewed to evaluate the feasibility and efficacy of robotic-assisted surgery in the management of renal cell carcinoma. Particular attention was paid to studies comparing robotic-assisted surgery with more traditional surgical techniques. In this review, we have highlighted the evolution of robotic assistance for renal surgery as it pertains to renal oncology. The differing approaches to standard surgeries are discussed as well as current trends to improve perioperative outcomes.In addition, we have reviewed the application of robotic assistance to more complex cases and highlight technological advancements that have pushed the boundaries of surgical care. RESULTS: Robotic-assisted renal surgery is effective for appropriately selected patients. Robotic-assisted radical nephrectomy provides equivalent outcomes to traditional open and laparoscopic approaches, albeit with added financial burden. Robotic-assisted partial nephrectomy - through either transperitoneal or retroperitoneal access - can provide superior outcomes to laparoscopic approaches due to several technical advantages,including improved instrument articulation. CONCLUSIONS: Robotic assistance has transformed the delivery of surgical care to the patient with renal cell carcinoma. For renal surgery, morbidity and patient satisfaction are potentially improved when using robotic platforms compared with open and traditional laparoscopic approaches without compromising oncological control, and this is particularly true for nephron-sparing surgery.

Robotic-Assisted Radical Cystectomy.

BACKGROUND: The application and use of robotics during radical cystectomy for the treatment of bladder cancer are still being defined. METHODS: A systematic literature search was conducted, with an emphasis on studies published within the previous 5 years. Areas of interest included patient selection, outcomes, cost, and comparisons of robotic-assisted radical cystectomy to open surgery. RESULTS: Although data are lacking in this field, using robotic assistance for radical cystectomy may lead to improvements in estimated blood loss, time to bowel activity, and reduced hospital stay; however, these improvements come at the cost of increased operative time and have a learning curve. CONCLUSIONS: The widespread adoption of robotic-assisted radical cystectomy has not gained acceptance due to lack of evidence and clinical trials showing superiority over open surgery.

Robotic-Assisted Laparoscopic Radical Prostatectomy.

BACKGROUND: The use of radical prostatectomy for the treatment of prostate cancer has been increasing during the last decade partially due to the widespread adoption of the robotic-assisted laparoscopic technique. Although no prospective, randomized controlled trials have compared open radical prostatectomy (ORP) with robotic-assisted laparoscopic radical prostatectomy (RALRP), numerous comparative studies have been retrospectively conducted. METHODS: A systematic review of the literature was performed to clarify the role and advancement of RALRP. Studies comparing ORP with RALRP that measured outcomes of cancer control, urinary and sexual function, and complications were included. A nonsystematic review was utilized to describe the advancements in the techniques used for RALRP. RESULTS: RALRP is the procedure of choice when treating localized prostate cancer. This preference is due to the observed improvement in morbidity rates, as evidenced by decreased rates of blood loss and postoperative pain and similar oncological outcomes when compared with ORP. Robotic assistance during surgery is continually being modified and the techniques advanced, as evidenced by improved nerve sparing for preserving potency and reconstruction of the bladder neck to help in the early recovery of urinary continence. CONCLUSIONS: Morbidity rates should continue to improve with the advancement of minimally invasive techniques for radical prostatectomy. The adoption of robotic assistance during surgery will continue as the applications of robotic-assisted surgery expand into other solid organ malignancies.

Evidence to support that adventitial cysts, analogous to intraneural ganglion cysts, are also joint-connected.

Cystic adventitial disease (CAD) is a rare condition in which cyst is found within a vessel, typically producing symptoms of vascular compromise. Most commonly located in the popliteal artery near the knee, it has been reported in arteries and veins throughout the body. Its pathogenesis has been poorly understood and various surgical approaches have been recommended. We extrapolated some recent information about a similar condition, intraneural ganglion cyst affecting the deep fibular (peroneal) nerve, to the prototype, CAD of the popliteal artery. In intraneural ganglion cysts affecting the deep fibular nerve we have shown that an articular (neural) branch is the conduit between the superior tibiofibular joint and the main parent nerve for which epineurial dissection of joint fluid can occur. We hypothesized that the same principles would apply to CAD and that an articular (vascular) branch would be the conduit from the knee joint leading to dissection to the main parent vessel. We reviewed five patients with CAD of the popliteal artery in whom MRIs were available: two treated by the primary author well familiar with the proposed articular theory, and three treated by others at our institution, less familiar with it. We then reviewed the literature critically to assess for additional evidence to support our articular (synovial) theory and an anatomic explanation. In the two cases treated by the primary author a joint connection was identified on high resolution MRI prospectively and intraoperatively through the middle genicular artery (MGA); postoperatively in these cases there was no recurrence. In the other three cases, a joint connection was not identified on imaging or at operation. Reinterpretation of these cases revealed a joint connection through the MGA in the one patient who had preoperative imaging and subclinical persistence/recurrence in the two patients who underwent postoperative MRIs done for other reasons. Our review of the literature and imaging studies revealed unrecognized joint connections in CAD to the knee and other joints as well as evidence that the MGA is the conduit in cases of CAD of the popliteal artery. We believe that adventitial cysts originate in neighboring joints and dissect within articular (vascular) branches. In our opinion, the unifying articular theory and the principles introduced for intraneural ganglion cysts apply equally to common and rare sites of adventitial cysts.

Circulating tumor DNA based minimal residual disease detection and adjuvant treatment decision-making for muscle-invasive bladder cancer guided by modern clinical trials.

Up to 430,000 cases of bladder cancer are diagnosed each year worldwide. A proposed method for non-invasive monitoring has been to utilize a "liquid biopsy." Liquid biopsy has been proposed as a non-invasive method of testing biomarkers in bodily fluids in order to detect and survey cancer. The liquid biopsy could be utilized to obtain information regarding circulating tumor cells, circulating cell-free tumor DNA, circulating cell-free tumor RNA, and more. It is currently being investigated to help guide adjuvant therapy and improve oncological outcomes. We highlight an array of exciting past and ongoing clinical trials regarding ctDNA and adjuvant therapy in regard to urothelial carcinoma which we believe to be amongst the leaders in the field.

Ureteral calculi detection using low dose computerized tomography protocols is compromised in overweight and underweight patients.

PURPOSE: Low dose computerized tomography protocols have demonstrated a reduction in radiation exposure while maintaining excellent sensitivity and specificity in the detection of stones in patients of average size. Low dose computerized tomography protocols have not yet been evaluated in subjects in the extremes of weight. We evaluated the effect of body weight when using low dose protocols to detect ureteral calculi. MATERIALS AND METHODS: Three cadavers of increasing weight (55, 85 and 115 kg) were prepared by inserting 721 calcium oxalate stones (range 3 to 7 mm) in 33 random configurations into urinary tracts. Cadavers were then scanned using a GE LightSpeed® at 7 radiation settings. An independent, blinded review by a radiologist was conducted to generate ROC curves, with areas under the curve compared using a 1-way ANOVA (α = 0.05). RESULTS: Sensitivity and specificity were significantly lower in the low and high weight cadavers compared to the medium weight cadaver at 5 mAs (p <0.001) and 7.5 mAs (p = 0.048). Differences in sensitivity and specificity at radiation settings of 15 mAs or greater were not significant. CONCLUSIONS: The sensitivity and specificity for the detection of ureteral calculi on computerized tomography were decreased for underweight and overweight subjects when using extremely low dose radiation settings (less than 1 mSv). Low dose protocols of 15 mAs (2 mSv) can still be used for these subjects without jeopardizing the ability to identify ureteral stones.

Prostate specific antigen levels and prostate cancer detection rates in patients with end stage renal disease.

PURPOSE: Patients with end stage renal disease plus prostate cancer are ineligible to receive a renal transplant at most centers until an acceptable cancer-free period is demonstrated. To our knowledge previously established prostate specific antigen reference ranges have not been validated in patients with end stage renal disease. We determined age stratified 95th percentile prostate specific antigen reference ranges and the prostate cancer detection rate at specific prostate specific antigen intervals for patients with end stage renal disease. MATERIALS AND METHODS: We retrospectively reviewed the records of 775 male patients with end stage renal disease on the waiting list for a renal transplant who had undergone a serum prostate specific antigen test. Prostate specific antigen was stratified by age at the time of the blood test and 95th percentile reference ranges were calculated for each decade. A total of 80 patients underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination. The cancer detection rate was calculated for specific prostate specific antigen reference ranges. RESULTS: The age specific 95th percentile prostate specific antigen references ranges were 0 to 4.0 ng/ml for ages 40 to 49 in 137 patients, 0 to 5.3 ng/ml for ages 50 to 59 in 257, 0 to 10.5 ng/ml for ages 60 to 69 in 265 and 0 to 16.6 ng/ml for ages 70 to 79 years in 69. The cancer detection rate was 44%, 38% and 67% for prostate specific antigen 2.5 to 4.0, 4 to 10 and greater than 10 ng/ml, respectively. CONCLUSIONS: In our study population of patients with end stage renal disease age stratified prostate specific antigen was higher than in the general population. The cancer detection rate was increased in our patients with end stage renal disease compared to that in patients with normal renal function at specific prostate specific antigen intervals. Lower prostate specific antigen cutoffs may be appropriate to recommend prostate biopsy in patients with end stage renal disease.

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.

Advancing Precision Equity With Multicancer Detection Liquid Biopsies.

This Viewpoint discusses the clinical and socioeconomic potential of multicancer detection liquid biopsies.

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.

Predictors of Postoperative Complications in Patients Who Undergo Radical Nephrectomy and IVC Thrombectomy: A Large Contemporary Tertiary Center Analysis.

UNLABELLED: In an analysis of a large single-institution experience in the surgical management of renal cell carcinoma (RCC) and inferior vena cava (IVC) thrombus, the authors present the effect of RCC characteristics on survival, and aim to identify potential preoperative variables predictive of intraoperative complexity with regard to estimated blood loss, transfusion volume, surgical time, length of stay, and postoperative complication rates. Age, American Society of Anesthesiologists score, Charlson Comorbidity Index, preoperative calcium, preoperative creatinine, and IVC wall invasion were significantly related to complication rates. INTRODUCTION: Preoperative laboratory values are commonly used as markers of health and potential disease burden, however, their effect on perioperative complexity has not previously been assessed. The authors aimed to evaluate the effect of renal cell carcinoma and inferior vena cava (IVC) thrombus characteristics on cancer-specific survival (CSS), and identify potential preoperative variables predictive of intraoperative complexity. MATERIALS AND METHODS: In a retrospective chart review we identified 144 patients who underwent nephrectomy and IVC thrombectomy. Univariate and multivariate analyses were used to assess the effect of disease characteristics on CSS and postoperative complications. Linear regression analysis was used to determine the association between preoperative laboratory values and intraoperative complexity characterized by estimated blood loss (EBL), transfusion volume (TV), operative time, and length of hospital stay (LOS). RESULTS: Analysis of intraoperative complexity revealed a significant correlation between preoperative creatinine (Cr) and EBL (P = .022), TV (P = .041), and LOS (P = .005), and preoperative hemoglobin (Hgb) was associated with increased EBL (P < .001) and TV (P < .001). Multivariate analyses showed a significant relationship between overall complication rates and preoperative calcium (Ca; P = .012), American Society of Anesthesiologists (ASA) score (P = .003), and IVC wall invasion (P = .005), and a significant association between major complications and preoperative Ca (P = .011), preoperative Cr (P = .041), age (P = .050), and Charlson Comorbidity Index (CCI; P = .002). CONCLUSION: With regard to intraoperative complexity and postoperative complications, preoperative Cr and Hgb were significantly associated with increased EBL, TV, and LOS, and ASA score, preoperative Ca, preoperative Cr, IVC wall invasion, age, and CCI were found to have significant relationships with complication rates.

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.

Disparities in Interpretation of Primary Testicular Germ Cell Tumor Pathology.

OBJECTIVES: Accurate pathologic interpretation of testicular germ cell tumors (GCTs) can be problematic due to low incidence and variation in histologic patterns. By analyzing changes in the diagnosis of testicular specimens after secondary review, we hoped to determine how these can affect prognosis and treatment. METHODS: From 1999 to 2013, a total of 235 patients underwent radical orchiectomy at a referring facility and had pathology specimens reanalyzed by our center's pathologists with expertise in genitourinary malignancies. We identified discrepancies in pathologic reporting. RESULTS: Fifty (21.3%) patients had variations in interpretation of their orchiectomy specimens. A clinically significant alteration was identified in 16 (6.8%) patients, most commonly due to recognition (or misrecognition) of lymphovascular invasion (LVI) associated with nonseminomatous germ cell tumors (NSGCTs). Changes in LVI status resulted in upstaging or downstaging from clinical stage 1A to stage 1B or vice versa in six patients with NSGCTs, with a subsequent change in therapeutic strategy. In addition, one patient with stage 1 pure seminoma had been misclassified with nonseminoma. CONCLUSIONS: Inaccurate interpretation of orchiectomy specimens is not uncommon and may lead to incorrect tumor staging, imprecise assignment of progression risk, and inappropriate management recommendations. Secondary opinions of primary GCT orchiectomy specimens potentially facilitate appropriate counseling and therapeutic strategies.

Novel targeted therapies for the treatment of penile cancer.

INTRODUCTION: The treatment of penile cancer has changed over the past decade in that it was primarily a surgically managed disease and those with locally advanced or metastatic disease uniformly had a very poor prognosis. However, with the use of better traditional systemic chemotherapeutic agents in the neoadjuvant and adjuvant settings, the disease-specific survival and general outlook has improved. However, there is still a large group of patients who will progress even while on systemic therapy. It is in those patients where the application of targeted therapies has been investigated with some experiencing partial or even complete responses. With the improvement seen in patients with chemotherapy refractory disease, the application of novel targeted agents in the neoadjuvant setting may have a resultant positive impact on patient survival. AREAS COVERED: This review includes research pertaining to targeted therapies, biomarkers and signaling pathways involved with penile cancer. The article was based on a literature search using the keywords 'penile cancer' and 'targeted therapies'. EXPERT OPINION: Penile cancer at the advanced stages of the disease has a high mortality. The utilization of novel targeted therapies in these situations is warranted in combination with, or sequentially with, traditional cytotoxic chemotherapy to improve the patient survival rate. Personalized therapy is nearly here for penile cancer and should be made real within the next decade.

Hybrid transureteral nephrectomy in a survival porcine model.

BACKGROUND AND OBJECTIVES: Natural-orifice approaches for nephrectomy have included access via the stomach, vagina, bladder, and rectum. Recently, the feasibility of using the ureter as a natural orifice for natural-orifice transluminal endoscopic surgery nephrectomy has been demonstrated in a nonsurvival porcine model. The purpose of this study was to assess the outcomes of transureteral laparoscopic natural-orifice transluminal endoscopic surgery nephrectomy in a survival porcine model. METHODS: Three pigs underwent hybrid transureteral natural-orifice transluminal endoscopic surgery nephrectomy. An experimental balloon/dilating sheath was inserted over a wire to dilate the urethra, ureteral orifice, and ureter. Through a bariatric 12-mm laparoscopic port, the ureter was opened medially and the hilar dissection was performed. Next, 2 needlescopic ports were placed transabdominally to facilitate hilar transection. The kidney was morcellated using a bipolar sealing device and extracted via the ureter using the housing of a bariatric stapling device. The ureteral orifice was closed with a laparoscopic suturing device. The bladder was drained by a catheter for 10 to 14 days postoperatively. Pigs were euthanized on postoperative day 21. RESULTS: All surgical procedures were successfully completed, with no intraoperative complications. One pig had an episode of postoperative clot retention that resolved with catheter irrigation. Each pig was healthy and eating a normal diet prior to euthanasia. CONCLUSIONS: This study demonstrates the feasibility of a hybrid transureteral approach to nephrectomy in a survival porcine model. This technique avoids the intentional violation of a second organ system and the risk for peritoneal contamination. Improved instrumentation is needed prior to implementation in the human population.