Impact of the MyProstateScore (MPS) Test on the Clinical Decision to Undergo Prostate Biopsy: Results From a Contemporary Academic Practice.

OBJECTIVE: To evaluate the association of the MyProstateScore (MPS) urine test on the decision to undergo biopsy in men referred for prostate biopsy in urology practice. METHODS: MPS testing was offered as an alternative to immediate biopsy in men referred to the University of Michigan for prostate biopsy from October 2013 through October 2016. The primary endpoint was the decision to perform biopsy. The proportion of patients undergoing biopsy was compared to predicted risk scores from the Prostate Cancer Prevention Trial risk calculator (PCPTrc). Analyses were stratified by the use of multiparametric magnetic resonance imaging (mpMRI). The associations of PCPTrc, MPS, and mpMRI with the decision to undergo biopsy were explored in a multivariable logistic regression model. RESULTS: Of 248 patients, 134 (54%) proceeded to prostate biopsy. MPS was significantly higher in biopsied patients (median 29 vs14, P < .001). The use of biopsy was strongly associated with MPS, with biopsy rates of 26%, 38%, 58%, 90%, and 85% in the first through fifth quintiles, respectively (P < .001). MPS association with biopsy persisted upon stratification by mpMRI. On multivariable analysis, MPS was strongly associated with the decision to undergo biopsy when modeled as both a continuous (odds ratio [OR] 1.05, 95%; confidence interval [CI] 1.04-1.08; <.001) and binary (OR 7.76, 95%; CI 4.14-14.5; P < .001) variable. CONCLUSION: Many patients (46%) undergoing clinical MPS testing as an alternative to immediate prostate biopsy were able to avoid biopsy. Increasing MPS was strongly associated with biopsy rates. These findings were robust to use of mpMRI.

Urinary markers aiding in the detection and risk stratification of prostate cancer.

The purpose of this review is to highlight the role of existing and promising urinary biomarkers for the detection and prognostication of prostate cancer (PCa). A number of novel urinary biomarkers have been introduced into the clinical space, which in combination with clinical variables, have demonstrated an increased ability to select patients for biopsy and identify men at risk of harboring clinically significant PCa. Though a number of assays require further validation, initial data is promising and forthcoming results will ultimately determine their clinical utility and commercial availability. For the past 30 years, first-line screening for PCa has relied on measurement of serum prostate-specific antigen (PSA) levels and the results from a digital rectal exam (DRE). A large body of evidence from the last 3 decades indicates that these screening methods are problematic, and often inadequate for detecting clinically significant PCa. Extensive efforts have recently been made to identify and commercialize novel PCa biomarkers for more effective detection of PCa, either alone or in combination with current screening methods. This review article highlights problems with current screening standards, and discusses 6 urinary biomarker assays in terms of their ability to detect and risk-stratify PCa: prostate cancer antigen 3 (PCA3), TMPRSS2-ERG, second chromosome locus associated with prostate-1 (SChLAP1), ExoDx, SelectMDx, and Michigan Prostate Score (MiPS).

Multi-institutional Survival Analysis of Incidental Pathologic T3a Upstaging in Clinical T1 Renal Cell Carcinoma Following Partial Nephrectomy.

OBJECTIVE: To evaluate whether incidental pathologic T3a (pT3a) upstaging after partial nephrectomy (PN) for clinical T1 disease results in inferior oncologic outcomes compared to pT1a-b disease. MATERIALS AND METHODS: Retrospective chart review was completed at the University of Michigan and Moffitt Cancer Center to identify patients undergoing PN for clinical T1 masses between 1995 and 2015. A total of 1955 patients were identified, of which 95 had pT3a upstaging. Median follow-up was 38.2 months. Patients with pT3a disease were individually matched by clinicopathologic features with patients undergoing PN with pT1a-b disease in a 1:2 ratio. Kaplan-Meier analysis and univariate and multivariable Cox proportional hazards regression analysis were performed. Primary endpoint was recurrence-free survival (RFS). Secondary endpoints were all-cause mortality, cancer-specific survival (CSS), and rates of local and distant recurrence. RESULTS: Recurrence rates were significantly higher in pT3a disease compared to pT1a-b controls (P <.01). In those patients with pT3a upstaging, 3- and 5-year RFS were 81% and 58%, compared to 86% and 75% in pT1a-b controls (P = .01). CSS at 3 and 5 years were 91% and 90% in pT3a disease and 100% and 97% in pT1a-b controls (P <.01). All-cause mortality at 3 and 5 years were 82% and 71% in pT3a disease and 93% and 80% in pT1a-b controls (P = .04). Univariate and multivariable analysis of pT3a disease demonstrated no association between demographic or pathologic characteristics and RCC recurrence. CONCLUSION: Patients with pT3a upstaging following PN experience a significantly reduced RFS and CSS when compared to pT1 disease.

Using Imaging to Predict Treatment Response in Genitourinary Malignancies.

CONTEXT: Over the previous2 decades, there have been numerous advancements in the diagnostic evaluation, therapeutic management, and postoperative assessment of genitourinary malignancies. OBJECTIVE: To present a review of current and novel imaging modalities and their utility in the assessment of therapeutic response in the systemic management of renal, testicular, and prostate cancers. EVIDENCE ACQUISITION: A PubMed/Medline search of the current published literature inclusive of prospective and retrospective original research, systematic reviews, and meta-analyses was conducted evaluating imaging modalities for renal cell carcinoma, prostate cancer, and testicular cancer. All relevant literature was individually reviewed and summarized to provide a concise description of the currently available imaging modalities and their efficacy in assessing treatment response of the genitourinary malignancies targeted in this review. EVIDENCE SYNTHESIS: Conventional imaging techniques play a pivotal role in predicting the treatment response of genitourinary malignancies and have, therefore, been incorporated into clinical guidelines. Advancements in imaging technology have led to increased utilization for prognostication of a genitourinary cancer's response to therapy. CONCLUSIONS: A good understanding of current recommended imaging techniques to evaluate treatment response in genitourinary malignancies is of paramount importance for today's clinician, who faces increasing treatment modalities. PATIENT SUMMARY: In this review, we summarize available imaging modalities in the evaluation of treatment response in kidney, prostate, or testicular tumors. We believe that a good understanding of current imaging modalities is of paramount importance for healthcare providers treating these cancers.

Robotic-assisted Thoracoscopic Transdiaphragmatic Adrenalectomy (RATTA) for Metastatic Renal Cell Carcinoma.

OBJECTIVE: Robotic-assisted thoracoscopic transdiaphragmatic adrenalectomy (RATTA) represents a novel surgical approach for the management of adrenal pathology in patients with a history of extensive transperitoneal or retroperitoneal procedures. METHODS: Here we report the first described case of RATTA in a 56-year-old woman with metastatic renal cell carcinoma to the left adrenal gland and right lung. With the assistance of cardiothoracic surgery, this patient underwent robotic-assisted thoracoscopic pulmonary wedge resection and RATTA. In brief, after completion of the pulmonary wedge resection by thoracic surgery the diaphragm was incised starting at the left crus and extending laterally through the diaphragmatic muscle, exposing the retroperitoneal space and fat. The adrenal gland with mass was identified, dissected from surrounding structures, and extracted. The diaphragm was then closed using Ethibond suture with polytetrafluoroethylene felt pledgets. A 22-Fr chest tube was placed in the thoracic cavity. RESULTS: Operative and postoperative courses were uncomplicated. The patient was discharged on postoperative day 4. Pathology confirmed metastatic clear cell renal cell carcinoma in both the left adrenal and the right lung nodules with negative surgical margins. CONCLUSION: The case described here highlights the surgical technique and ideal patient population in which RATTA serves as a feasible and safe alternative to conventional laparoscopic approaches in the treatment of adrenal pathologies.

Minimally Invasive Inguinal Lymphadenectomy in the Management of Penile Carcinoma.

OBJECTIVE: To report and analyze the outcomes of endoscopic inguinal lymph node dissection (E-ILND), inclusive of video endoscopic ILND (VEIL) and robotic-assisted ILND (RAIL) approaches, in the largest reported series to date. MATERIALS AND METHODS: We retrospectively identified men with penile cancer who underwent E-ILND. Nodal resection volume, perioperative parameters, and postoperative complications were assessed and analyzed. A subset analysis of complications by tumor and operative characteristics was performed to determine the impact of these variables on complication rates. RESULTS: A total of 34 E-ILND, comprising 7 VEIL and 27 RAIL limbs, were performed. Median nodal yield was 10.0 (interquartile range [IQR] 6.0-12.5) in all E-ILND limbs and 8.0 (IQR 13.0-23.0) in RAIL limbs. Median length of stay was 1 day (range 1-3) following E-ILND and RAIL procedures. The saphenous vein was spared in 57% (4/7) of VEIL and 100% (27/27) of RAIL limbs. Postoperative complications occurred in 33% (6/18) of E-ILND, including 21% (3/14) of RAIL patients. Median follow-up was 5.5 months (IQR 3.0-10.8), during which time 3 patients developed regional or distant metastases at a median duration of 1.7 months (IQR 0.9-3.9). CONCLUSION: E-ILND is feasible from a technical standpoint, and our results demonstrate that lymph node counts are comparable with an open approach. Importantly, E-ILND has the potential to reduce complication rates and time to convalescence when compared with open ILND.

The Role of Transurethral Resection in Trimodal Therapy for Muscle-Invasive Bladder Cancer.

While radical cystectomy (RC) with pelvic lymph node dissection (PLND) represents the accepted gold standard for the treatment of muscle-invasive bladder cancer, this treatment approach is associated with significant morbidity. As such, bladder preservation strategies are often utilized in patients who are either deemed medically unfit due to significant comorbidities or whom decline management with RC and PLND secondary to its associated morbidity. In a select group of patients, meeting strict criteria, bladder preservation approaches may be employed with curative intent. Trimodal therapy, consisting of complete transurethral resection of bladder tumor (TURBT), chemotherapy, and radiation therapy has demonstrated durable oncologic control and long-term survival in a number of studies. The review presented here provides a description of trimodal therapy and the role of TURBT in bladder preservation for patients with muscle-invasive bladder cancer.

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.

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.

Oncological control associated with surgical resection of isolated retroperitoneal lymph node recurrence of renal cell carcinoma.

OBJECTIVE: To evaluate the outcome of patients after surgical resection of isolated retroperitoneal lymph node (RPLN) recurrence of renal cell carcinoma (RCC) using a multicentre international cohort. PATIENTS AND METHODS: In all, 50 patients were identified who underwent resection of isolated RPLN recurrence of RCC at four institutions after nephrectomy for pTany Nany M0 disease. Progression-free (PFS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were used to assess the association of clinicopathological characteristics with disease progression. RESULTS: The median (interquartile range, IQR) age at resection was 57.0 (50.0-62.5) years. The median (IQR) time to RPLN recurrence after nephrectomy was 12.6 (6.9-39.5) months, with no significant difference in median time to RPLN recurrence between patients with N+ disease at nephrectomy (10.7 [6.5-24.6] months) and those with Nx/pN0 disease at nephrectomy (13.7 [8.7-44.2] months) (P = 0.66). The median (IQR) size of the RPLN recurrence before resection was 2.6 (1.9-5) cm. The most common site for RPLN recurrence was within the interaortocaval region (34%). The median (IQR) follow-up after RPLN resection for patients alive at last follow-up was 28.0 (13.7-51.2) months. During follow-up, 26 patients developed RCC recurrence, at a median (IQR) of 9.9 (4.0-18.5) months after RPLN resection. Of those who developed a secondary recurrence, disease was again isolated to the retroperitoneum in seven patients. In all, 11 patients subsequently died, including 10 who died from disease. The median PFS after RPLN resection was 19.5 months, with a 3- and 5-year PFS of 40.5% and 35.4%, respectively. We also found that RPLN recurrence at ≤12 months after nephrectomy was associated with a significantly inferior median PFS (12.3 months) compared with RPLN recurrence at >12 months after nephrectomy (47.6 months; P = 0.003). Moreover, on multivariate analysis, a shorter time to recurrence remained associated with a significantly increased risk for subsequent disease progression (hazard ratio 3.51; P = 0.005). CONCLUSION: Surgical resection of isolated RPLN recurrence from RCC may result in durable cancer control in appropriately selected patients. Recurrence at ≤12 months after nephrectomy was associated with a significantly increased risk of progression after resection, underscoring the importance of this variable for risk stratification. Thus, we recommend that, in the setting of isolated RPLN recurrence of RCC (in patients without precluding comorbidities), careful consideration with the patients and medical oncology colleagues be undertaken about the relative and individualised benefits of surgical resection, systemic therapy, and surveillance.

Perivascular epithelioid cell tumor (PEComa) of the urinary bladder associated with Xp11 translocation.

Perivascular epithelioid cell-containing tumors (PEComas) represent a rare family of neoplasms. Their dichotomous phenotypic features, including both myogenic and mylanocytic features, can make a definitive diagnosis difficult. Such tumors have been associated with the overexpression of transcription factor E3 (TFE3). An Xp11 translocation could account for the aberrant activity of TFE3 but has never before been described in affiliation with a PEComa of the urinary bladder. While PEComas of the bladder have exhibited benign clinical courses to date, here we present an intravesical PEComa shown to have an Xp11 translocation and resultant overexpression of TFE3, indicating an aggressive, metastatic nature. No consistent tumor characteristics have proven accurate at identifying aggressive tumors. However, mTOR inhibitors offer a mechanistic management strategy when systemic therapy is warranted.

Surgical outcomes in the management of isolated nodal recurrences: a multicenter, international retrospective cohort.

PURPOSE: We report a multicenter international cohort representing what is to our knowledge the largest surgical experience with managing isolated retroperitoneal nodal recurrence of renal cell carcinoma, a unique subset of locoregional disease, yet to be described in detail. MATERIALS AND METHODS: Patients with isolated nodal recurrence of pTanyN+M0 disease after nephrectomy were identified by retrospective chart review at 3 independent institutions. Progression-free survival was estimated by the Kaplan-Meier method and used to compare survival outcomes between primary T(1-2)N(any)M0 and T3N(any)M0 tumors as well as clear cell and nonclear cell histology renal cell carcinoma. RESULTS: A total of 22 patients met study inclusion criteria. Median time to local postoperative recurrence was 31.5 months (IQR 12.9-43.3). After resection of isolated nodal recurrence 10 patients (46%) had a secondary recurrence at a median of 11.2 months (IQR 8.1-18.4), of whom 2 (9%) died of the disease. Overall median progression-free survival was 12.7 months, including 24.8 months for T(1-2)N(any)M0 tumors, 9.9 months for T3N(any)M0 tumors, and 13.4 and 17.6 months for clear and nonclear cell renal cell carcinoma, respectively. CONCLUSIONS: Surgical resection represents the best curative option for patients who present with isolated retroperitoneal lymph node recurrence of renal cell carcinoma. Durable postoperative progression-free survival is attainable in many patients regardless of histology or clinical TNM stage. In addition, our cohort showed a lower renal cell carcinoma related mortality rate than in previous series of local metastasis. As such, all patients free of precluding comorbidities should be considered candidates for complete surgical resection performed by an experienced genitourinary surgeon.