Surveillance after Complete Response to First-Line Chemotherapy in Patients with Metastatic Nonseminomatous Germ Cell Tumor.

PURPOSE: The optimal management of patients with metastatic germ cell tumors who achieve a complete response (CR) after first-line chemotherapy remains unsettled. This study reports long-term outcomes of patients with metastatic germ cell tumor managed with surveillance after achieving a CR to first-line chemotherapy. MATERIALS AND METHODS: Patients with metastatic nonseminomatous germ cell tumor treated at Indiana University between 1990 and 2017 who achieved a CR after first-line chemotherapy and were monitored with surveillance were retrospectively analyzed. CR was defined as normalization of tumor markers AFP and hCG, and no residual mass >1 cm in long axis. Kaplan-Meier methods were used to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: Three hundred sixty-seven patients achieved a CR and were managed with surveillance. After a median followup of 4.97 years, 34 patients had disease progression. At most recent followup, 346 (94%) patients were alive with no evidence of disease, 10 patients (2.7%) died of their disease, 5 (1.4%) died of other causes and 6 (1.6%) were lost to followup. The estimated 2-year PFS was 91% (95% CI: 87%-94%) and 2-year OS was 98% (95% CI: 96%-99%). The estimated 2-year PFS by International Germ Cell Cancer Collaborative Group risk category was 92% for good vs 90% for intermediate vs 87% for poor risk (p=0.15), and the estimated 2-year OS was 99% for good vs 96% for intermediate vs 93% for poor risk disease (p=0.001). CONCLUSIONS: Patients with metastatic nonseminomatous germ cell tumor who achieve a CR after first-line chemotherapy can be observed. Most patients who relapse can be salvaged with surgery and/or chemotherapy.

Association of Lymph Node Count and Survival after Primary Retroperitoneal Lymphadenectomy for Nonseminomatous Testicular Cancer.

PURPOSE: Retroperitoneal lymph node dissection (RPLND) for men with clinical stage (CS) I or II testicular nonseminomatous germ cell tumor (NSGCT) has both staging and therapeutic implications. We aimed to investigate the impact of lymph node count (LNC) on outcome after primary RPLND for men with CS I or II NSGCT using a nationally representative data set. MATERIALS AND METHODS: A retrospective analysis of men who received a primary RPLND for CS I or II NSGCT was performed using the National Cancer Database. The Kaplan-Meier method was used to determine overall survival (OS) according to LNC. Logistic regression analyses were used to identify factors associated with LNC >20 and factors predictive of lymph node-positive (pN+) disease after primary RPLND. RESULTS: Of 1,376 men who comprised our analytical cohort, 50.1% and 49.9% had 1-20 lymph nodes (LNs) and >20 LNs removed, respectively. Five-year OS rates were 96.4% and 99.1% for men with 1-20 and >20 LNs resected, respectively (p=0.004). A higher proportion of men with >20 LNs removed were treated at academic centers, had private insurance, presented with higher AJCC (American Joint Committee on Cancer) CS and were more likely to have pN+ disease, compared to those with 1-20 LNs removed. Factors significantly associated with pN+ disease after RPLND include higher AJCC CS and LNC (per 10-count increase). CONCLUSIONS: Higher LNC after primary RPLND significantly increases the likelihood of identifying pN+ disease and is associated with improved OS. Our data support the therapeutic implications of a thoroughly performed RPLND in the primary setting.

Surgical Management of Retrocrural Disease in Germ Cell Tumors: Outcomes and Evolution of Practice.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Percentage of Teratoma in Orchiectomy and Risk of Retroperitoneal Teratoma at the Time of Postchemotherapy Retroperitoneal Lymph Node Dissection in Germ Cell Tumors.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: A total of 422 men were included. Presence of teratoma in the orchiectomy (OR 1.02, p <0.001), residual mass size (OR 1.16, p <0.001) 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. CONCLUSIONS: 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.

Long-Term Oncologic Outcomes after Primary Retroperitoneal Lymph Node Dissection: Minimizing the Need for Adjuvant Chemotherapy.

PURPOSE: We analyzed the oncologic outcomes of men undergoing primary retroperitoneal lymph node dissection and characterized the use of adjuvant chemotherapy and template dissections. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Delaying Cancer Cases in Urology during COVID-19: Review of the Literature.

PURPOSE: 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. MATERIALS AND METHODS: We reviewed published literature on bladder cancer, upper tract urothelial carcinoma, penile cancer, testis cancer, prostate cancer, renal cancer and adrenal cancer. RESULTS: 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. CONCLUSIONS: This review should further assist urologists in recognizing patients with potentially aggressive tumor biology that warrants early treatment.

A Prospective Program to Reduce the Clinical Incidence of Clostridium difficile Colitis Infection after Cystectomy.

PURPOSE: The development of Clostridium difficile infection after cystectomy is associated with significant morbidity and mortality. We implemented a prospective screening program to identify asymptomatic carriers of C. difficile and assessed its impact on clinical C. difficile infection rates compared to historical matched controls. MATERIALS AND METHODS: Prospective C. difficile screening prior to cystectomy began in March 2015. The 380 consecutive patients who underwent cystectomy before the initiation of screening (control cohort) were matched based on 5 clinical factors with the 386 patients who underwent cystectomy from March 2015 to December 2017 (trial cohort). Patients who screened positive were placed in contact isolation and treated prophylactically with metronidazole. Multivariable models were built on an intent to screen basis and an effectiveness of screening basis to determine whether screening reduced the rate of symptomatic C. difficile infection postoperatively. RESULTS: With the implementation of the screening protocol the C. difficile infection rate declined from 9.4% to 5.5% (OR 0.52, p = 0.0268) in patients on the intent to screen protocol and from 9.2% to 4.9% in those on the effectiveness of screening protocol (OR 0.46, p = 0.0174). CONCLUSIONS: C. difficile screening prior to cystectomy is associated with a significant decrease in the rate of clinically symptomatic infection postoperatively. These results should be confirmed in a randomized controlled trial.

Diagnosis and Treatment of Early Stage Testicular Cancer: AUA Guideline.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Penile cancer epidemiology and risk factors: a contemporary review.

PURPOSE OF REVIEW: Our objective is to present an overview of epidemiologic, clinical, and molecular risk factors with a focus on contemporary literature. RECENT FINDINGS: Penile cancer is a rare and aggressive neoplasm that accounts for less than 1% of male malignancies in the United States. Geographical disparities in incidence of disease are evident with high rates concentrated in the developing world (2.8-6.8 per 100 000) where neonatal circumcision is low and socioeconomic conditions predispose patients to multiple risk factors. Western countries have a significantly lower incidence and can be as low as 0.3 per 100 000. Many risk factors have been identified including lack of circumcision, phimosis, balanitis, obesity, lichen sclerosus, smoking, and psoralen UV-A phototherapy. In addition, human papilloma virus (HPV) has been linked to nearly 40% of cases and molecular mediators continue to be investigated. SUMMARY: Although Penile cancer can be a debilitating disease, several of the known risk factors are modifiable. Public health campaigns aimed to increase awareness, promote better hygiene, and deploy HPV vaccines have had varied success at decreasing disease burden. Focus should be placed on implementing such interventions in developing countries and at-risk populations.

Management of patients with metastatic teratoma with malignant somatic transformation.

PURPOSE OF REVIEW: The purpose of this review is to examine the historical context alongside contemporary studies in order to provide the most current recommendations for the management of patients with metastatic teratoma with malignant somatic transformation (MST). RECENT FINDINGS: The main themes in the recent literature covered herein include prognostic features, the management of early-stage disease, recommended chemotherapeutic and surgical strategies as well as recognized patterns of late relapse. SUMMARY: Recent literature, combined with a significant contribution from historical studies, suggests that while MST is uncommon, its aggressive nature coupled with its resistance with traditional germ cell tumor chemotherapies makes it very difficult to manage. The key message is that surgery is recommended in all resectable MST from primary retroperitoneal lymph node dissection for clinical stage I, to radical removal of disease after chemotherapy and when chemotherapy fails. In advanced cases with documented spread of the transformed histologic subtype, systemic therapies targeted to the identified tumor type should be considered.

Predictive Nomogram for Recurrence following Surgery for Nonmetastatic Renal Cell Cancer with Tumor Thrombus.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Evidence of a dual histogenetic pathway of sacrococcygeal teratomas.

AIMS: Sacrococcygeal teratomas are rare tumours that occur most frequently in neonates, although adult cases also occur. The molecular pathogenesis of these tumours and their long-term prognosis is uncertain. We investigated the i(12p) status of a large number of primary sacrococcygeal teratomas in both children and adults, including cases with malignant germ cell tumour elements. METHODS AND RESULTS: Fifty-four sacrococcygeal teratoma specimens from 52 patients were identified, and available follow-up information was obtained. Fluorescence in-situ hybridization analysis was performed to identify isochromosome 12p [i(12p)] abnormalities on paraffin blocks of the tumours. Among the 48 paediatric patients, there were 44 teratomas and four tumours with combined teratoma and yolk sac tumour (one of whom also had primitive neuroectodermal tumour). The teratomas included 37 mature teratomas and 11 immature teratomas (four grade 1, two grade 2, and five grade 3). The 44 teratomas lacking a yolk sac tumour component were all negative for i(12p). The four tumours with a yolk sac tumour component were all positive for i(12p). The four adult cases all lacked non-teratomatous germ cell tumour components, immature elements, and i(12p). Follow-up information was available for 32 patients. Two patients with teratoma had recurrence, but were alive with no evidence of disease after long-term follow-up. One patient with combined teratoma and yolk sac tumour had recurrence 7 months after resection. The other patients were alive with no evidence of disease at last follow-up. CONCLUSIONS: Our data suggest that paediatric sacrococcygeal teratomas should be considered as two distinct groups with divergent histogenetic pathways. The prognosis of these tumours is excellent, despite rare recurrence.

Modified retroperitoneal lymph node dissection for post-chemotherapy residual tumour: a long-term update.

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.

Ambient ionization mass spectrometric analysis of human surgical specimens to distinguish renal cell carcinoma from healthy renal tissue.

Touch spray-mass spectrometry (TS-MS) is an ambient ionization technique (ionization of unprocessed samples in the open air) that may find intraoperative applications in quickly identifying the disease state of cancerous tissues and in defining surgical margins. In this study, TS-MS was performed on fresh kidney tissue (∼1-5 cm(3)), within 1 h of resection, from 21 human subjects afflicted by renal cell carcinoma (RCC). The preliminary diagnostic value of TS-MS data taken from freshly resected tissue was evaluated. Principal component analysis (PCA) of the negative ion mode (m/z 700-1000) data provided the separation between RCC (16 samples) and healthy renal tissue (13 samples). Linear discriminant analysis (LDA) on the PCA-compressed data estimated sensitivity (true positive rate) and specificity (true negative rate) of 98 and 95 %, respectively, based on histopathological evaluation. The results indicate that TS-MS might provide rapid diagnostic information in spite of the complexity of unprocessed kidney tissue and the presence of interferences such as urine and blood. Desorption electrospray ionization-MS imaging (DESI-MSI) in the negative ionization mode was performed on the tissue specimens after TS-MS analysis as a reference method. The DESI imaging experiments provided phospholipid profiles (m/z 700-1000) that also separated RCC and healthy tissue in the PCA space, with PCA-LDA sensitivity and specificity of 100 and 89 %, respectively. The TS and DESI loading plots indicated that different ions contributed most to the separation of RCC from healthy renal tissue (m/z 794 [PC 34:1 + Cl](-) and 844 [PC 38:4 + Cl](-) for TS vs. m/z 788 [PS 36:1 - H](-) and 810 [PS 38:4 - H](-) for DESI), while m/z 885 ([PI 38:4 - H](-)) was important in both TS and DESI. The prospect, remaining hurdles, and future work required for translating TS-MS into a method of intraoperative tissue diagnosis are discussed. Graphical abstract Touch spray-mass spectrometry used for lipid profiling of fresh human renal cell carcinoma. Left) Photograph of the touch spray probe pointed at the MS inlet. Right) Average mass spectra of healthy renal tissue (blue) and RCC (red).

Neoadjuvant chemotherapy in urothelial bladder cancer: impact of regimen and variant histology.

AIM: We compared the efficacy of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) versus gemcitabine/cisplatin in urothelial cancer and neoadjuvant chemotherapy (NACT) efficacy in variant histology (VH). MATERIALS & METHODS: Radical cystectomy patients were retrospectively compared with those who received NACT. Factors associated with survival, pathologic complete response (pCR) and downstaging (pDS) were evaluated in multivariable models. RESULTS: 9% of radical cystectomy patients (84/919) received NACT, with improved survival, pCR and pDS on both regimens. MVAC lead to higher pDS without an increase in pCR. On multivariable analysis, there was a nonsignificant increase in pDS with MVAC. NACT conferred similar responses in squamous and glandular differentiation VH. CONCLUSION: NACT was associated with improved survival, pCR and pDS. Furthermore, responses to NACT were not dependent on presence of VH.

The impact of bleomycin on retroperitoneal histology at post-chemotherapy retroperitoneal lymph node dissection of good risk germ cell tumors.

PURPOSE: Induction chemotherapy for International Germ Cell Cancer Collaborative Group (IGCCCG) good risk metastatic testicular cancer includes 3 cycles of bleomycin, etoposide and cisplatin (BEP x3) or 4 cycles of etoposide and cisplatin (EP x4). We examine differences in active cancer in the retroperitoneum between patients receiving BEP x3 compared to EP x4. MATERIALS AND METHODS: The Indiana University Testis Cancer database was queried to identify IGCCCG good risk patients who received BEP x3 or EP x4 induction chemotherapy before retroperitoneal lymph node dissection. The primary outcome of interest was retroperitoneal histology. The association between the use of bleomycin in the induction regimen with active cancer in the retroperitoneal specimen was tested using a propensity score adjusted analysis. RESULTS: A total of 179 men (79%) received BEP x3 while 47 (21%) received EP x4. Median age of the bleomycin, etoposide and cisplatin group was 27 years (range 15 to 50) vs 30 years (range 18 to 71) in the etoposide and cisplatin group. The incidence of active cancer in the retroperitoneal specimen at post-chemotherapy retroperitoneal lymph node dissection was significantly higher in the EP x4 group compared to the BEP x3 group (31.9% vs 7.8%, p <0.01). This significant difference in the bleomycin, etoposide and cisplatin vs etoposide and cisplatin groups remained in the propensity adjusted analysis (22.9% vs 7.8%, p=0.015). CONCLUSIONS: There was a higher incidence of active cancer in the retroperitoneal specimen in good risk patients who received 4 cycles of induction etoposide and cisplatin chemotherapy compared to 3 cycles of bleomycin, etoposide and cisplatin in this retrospective analysis. The overall burden of treatment may be higher for men receiving EP x4 for induction chemotherapy.

The changing reality of urothelial bladder cancer: should non-squamous variant histology be managed as a distinct clinical entity?

OBJECTIVES: To assess the effect of non-squamous differentiation (non-SQD) variant histology on survival in muscle-invasive bladder urothelial cancer (UC). PATIENTS AND METHODS: A cohort of 411 radical cystectomy (RC) cases performed with curative intent for muscle-invasive primary UC was identified between 2008 and June 2013. Survival analysis was evaluated using Kaplan-Meier methodology comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD variants). Multivariable cox proportional hazards regression assessed all-cause and disease-specific mortality. RESULTS: Of the 411 RC cases, 77 (19%) had non-SQD variant histology. The median overall survival (OS) for non-SQD variant histology was 28 months, whereas the NV+SQD group had not reached the median OS at 74 months (log-rank test P < 0.001). After adjusting for sex, age, pathological stage, and any systemic chemotherapy, patients with non-SQD variant histology at RC had a 1.57-times increased adjusted risk of all-cause mortality (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P = 0.030) compared with NV+SQD patients. CONCLUSIONS: While SQD behaves similarly to NV, non-SQD variant histology portends worse OS and disease-specific survival regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non-SQD variants of UC could perhaps be considered a distinct clinical entity in UC with goals for developing new treatment algorithms through novel clinical trials.

Three-tiered nodal classification system for bladder cancer: a new proposal.

AIM: To evaluate a three-tiered prognostic stratification using one, two to five and >five positive lymph nodes (LNs) and this nodal staging system performs across different pelvic LN dissection (PLND) templates and adjuvant chemotherapy status. METHODS: We evaluated 244 patients with positive LN urothelial cancer who underwent radical cystectomy and PLND between 2000 and 2011. Survival analyses utilizing the Kaplan-Meier method and log rank test were performed. Median follow-up was 55.3 months (range: 0.4-141). Multivariable Cox proportional hazards models were built to evaluate the prognostic stratification. RESULTS: Extended PLND template was performed on 152 (62.3%) patients and standard on 92 (37.7%). The median number of LNs resected was 14 in the standard group vs 22 in the extended group (p < 0.01) and positive LNs was 2 vs 3 (p = 0.09), respectively. Stratification in patients with: one positive LN, two to five positive LNs or >five positive LNs lead to 5-year recurrence-free survival of: 48.6, 34.5 and 15.9% for each group, while the 5-year overall survival was: 43.0, 22.1 and 11.3%, respectively. Stratification in the three groups was also verified irrespective of PLND template and adjuvant chemotherapy. Two multivariable models confirmed the findings when controlling for demographic features and known pathologic risk factors. CONCLUSION: Three-tiered nodal classification system using the number of metastatic LNs (one, two to five and >five) stratifies patients with lymphatic disease into distinct prognostic groups.