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.

Human papillomavirus (HPV)-induced neoplasia in the urinary bladder: a missing link?

The discovery that the role human papillomavirus (HPV) plays in the induction of human cancer represents an important achievement in oncologic research. It has taken on even greater importance since the development of vaccines, which promise the hope of preventing these cancers from ever occurring. Because of these important implications, many have attempted to determine a possible role for the virus in cancers of the urinary bladder-an organ in close anatomic proximity to the primary sites of HPV-induced neoplasia and one which already has an established oncogenic infectious agent in Schistosoma haematobium. Here we review the current literature exploring this possible role in the most common subtype of cancer of the urinary bladder, urothelial carcinoma, and two much more rare histologic subtypes that have well established roles for HPV-induced neoplasia in other anatomic sites-squamous cell carcinoma and adenocarcinoma.

Outcomes of postchemotherapy retroperitoneal lymph node dissection following high-dose chemotherapy with stem cell transplantation.

BACKGROUND: Characterizing the role of postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) after high-dose chemotherapy (HDCT) has been limited by small sample sizes. This study reports on survival after HDCT with stem cell support and PC-RPLND as well as histologic findings in the retroperitoneum. METHODS: The prospectively maintained testicular cancer database of Indiana University was queried for patients receiving HDCT with stem cell transplantation before PC-RPLND. The cause and date of death were obtained through patient chart review and contact with referring physicians. The Kaplan-Meier method was used to evaluate overall survival (OS). The log-rank test was used for tests of significance. A multivariate, backward, stepwise Cox regression model was built to evaluate predictors of overall mortality. RESULTS: A total of 92 patients were included in the study. In the entire cohort, the retroperitoneal (RP) histology findings at the time of PC-RPLND were necrosis (26%), teratoma (34%), and cancer (38%). Sixty-six patients (72%) harbored either a teratoma or active cancer in the RP specimen at PC-RPLND. The median follow-up for the entire cohort was 80.6 months. A total of 28 patients (30%) died during follow-up. The 5-year OS rate of the entire cohort was 70%. The most significant predictor of death was PC-RPLND performed in the desperation setting with elevated markers. CONCLUSIONS: Despite these patients being heavily pretreated with multiple cycles of chemotherapy, including HDCT, approximately three-fourths were found to have a teratoma and/or active cancer in the retroperitoneum. This underscores the importance of PC-RPLND for rendering patients free of disease and providing a potential for cure.

Oncologic outcomes and prognostic impact of urothelial recurrences in patients undergoing segmental and total ureterectomy for upper tract urothelial carcinoma.

INTRODUCTION: We evaluated the impact of urothelial recurrences in a cohort of patients undergoing segmental (SU) and total ureterectomy (TU) as an alternative to nephroureterectomy (NU) for upper tract urothelial carcinoma. METHODS: Between 1999 and 2012, patients who underwent SU, TU and NU for treatment of upper tract urothelial carcinoma were evaluated. Demographic, surgical, pathologic and oncologic data were collected. Recurrence-free (RFS) and disease-specific survival (DSS) were analyzed using Kaplan-Meier and multivariable Cox methods. RESULTS: A total 141 patients were evaluated, 35 underwent SU, 10 TU and 96 NU. Patients who underwent TU were more likely to have bilateral disease (p < 0.01), solitary kidney (p < 0.01), and multifocal disease (p = 0.01). Organ-confined (p < 0.01) and low-grade disease (p < 0.01) were more common in the TU and SU groups compared with NU. At a median follow-up of 56.9 months (range: 0.2-181.1) disease relapse occurred in 88 (55.3%) patients. Localized recurrence occurred in 31.1% of SU/TU group compared to 27.1% (p = 0.62) of the NU group. Neither total nor segmental ureterectomy demonstrated significantly worse RFS (p = 0.26 and p = 0.81), CSS (p = 0.96 and p = 0.52) or overall survival (p = 0.59 and p = 0.55) compared with complete NU. Localized urothelial recurrence did not confer increased risk of cancer-specific (p = 0.73) or overall mortality (p = 0.39). The paper's most important limitations include its retrospective nature and its relatively small number of patients. CONCLUSION: No significant survival differences were demonstrated between surgical approaches for upper tract urothelial cancer. Localized urothelial recurrence after surgical treatment for upper tract urothelial cancer does not affect mortality in this population. TU with ileal-substitution may provide an alternative option for patients with extensive ureteral disease and poor renal function.

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.

Does Squamous Differentiation Portend Worse Outcomes in Urothelial Bladder Cancer?

INTRODUCTION: Interest on the impact of variant histology in bladder cancer prognosis is increasing. Although squamous differentiation is the most well characterized, only recently have less common variants gained increased recognition. We assessed whether squamous differentiation conferred a worse prognosis than nonvariant urothelial bladder cancer in a contemporary cohort of patients treated with radical cystectomy given the increased awareness of other less common variants. METHODS: We identified patients with squamous differentiation or nonvariant histology on transurethral resection of bladder tumor and/or cystectomy pathology during a 10-year period. Disease specific and overall survival were evaluated using Kaplan-Meier methodology. Cox regression was used to assess variables associated with mortality. RESULTS: Between 2003 and 2013, 934 patients underwent cystectomy for urothelial bladder cancer. Overall 617 nonvariant and 118 squamous differentiation cases were identified, and the remainder was nonsquamous differentiation variant histology. Overall 75% of patients with squamous differentiation had muscle invasive disease at diagnosis compared with 59% of those with nonvariant histology (p=0.002). Nonorgan confined disease at cystectomy was more common in patients with squamous differentiation (57% vs 44%, p=0.009). Among cases on neoadjuvant chemotherapy 20% (9 of 45) of nonvariant and 13% (1 of 8) of squamous differentiation were pT0N0 (p=0.527). Median followup was 52 months. Adjusted for demographics, pathological stage and chemotherapy, squamous differentiation was not associated with an increased risk of disease specific (HR 1.35, 95% CI 0.90-2.04, p=0.150) or all cause mortality (HR 0.90, 95% CI 0.60-1.25, p=0.515). CONCLUSIONS: In a contemporary cohort of urothelial bladder cancer with recognition and characterization of less commonly described variants, squamous differentiation is not associated with a worse disease specific and all cause mortality when compared to a pure nonvariant cohort.

Contemporary bladder cancer: variant histology may be a significant driver of disease.

OBJECTIVES: To evaluate pathologic and survival outcomes among patients with variant histology (VH) urothelial carcinoma of the bladder. METHODS: A retrospective review of an institutional database was performed to identify all patients who underwent radical cystectomy with curative intent for urothelial carcinoma between 2008 and June 2013. VH was assigned by genitourinary pathologists. Descriptive statistics comparing clinicopathologic outcomes were performed using the Pearson chi-square test and analysis of variance. Survival was evaluated using the Kaplan-Meier methodology and the Cox proportional hazards regression. RESULTS: In total, 624 patients were identified. Overall, 26% (n = 162) had VH, with the most common being squamous differentiation (n = 68), micropapillary variant (MPV, n = 28), plasmacytoid variant (PCV, n = 25), and sarcomatoid variant (n = 15); 64% of MPV and 72% of PCV had positive lymph nodes. Compared with 8% of patients with a non VH, 44% of those with VH were categorized as pT4 (P<0.001). MPV and PCV were independently associated with twice the risk of all-cause mortality compared with nonvariant, when adjusting for demographics, American Society of Anesthesiologists class, transurethral resection of bladder tumor stage, cystectomy stage, positive lymph nodes, and reception of chemotherapy (odds ratio = 2.20, 95% CI: 1.28-3.78; P = 0.004; odds ratio = 2.42, 95% CI: 1.33-4.42; P = 0.004, respectively). There was no difference in risk of mortality associated with squamous differentiation or sarcomatoid variant (P>0.05 each). CONCLUSIONS: MPV and PCV are associated with increased risk of mortality. Improved recognition of VH will enable larger cohorts of study and better prognostic understanding of the significance of specific VH involvement.

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.

Lymph node metastases in patients with urothelial carcinoma variants: influence of the specific variant on nodal histology.

OBJECTIVES: The effect that the presence of urothelial variant (UV) histologies has on the behavior of urothelial carcinoma remains poorly defined. The goal of this study is to examine the relationship between different histologic variants and the presence and histology of lymph node metastases. MATERIALS AND METHODS: Our institutional bladder cancer database was examined for all patients demonstrating UV at cystectomy performed between 2001 and 2012. Patients with primary bladder sarcoma, primary bladder adenocarcinoma, and squamous cell carcinoma were excluded. The cystectomy and nodal pathology reports were reviewed in node-positive cases with the goal of determining the relative percentages of UVs in the bladder and lymph nodes. RESULTS: Overall, 292 patients demonstrated UV at cystectomy. After excluding patients with primary adenocarcinoma, sarcoma, and squamous variants, 141 patients remained, of which 65 demonstrated node-positive disease. Of these node-positive patients, 57 had slides available for review. Node positivity was most common in the micropapillary (MP), clear cell urothelial carcinoma (CC), and plasmacytoid (PC) variants. Remaining variants demonstrated node-positive rates ranging from 11.1% to 37.5%. When nodes were positive, the variants found in the nodal metastases most commonly were MP, CC, glandular, nested, and lymphoepitheliomalike. Median lymph node density was highest in PC (33%) and CC (35%) variants, although these differences were not statistically significant. Variant histology predominated the nodal metastases regardless of predominance in bladder for the MP (84%) and CC (100%) variants. The PC variant exhibited the high incidence of positive surgical margins. CONCLUSION: Lymph node metastases were most common in the MP, CC, and PC variants. Variant histology was present and predominated nodal histology in most MP and CC cases. These results suggest that the variant histology itself may be driving lymphatic spread in MP and CC cases. Conversely, the PC variant may be a marker for locally advanced and aggressive disease rather than specifically influencing lymphatic spread.

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.

Surgical management of late relapse on surveillance in patients presenting with clinical stage I testicular cancer.

OBJECTIVE: To determine survival outcomes in clinical stage I germ cell tumor (GCT) patients requiring retroperitoneal lymph node dissection (RPLND) for late relapse (LR) occurring while on surveillance. METHODS: The Indiana University Testis Cancer Database was queried from 1985 to 2013 to identify all patients who presented with clinical stage I GCT, elected surveillance, relapsed ≥ 2 years after initial diagnosis, and underwent RPLND in treatment of their LR. Clinical, pathologic, and treatment characteristics were reviewed. RESULTS: Twenty-eight patients met inclusion criteria. The mean age at diagnosis was 29.3 years. Testicular primary was pure seminoma in 2, intratubular germ cell neoplasia with scar in 1, nonseminomatous GCT in 24, and unknown in 1 patient. The median time from diagnosis to relapse was 48.5 months (range, 28-321 months). At relapse, serum tumor markers were elevated in 13 patients (46.4%). Nineteen patients were given cisplatin-based chemotherapy at LR. RPLND was initial management of LR in 9. At RPLND, 10, 5, and 13 patients demonstrated fibrosis, teratoma, and viable malignancy, respectively. On the last follow-up, 24 patients (85.7%) were free of disease and 4 patients (14.3%) had died of their disease. CONCLUSION: When examining outcomes among patients undergoing RPLND at LR of GCT, it appears that patients experiencing LR on surveillance have more favorable histology and survival outcomes than previously reported for unselected patients experiencing LR.

Critical analysis of the 2010 TNM classification in patients with lymph node-positive bladder cancer: influence of lymph node disease burden.

OBJECTIVES: In 2010, a new TNM staging system was published by American Joint Committee on Cancer, changing the nodal classification to include the presence of common iliac lymph node (LN) involvement as N3 category. The objective of this study was to define the capability of the current TNM nodal classification to separate patients with different prognostic stages and to evaluate the effect of LN disease burden. METHODS AND MATERIALS: A total of 93 patients with metastatic LNs after radical cystectomy and extended LN dissection for urothelial carcinoma of the bladder between 1999 and 2012 were included. The median follow-up was 21.5 months. The correlation between N3 and indicators of LN disease burden was analyzed using the Spearman correlation coefficient. Recurrence-free survival (RFS) and overall survival (OS) analysis was performed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: The presence of N3 disease was associated with higher number of metastatic LNs (7 vs. 2, P<0.01); however, this was highly variable and correlation coefficients between common iliac metastatic LNs and other lymphatic disease burden indicators demonstrated weak association (0.39-0.63). Patients with N1 lesions were found to have a distinct RFS and OS (P<0.01 and P = 0.01, respectively). A trend toward worse RFS (P = 0.07) and OS (P = 0.08) was observed in patients with N3 lesions. However, no difference in RFS or OS was found between patients with N2 and N3 lesions (P = 0.83 and 0.50, respectively). CONCLUSIONS: The N3 category in the current TNM classification defines a group of patients with high but heterogeneous disease burden. This may be the explanation for its lack of prognostic stratification when compared with N2 category bladder cancer.

Plasmacytoid variant urothelial bladder cancer: is it time to update the treatment paradigm?

OBJECTIVES: Plasmacytoid variant (PCV) urothelial cancer (UC) of the bladder is rare, with poor clinical outcomes. We sought to identify factors that may better inform expectations of tumor behavior and improve management options in patients with PCV UC. MATERIALS AND METHODS: A retrospective analysis of the Indiana University Bladder Cancer Database between January 2008 and June 2013 was performed comparing 30 patients with PCV UC at cystectomy to 278 patients with nonvariant (NV) UC at cystectomy who underwent surgery for muscle-invasive disease. Multivariable logistic regression was used to assess precystectomy variables associated with non-organ-confined disease at cystectomy and Cox regression analysis to assess variables associated with mortality. RESULTS: Patients with PCV UC who were diagnosed with a higher stage at cystectomy (73% pT3-4 vs. 40%, P = 0.001) were more likely to have lymph node involvement (70% vs. 25%, P<0.001), and positive surgical margins were found in 40% of patients with PCV UC vs. 10% of patients with NV UC (P<0.001). Median overall survival and disease-specific survival were 19 and 22 months for PCV, respectively. Median overall survival and disease-specific survival had not been reached for NV at 68 months (P<0.001). Presence of PCV UC on transurethral resection of bladder tumor was associated with non-organ-confined disease (odds ratio = 4.02; 95% CI: 1.06-15.22; P = 0.040), and PCV at cystectomy was associated with increased adjusted risk of mortality (hazard ratio = 2.1; 95% CI: 1.2-3.8; P = 0.016). CONCLUSIONS: PCV is an aggressive UC variant, predicting non-organ-confined disease and poor survival. Differentiating between non-muscle- and muscle-invasive disease in patients with PCV UC seems less important than the aggressive nature of this disease. Instead, any evidence of PCV on transurethral resection of bladder tumor may warrant aggressive therapy.

Short-term morbidity and mortality of Indiana pouch, ileal conduit, and neobladder urinary diversion following radical cystectomy.

PURPOSE: Literature surrounding Indiana pouch (IP) urinary diversion suggests a higher incidence of complications and longer operative time compared with ileal conduit (IC) and neobladder (NB). We sought to assess short-term complications of IP diversions compared with other diversions at our institution. MATERIALS AND METHODS: Using institutional National Surgical Quality Improvement Program data, we identified radical cystectomy cases performed for bladder cancer at Indiana University from January 2011 until June 2013. During this time period, the National Surgical Quality Improvement Program randomly evaluated approximately 70% of radical cystectomies performed for urothelial carcinoma at our institution. Multivariable logistic regression was performed to identify factors associated with Clavien grade III-V complications. RESULTS: A total of 233 cases were identified, 139 IC, 39 IP, and 55 NB. Mean (standard deviation) operative times for IC, IP, and NB were 257 (84), 383 (78), and 327 (88) minutes, respectively (P<0.001). Half of the patients required blood transfusion during the hospitalization. The overall rate of complications was significantly lower among NB (P = 0.009). Overall, 12% of patients developed a Clavien grade III-V complication, with no difference observed between groups (P = 0.884). After controlling for preoperative confounders, IP patients were not at increased odds of developing a Clavien III-V complication compared with IC (odds ratio = 1.38, P = 0.599). CONCLUSIONS: At a high-volume center, the incidence of serious complications was similar between diversion types. IP patients were more likely to experience minor complications. Patients should be counseled regarding rates of short-term complications and blood transfusion.

The expression patterns of p53 and p16 and an analysis of a possible role of HPV in primary adenocarcinoma of the urinary bladder.

BACKGROUND: Primary adenocarcinoma of the urinary bladder is rare. The molecular and cellular events leading to its pathogenesis are not well delineated. The goal of this study was to investigate p53 and p16 expression, as well as HPV status, in a relatively large series of primary bladder adenocarcinomas. MATERIALS AND METHODS: Thirty six cases of urinary bladder adenocarcinoma were chosen from participating institutions. The diagnosis and available clinical history were reviewed in each case. Immunostains for p53, p16 and HPV and high-risk and low-risk HPV-ISH were performed on all tumors. RESULTS: Patients had an average age of 61 years with a male predominance (1.5 ∶ 1 male ∶ female ratio). The average tumor size in cystectomy specimens was 4.3 cm. Of the cases managed by transurethral resection, 40% were pT2 at the time of diagnosis. In cystectomy specimens, 77% were either pT3 or pT4. Strong nuclear p16 expression was seen in 67% of all cases and p53 expression was present in 58% of the cases. Expression of both markers was seen in 33% of cases. Expression of p16 or p53 alone was present in 12 (33%) and 9 (25%) cases, respectively. Neither marker was expressed in only 3 (8%) of the tumors. No significant correlation between clinical variables and any of the markers we studied was identified. No HPV infection was detected in any case. CONCLUSIONS: Expression of p53 and/or p16 is very common in urinary bladder adenocarcinoma. These findings implicate a high likelihood that alterations in these cell cycle proteins contribute to the pathogenesis of these tumors. Despite frequent immunohistochemical labeling for p16, no evidence of HPV infection was found.

Plasmacytoid bladder cancer: variant histology with aggressive behavior and a new mode of invasion along fascial planes.

OBJECTIVE: To examine differences in disease progression and nature of tumor invasion that may lead to more accurate expectations of tumor behavior and improved management options for plasmacytoid variant (PCV) histology urothelial bladder cancer patients. METHODS: Using the Indiana University Bladder Cancer Database, we conducted a retrospective analysis of patients undergoing radical cystectomy from 2008 to June 2013 to identify patients with PCV, micropapillary variant (MPV), or nonvariant (NV) histology and either positive ureteral margins (+UM), paravesical surgical margins (+PSM), or lymph node (+LN) involvement. Pearson's chi-squared test and analysis of variance were used for descriptive analysis. RESULTS: Of 510 patients who met inclusion criteria, 30 had +UM on final pathology. The incidence of +UM in NV patients was 17 of 457 (3.7%), in MPV 5 of 28 (17.9%), and in PCV 8 of 25 (32.0%) (P <.001). Carcinoma in situ on the luminal margin was noted for all cases, except in 5 of the 8 PCV patients with +UM, in whom retrograde longitudinal invasion along the subserosal and adventitia was noted. +PSM and +LN were significantly higher for both PCV (28.0%, 72.0%) and MPV (10.7%, 64.3%) than NV (2.6%, 18.6%, P <.001, each). CONCLUSION: PCV exhibits a unique pattern of spread along the ureter. This proposes a new mode of invasion along the fascial sheath. The incidence of +PSM and +LN liken PCV to the known aggressive MPV, and in conjunction with the increased incidence of +UM, may lead to a paradigm shift, with surgeons and pathologists being more vigilant with surgical margins.

Reoperative retroperitoneal lymph node dissection for metastatic germ cell tumors: analysis of local recurrence and predictors of survival.

PURPOSE: While reoperative retroperitoneal lymph node dissection results in durable long-term survival, outcomes are comparatively worse than in patients who undergo initial adequate resection. We identified predictors of cancer specific survival and correlated technical aspects of initial resection to local recurrence in patients treated with repeat retroperitoneal lymph node dissection. MATERIALS AND METHODS: We reviewed subsequent data on 203 patients treated with reoperation for recurrent retroperitoneal germ cell tumor after initial retroperitoneal lymph node dissection with local relapse. We used multivariate Cox proportion hazard models for cancer specific survival and multivariate logistic regression for local recurrence. RESULTS: The only 2 factors associated with local recurrence at lymph node dissection were incomplete lumbar vessel division at initial resection (p<0.01) and teratoma histology in the reoperative pathology specimen (p=0.01). Median followup was 73 months. Initial survival analysis including preoperative variables indicated that active cancer at initial operation (p=0.04), increased serum tumor markers (p=0.02), M1b stage (p<0.01) and salvage chemotherapy (p=0.01) were independent predictors of worse cancer specific survival. After introducing the final pathological data from reoperation into the final multivariate model only active cancer at reoperation (p<0.01), M1b stage (p=0.01) and salvage chemotherapy before reoperation (p=0.02) retained the association with worse oncologic outcomes. CONCLUSIONS: Tumor biology and inadequate surgical technique (incomplete lumbar ligation) are associated with local recurrence after initial retroperitoneal lymph node dissection. Decreased cancer specific survival is expected in this population, mostly driven by active cancer in the final pathology specimen.

Lymph node-positive bladder cancer: surgical, pathologic, molecular and prognostic aspects.

The presence of lymphatic metastasis is associated with markedly worse prognosis in patients with bladder cancer, although surgical resection and chemotherapy can still provide long-term survival for selected patients. The prognostic stratification of patients with positive lymph nodes has been broadly discussed in the current literature and a more extensive pelvic lymph node dissection and thorough pathologic assessment has been advocated. It is clear that stratification using the tumor node metastasis staging system is insufficient to adequately discriminate prognosis between patients with different lymph node involvement. Lymph node density and extranodal extension have been extensively investigated and appear to influence the prognosis of these patients. Molecular markers have been developed to improve the diagnosis of micrometastatic disease, and new targeted therapies have shown promising preclinical results and are now being tested in different clinical scenarios.