The increase of stage, grading, and metastases in patients undergoing radical prostatectomy during the last decade.

PURPOSE: To investigate changes in clinical data and pathological features of prostatectomy specimens of prostate cancer (PCa) patients in a large tertiary care center over the last 12 years as potential consequence of reduced acceptance of prostate-specific antigen (PSA)-based screening and implementation of active surveillance as a therapeutic option in PCa. METHODS: We retrospectively identified all patients with PCa who underwent radical prostatectomy at our institution between 2004 and 2016 from our clinical database. We reviewed clinical and pathological data including patient age, PSA level, number of positive cores and Gleason score in prostate biopsy, and pathologic N- and T-stage, and Gleason score in radical prostatectomy specimen. RESULTS: Data of 5497 consecutive patients were analyzed. Median PSA increased from 7 (IQR 4.8-10.5) to 9 ng/ml (IQR 5.8-16.1; p < 0.001), and median number of positive biopsy cores increased from 3 (IQR 2-5) to 5 (IQR 3-7; p < 0.001). The proportion of patients with Gleason score ≥ 7 in biopsy and prostatectomy specimens increased from 40 to 78% and 49 to 89% (p < 0.001), respectively. The rate of locally advanced (≥ pT3a) and lymph node-positive tumors increased from 28 to 43% and 5 to 16% (p < 0.001), respectively. CONCLUSIONS: We observed a significant change in clinical and pathological findings in our prostatectomy series with a significantly higher proportion of aggressive and locally advanced PCa in recent years. These findings may be related to a reduced acceptance of PSA-based screening and the use of active surveillance as management strategy and have significant impact on daily patient care.

Comparison of prostate positioning guided by three-dimensional transperineal ultrasound and cone beam CT.

OBJECTIVE: The accuracy of a transperineal three-dimensional ultrasound system (3DUS) was assessed for prostate positioning and compared to fiducial- and bone-based positioning in kV cone beam computed tomography (CBCT) during definitive radiotherapy of prostate cancer. METHODS: Each of the 7 patients had three fiducial markers implanted into the prostate before treatment. Prostate positioning was simultaneously measured by 3DUS and CBCT before each fraction. In total, 177 pairs of 3DUS and CBCT scans were collected. Bone-match and seed-match were performed for each CBCT. Using seed-match as a reference, the accuracy of 3DUS and bone-match was evaluated. Systematic and random errors as well as optimal setup margins were calculated for 3DUS and bone-match. RESULTS: The discrepancy between 3DUS and seed-match in CBCT (average ± standard deviation) was 0.0 ± 1.7 mm laterally, 0.2 ± 2.0 mm longitudinally, and 0.3 ± 1.7 mm vertically. Using seed-match as a reference, systematic errors for 3DUS were 1.2 mm, 1.1 mm, and 0.9 mm; and random errors were 1.4 mm, 1.8 mm, and 1.6 mm, on lateral, longitudinal, and vertical axes, respectively. By analogy, the difference of bone-match to seed-match was 0.1 ± 1.1 mm laterally, 1.3 ± 3.8 mm longitudinally, and 1.3 ± 4.5 mm vertically. Systematic errors were 0.5 mm, 2.2 mm, and 2.6 mm; and random errors were 1.0 mm, 3.1 mm, and 3.9 mm on lateral, longitudinal, and vertical axes, respectively. The accuracy of 3DUS was significantly higher than that of bone-match on longitudinal and vertical axes, but not on the lateral axis. CONCLUSION: Image-guided radiotherapy of prostate cancer based on transperineal 3DUS was feasible, with overall small discrepancy to seed-match in CBCT in this retrospective study. Compared to bone-match, transperineal 3DUS achieved higher accuracy on longitudinal and vertical axes.

Postoperative upgrading of prostate cancer in men ≥75 years: a propensity score-matched analysis.

PURPOSE: Gleason score upgrading should be considered when indicating surgery in prostate cancer (PCa) patients. In elderly patients, definitive treatment of low-risk PCa must be weighed with the risks of overtreatment. Our aim was to evaluate rates of Gleason score upgrading in patients ≥75 years undergoing radical prostatectomy (RP) for localized PCa and to identify predictors associated with upgrading. METHODS: 3296 patients undergoing RP were retrospectively evaluated and categorized into age groups: <70 years (n = 2971) vs. ≥75 years (n = 325). We analyzed prostate-specific antigen (PSA), biopsy counts, Gleason score, pathologic T- and N-stage, and surgical margin. Propensity score matching was performed to compare rates of up- and downgrading on surgical specimen using the new five-tier pathologic grading system. Logistic regression was used to identify independent predictors of upgrading. RESULTS: Preoperatively, patients ≥75 years had higher PSA (8.8 vs. 7.3 ng/mL) and lower proportion of grade group 1 (Gleason score 6) at biopsy (29.2 vs. 47.9%; both p < 0.001) compared to patients <70 years. At RP, patients ≥75 years were more likely to have extraprostatic disease (50 vs. 30%) and lower rates of grade group 1 (14.1 vs. 34.8%; both p < 0.001). Postoperative downgrading was similar (15.1 vs. 19.5%). However, patients ≥75 years had higher rates of postoperative upgrading (46.6 vs. 27.9%; p < 0.001). Age ≥75 years, higher PSA levels at RP, and an increased number of positive biopsy cores were associated with upgrading. CONCLUSIONS: Patients ≥75 years not only demonstrated higher rates of advanced disease but more frequent upgrading on RP specimen. Age ≥75 years, higher PSA levels at RP, and an increased number of positive biopsy cores were predictive for upgrading. The increased risk of upgrading should be taken into consideration when discussing optimal treatment for this specific cohort.

Dosimetry for (177)Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer.

PURPOSE: Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand (177)Lu-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer. METHODS: Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) (177)Lu-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines. RESULTS: The average (± SD) absorbed doses per cycle were 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 ± 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 ± 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle. CONCLUSION: The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with (177)Lu-DKFZ-PSMA-617. We suggest that (177)Lu-DKFZ-PSMA-617 is suitable for radiotherapy, offering tumour-to-kidney ratios comparable to those with RLT agents currently available for the treatment of neuroendocrine tumours. Our dosimetry results suggest that (177)Lu-DKFZ-PSMA-617 treatment with higher activities and more cycles is possible without the risk of damaging the kidneys.

Prognostic value of prior history of urothelial carcinoma of the bladder in patients with upper urinary tract urothelial carcinoma: results from a retrospective multicenter study.

BACKGROUND: Patients with urothelial carcinoma (UC) often develop multifocal metachronous tumors throughout the genitourinary tract. In the present study, we evaluated the prognostic value of prior history of UC of the bladder (UCB) in patients with upper tract urothelial carcinoma (UTUC) in an international multi-institutional cohort. PATIENTS AND METHODS: Data from 785 patients who underwent radical nephroureterectomy (RNU) with ipsilateral bladder cuff resection at nine academic institutions in Europe and the USA between 1987 and 2008 were reviewed. Log-rank tests and Cox proportional hazards regression models were used for univariable and multivariable analyses. RESULTS: The median follow-up of the whole cohort was 34 months (interquartile range 15-66 months). Five hundred and fifty-eight (72 %) patients had no UCB before the diagnosis of UTUC; a prior history of non-muscle-invasive and muscle-invasive UCB before the UTUC was found in 179 (23 %) and 36 (5 %), respectively. History of UCB before RNU was an independent predictor of both recurrence-free survival (p = 0.012; no UCB vs. non-muscle-invasive UCB: hazard ratio (HR) 1.4, p = 0.082; no UCB vs. muscle-invasive UCB: HR 2.1, p = 0.007) and cancer-specific survival (p = 0.008; no UCB vs. non-muscle-invasive UCB: HR 1.2, p = 0.279; no UCB vs. muscle-invasive UCB: HR 2.3, p = 0.008) on multivariable Cox regression analyses that included age, gender, surgical type, stage, grade, presence of concomitant carcinoma in situ, presence of lymphovascular invasion, and lymph node status. CONCLUSIONS: Prior history of muscle-invasive UCB was significantly associated with an increased risk of disease recurrence and cancer-specific death in patients with UTUC.

Real-time magnetic resonance imaging (MRI): anatomical changes during physiological voiding in men.

OBJECTIVE: To investigate the interactions between the bladder, urethra, pelvic floor and the function of the prostate during 'normal' voiding. PATIENTS AND METHODS: In all, 16 men with no history of urinary incontinence, urgency or obstructive voiding dysfunction were enrolled. We analysed the interaction between the bladder, urethra, pelvic floor and changes in the prostate during the Valsalva manoeuvre and voiding using real-time magnetic resonance imaging (rtMRI). The axis through the external sphincter (AES) to pubo-coccygeal line (PC-line) and the angle between the axis of the os pubis (AOP) and ventral prostate (VP) was measured before and at the end of voiding. Additionally, the angle between the AOP and the VP was measured during the Valsalva manoeuvre. Change of position, or contraction, of the VP was measured. RESULTS: The mean age of the men was 69.8 years and mean prostate volume 33.1 mL. Before voiding, the mean AES to PC-line was 10.5 mm. At the end of voiding, the mean AES to PC-line was 20 mm. The mean angle between AOP/VP was 31.6° in the storage phase and increased to a mean of 54.5° during voiding. During the Valsalva manoeuvre, the angle between the AOP/VP remained constant. There was a mean vertical contraction of the VP of 48.25 mm before voiding and a declining of the cranio-caudal distance of the VP with a mean of 33.92 mm during voiding. CONCLUSIONS: All the men in our study showed relaxation of the pelvic floor, followed by a descent of the bladder neck. Voiding could not be initiated unless the prostate rotated around the symphysis. The study suggests that both the rotation and a vertical contraction of the prostate precede voiding. The anatomy of physiological voiding or voiding dysfunction can be investigated non-invasively using rtMRI.

Prognostic role of ECOG performance status in patients with urothelial carcinoma of the upper urinary tract: an international study.

OBJECTIVE: To evaluate the prognostic role of ECOG Performance status (ECOG-PS) in a large multi-institutional international cohort of patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. MATERIALS AND METHODS: Data of 427 patients treated with radical nephroureterectomy at five international institutions in Asia, Europe and Northern America were collected retrospectively from 1987 to 2008. Logistic and Cox regression models were used for univariable and multivariable analyses. RESULTS: ECOG-PS was 0 in 272 of 427 (64%) patients. The median follow-up of the whole cohort was 32 months. The five-year recurrence-free (RFS), cancer-specific (CSS) and overall (OS) survival estimates were 71.7%, 74.9% and 68.5%, respectively, in patients with ECOG-PS 0 compared with 60.1%, 67.8%, and 51.4% respectively, in patients with ECOG-PS ≥1 (P value 0.08 for RFS, 0.43 for CSS, and <0.001 for OS, respectively). On multivariable Cox regression analyses, ECOG-PS was not an independent predictor of either RFS (hazard ratio 1.4; P = 0.107) or CSS (hazard ratio 1.2; P = 0.426) but was an independent predictor of OS (hazard ratio 1.5; P = 0.03). CONCLUSIONS: In this large multicentre international study, ECOG-PS was not significantly associated with RFS and CSS. Conversely we find a strong association with survival 1-month after surgery and OS. Further research is needed to ascertain the additive prognostic role of ECOG-PS in well-designed prospective multicentre studies.

Staging of muscle-invasive bladder cancer: can computerized tomography help us to decide on local treatment?

OBJECTIVES: To assess the power of multi-detector row computerized tomography (MDCT) in daily routine as a basic staging procedure for the decision on local treatment of patients with bladder cancer. PATIENTS AND METHODS: We retrospectively analysed 276 patients who had undergone radical cystectomy between 2004 and 2008 and correlated the MDCT findings with pathological findings, number of removed lymph nodes and type of urinary diversion. RESULTS: Accuracy of MDCT in predicting pathological tumour stage was 49% (kappa coefficient, 0.23; P < 0.001). Overstaging occurred in 23.4%, and understaging occurred in 24.7%. Accuracy in predicting lymph node metastases was 54% (kappa coefficient, 0.04; P = 0.297). Overstaging and understaging occurred in 8.3 and 29.4%, respectively. Significantly more ileal conduits were performed in patients with high postoperative pathological tumour stages (P = 0.04) and positive lymph nodes (P = 0.013). In contrast, there was no correlation between preoperative CT tumour/nodal stage and the number of removed lymph nodes (P = 0.44 and P = 0.732, respectively), and between preoperative tumour stage and type of urinary diversion (P = 0.126). CONCLUSIONS: MDCT as a preoperative staging procedure has a low accuracy in predicting the correct tumour and nodal stage, and therefore, it has little impact on decision-making for local treatment of muscle-invasive bladder cancer during radical cystectomy.

Single-stage dorsal inlay for reconstruction of recurrent peno-glandular stenosis.

OBJECTIVE: To evaluate the validity of a single-stage dorsal inlay for recurrent peno-glandular stenosis following previous endourological or open urethroplastic surgery. Urethral glanular reconstruction included a deep dorsal incision followed by complete scar excision to create a deep groove presenting well-vascularized recipient bed ensuring appropriate graft healing. MATERIALS AND METHODS: Between April 2002 and January 2008, a total of 34 patients (mean age 51.5 years, 14-85 years) were enrolled in the study. Congenital anomalies included hypospadia (n = 19, 53%) and epispadia (n = 2, 6%). Condition of strictures was either iatrogenic (n = 7), due to infection (n = 5), or traumatic (n = 1). Foreskin grafts were used in 13 cases, foreskin and buccal mucosa in one case, penile skin in 6 cases, and inguinal skin/thigh (harvested by electrodermatom) in 14 cases. The combination of meticulous scar excision with a deep incision of the glans was used to provide a well-vascularized grafting bed, thus ensuring excellent graft healing. The outcome analysis included urinary flow, urethral calibration >18 ch, voiding cystometry, and patient's satisfaction in a follow-up regime every 3 months. RESULTS: The average graft length was 4.7 cm (median 8, range 1.5-14). Mean follow-up was 70 months. In 31 patients (91%), no recurrent glanular stenosis was observed resulting in a post-operative flow of average 26.2 ml/s (11-53). Three post-operative wound infections occurred resulting in stricture recurrence, which was treated with internal urethrotomy, buccal mucosa, or penile skin inlay, respectively. Cosmetic results were satisfactory in all patients. Post-operative voiding parameters were significantly improved (P < 0.001). CONCLUSION: The single-stage dorsal inlay for reconstruction of peno-glandular stenosis represents a reliable method even if the urethral plate is severely scarred or has been excised during previous surgery. The good results imply that a well-vascularized graft and the technical approach seem to be more important than the substitute material.

Impact of bacillus Calmette-Guerin intravesical therapy on the diagnostic efficacy of The Paris System for Reporting Urinary Cytology in patients with high-grade bladder cancer.

BACKGROUND: In high-grade urothelial carcinoma (UC) of the bladder, bacillus Calmette-Guerin (BCG) therapy is a therapeutic mainstay, and urinary cytology is recommended to detect recurrences. However, intravesical BCG instillations can induce morphologic changes in urothelial cells. The authors investigated the impact of BCG therapy on the efficacy of urinary cytology. METHODS: Matched pathology and cytology samples from patients undergoing transurethral resection of the bladder after BCG therapy were assessed. Cytology samples were graded according to The Paris System for Reporting Urinary Cytology. Diagnostic quality criteria were tested for different cutoff definitions, and the results were compared between those obtained <100 versus ≥100 days after the last BCG instillation. In addition, the oncologic outcome of false-positive results was assessed. RESULTS: In total, 389 matched cases from 197 patients who had a history of high-grade UC (HGUC) were identified. Sixty cases (15.7%) were diagnosed as high-grade urothelial bladder cancer. The cytology diagnoses were as follows: non-HGUC, 191 cases (49.1%); atypical urothelial cells, 80 cases (20.6%); suspicious for HGUC, 56 cases (14.4%); and HGUC, 56 cases (14.4%). Interrater reliability was substantial (κ = 0.660). Sensitivity increased from 45% to 75% when cases diagnosed as suspicious for HGUC were also counted as positive. Notably, sensitivity was reduced within the first 100 days after BCG therapy (61.9%) compared with sensitivity at longer intervals (82.1%). Reactive atypia (odds ratio, 4.155; 95% confidence interval, 2.136-8.085; P < .001) and cellular degeneration (odds ratio, 5.050; 95% CI, 2.094-12.175; P < .001) of urothelial cells were associated with false-positive rates, and 44.7% of patients who had a false-positive cytology classification presented with HGUC during follow-up. CONCLUSIONS: BCG therapy has a short-term adverse impact on the efficacy of urinary cytology. After BCG therapy, cases classified as suspicious for HGUC should be considered positive. Importantly, patients with false-positive cytology findings should be closely monitored.

Volar onlay urethroplasty for reconstruction of female urethra in recurrent stricture disease.

OBJECTIVE: • To report our experience with a new and simple method of urethral repair with a volar onlay of free labium minus graft. Strictures of the female urethra are rare, and it is well accepted that the therapeutic options of dilation and urethrotomy are not lasting solutions as a result of their high recurrence rates. However, there is no consensus regarding the best way to reconstruct the female urethra in the case of stricture disease. PATIENTS AND METHODS: • Four consecutive female patients with a long lasting history of recurrent urethral strictures underwent open urethroplasty with a volar situated free split thickness epidermal graft from the labium minus. • The surgical technique is described and a short-term follow-up is presented. RESULTS: • Operating time was 40-140 min (mean 105 min), and the graft measured between 2 × 1.5 cm and 3 × 2.5 cm. Follow-up time was 11-19 months. Maximum urinary flow rate could be improved from a baseline of 9.4-11.2 mL/s (preoperatively, after intermittent use of dilation) to 19-23 mL/s. • Postvoid residual urine volume was 0-50 mL preoperatively and no postvoid residual urine volume postoperatively. • Urinary catheters were removed after 21 days. Urinary stress incontinence did not occur postoperatively. No complications related to the graft donor site were found. CONCLUSIONS: • The reported data concerning a new therapeutic approach for the treatment of recurrent female urethral stricture show that a volar onlay urethroplasty represents a feasible, safe and simple surgical method. • Larger series with long-term follow-up are needed for further evaluation.

Oncological outcomes after laparoscopic and open radical nephroureterectomy: results from an international cohort.

OBJECTIVE: • To compare oncological outcomes in patients undergoing open radical nephroureterectomy (ONU) with those in patients undergoing laparoscopic radical nephroureterectomy (LNU). PATIENTS AND METHODS: • A total of 773 patients underwent radical nephroureterectomy at nine centres worldwide; 703 patients underwent ONU and 70 underwent LNU. • Demographic, perioperative and oncological outcome data were collected retrospectively. • Statistical analysis of data was performed using chi-squared, Mann-Whitney U- and log-rank tests, and Cox regression analyses. • The median (interquartile range) follow-up for the cohort was 34 (15-65) months. RESULTS: • The two groups were well matched for tumour stage, presence of lymphovascular invasion (LVI) and concomitant carcinoma in situ (CIS). • There were more high-grade tumours (77.1% vs. 56.3%; P < 0.001) but fewer lymph node positive patients (2.9% vs. 6.8%; P= 0.041) in the LNU group. • Estimated 5-year recurrence-free survival (RFS) was 73.7% and 63.4% for the ONU and LNU groups, respectively (P= 0.124) and estimated 5-year cancer-specific survival (CSS) was 75.4% and 75.2% for the ONU and LNU groups, respectively (P= 0.897). • On multivariable analyses, which included age, gender, race, previous endoscopic treatment for bladder cancer, technique for distal ureter management, tumour location, pathological stage, grade, lymph node status, LVI and concomitant CIS, the procedure type (LNU vs. ONU) was not predictive of RFS (Hazard ratio [HR] 0.80; P= 0.534) or CSS (HR 0.96; P= 0.907). CONCLUSION: • The present study is the second large, independent, multicentre cohort to show oncological equivalence between ONU and LNU for well selected patients with upper urinary tract urothelial cancer, and the first to suggest parity for the techniques in patients with unfavourable disease.

Racial differences in the outcome of patients with urothelial carcinoma of the upper urinary tract: an international study.

OBJECTIVE: •To assess the impact of differences in ethnicity on clinico-pathological characteristics and outcomes of patients with upper urinary tract urothelial carcinoma (UTUC) in a large multi-center series of patients treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: •We retrospectively collected the data of 2163 patients treated with RNU at 20 academic centres in America, Asia, and Europe. •Univariable and multivariable Cox regression models addressed recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: •In all, 1794 (83%) patients were Caucasian and 369 (17%) were Japanese. All the main clinical and pathological features were significantly different between the two ethnicities. •The median follow-up of the whole cohort was 36 months. At last follow-up, 554 patients (26%) developed disease recurrence and 461 (21%) were dead from UTUC. •The 5-year RFS and CSS estimates were 71.5% and 74.2%, respectively, for Caucasian patients compared with 68.8% and 75.4%, respectively, for Japanese patients. •On univariable Cox regression analyses, ethnicity was not significantly associated with either RFS (P= 0.231) or CSS (P= 0.752). •On multivariable Cox regression analyses that adjusted for the effects of age, gender, surgical type, T stage, grade, tumour architecture, presence of concomitant carcinoma in situ, lymphovascular invasion, tumour necrosis, and lymph node status, ethnicity was not associated with either RFS (hazard ratio [HR] 1.1; P= 0.447) or CSS (HR 1.0; P= 0.908). CONCLUSIONS: •There were major differences in the clinico-pathological characteristics of Caucasian and Japanese patients. •However, RFS and CSS probabilities were not affected by ethnicity and race was not an independent predictor of either recurrence or cancer-related death.

No overt influence of lymphadenectomy on cancer-specific survival in organ-confined versus locally advanced upper urinary tract urothelial carcinoma undergoing radical nephroureterectomy: a retrospective international, multi-institutional study.

PURPOSE: Lymph node dissection (LND) is not routinely performed during radical nephroureterectomy (RNU) in upper tract urothelial carcinomas (UTUC), and its clinical relevance is unclear. The purpose of the present study was to evaluate the impact of LND on clinical outcomes in a large multicenter series of RNU for UTUC. METHODS: Detailed data on 785 patients subject to RNU were provided by nine international academic centers. The choice to perform lymphadenectomy was determined by the treating surgeon. All pathology slides were evaluated by dedicated genitourinary pathologists. Univariable and multivariable Cox regression models evaluated the association of nodal status with recurrence-free (RFS) and cancer-specific (CSS) survival. RESULTS: One hundred and ninety patients had LND. Pathological N stage was pN0 in 17%, pNx in 76%, and pN+ in 7%. The median follow-up period of the entire cohort was 34 months (interquartile range [IQR]: 15-65 months). Overall, five-year RFS and CSS estimates were 72.2 and 76%, respectively. In multivariable Cox regression analyses, pN0/pNx substaging was not an independent predictor of either RFS (hazard ratio [HR]: 1.1; P = 0.631) or CSS (HR: 1.3; P = 0.223). Similar results were obtained in a subgroup analysis limited to patients with organ-confined disease (HR: 0.9; P = 0.907 for RFS; HR: 0.4; P = 0.419 for CSS). Conversely, in patients with locally advanced disease, patients with pN0 disease have significantly better cancer-related outcomes (HR: 0.3; P < 0.001 for RFS; HR: 0.3; P < 0.001 for CSS). CONCLUSION: The present series suggests pNx is more significantly associated with a worse prognosis than pN0, but only in patients with locally advanced UTUC.

Gender differences in radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: Women have been associated with adverse outcomes after radical cystectomy for lower tract urothelial carcinoma. We evaluated the prognostic value of gender in an international cohort of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively studied 754 patients treated with RNU for UTUC without neoadjuvant chemotherapy at nine centers located in Asia, Canada, and Europe. Univariable and multivariable Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. Median follow-up was 40 months (interquartile range: 18-75). RESULTS: The majority of patients was of men (516, 68.4%). Women were older than men at the time of RNU (median: 69.2 vs. 66.5 years; P = 0.0003). Women were less likely to have high-grade disease, undergo lymph node dissection, and to receive adjuvant chemotherapy. Gender was not associated with pathologic stage, lymph node metastasis, lymphovascular invasion, concomitant CIS, tumor architecture, or tumor necrosis. On univariable Cox regression analyses, there was no association between gender and cancer recurrence (P = 0.76) or cancer-specific mortality (P = 0.30). On multivariable Cox regression analyses that adjusted for the effects of clinicopathologic features, gender was not associated with disease recurrence (P = 0.47) or cancer-specific survival (P = 0.15). CONCLUSIONS: We found no difference in histopathologic features and outcomes between men and women treated with RNU for UTUC. Nevertheless, epidemiologic and mechanistic molecular studies should be encouraged to design, analyze, and report gender-specific associations to aid in our understanding of gender impact on UTUC incidence, progression, and metastasis.

Concomitant carcinoma in situ as an independent prognostic parameter for recurrence and survival in upper tract urothelial carcinoma: a multicenter analysis of 772 patients.

PURPOSE: The purpose of this study is to assess the association of concomitant carcinoma in situ (CIS) with disease recurrence and cancer-related death in a multi-institutional series of patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: We collected retrospectively the data of 772 patients treated with RNU and ipsilateral bladder cuff excision at 9 international institutions in Asia, Europe, and Northern America from 1987 to 2008. Surgical specimens were processed according to standard pathologic procedures at each institution. Univariable and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality. RESULTS: Concomitant CIS was present in 88 patients (11.4%); it was associated with more advanced pathologic stage, higher tumor grade, and presence of lymphovascular invasion (all P-values < 0.05). The five-year recurrence-free (RFS) and cancer-specific survival (CSS) estimates were 74.4 and 76.3%, respectively, in the absence of CIS compared with 56.4 and 59.9%, respectively, in the presence of CIS (P-values < 0.0001 for RFS and 0.002 for CSS, respectively). On multivariable Cox regression analyses, concomitant CIS was an independent predictor of both RFS (hazard ratio (HR): 1.9; P = 0.007) and CSS (HR: 1.7, P = 0.048). Similar findings were reconfirmed in subgroups analyses limited to T2, organ confined, and N0/Nx UTUC, or patients who did not receive adjuvant chemotherapy. CONCLUSIONS: Presence of concomitant CIS is an independent predictor of both RFS and CSS in patients treated with RNU for UTUC. This information may be useful in risk stratification of UTUC patients for follow-up and additional therapy.