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.

[Management of urethral stricture]. / Management von Harnröhrenstrikturen.

Urethral strictures most frequently affect the bulbar but are also observed in the penile, glandular, or membranous urethra. They are often iatrogenic. Radiologic diagnosis can be established easily and safely by cystourethrography. Simple Sachse urethrotomy can result in permanent relief in the case of short bulbar strictures in initial findings. Recurrent structures or strictures in other locations should however be treated by open surgery, as cure cannot be achieved by other means. Depending on the diagnosis and comorbidities, end-to-end anastomosis, graft/flap urethroplasty, or perineal urethrostomy can be performed. If open surgery is delayed, aggravation of the diagnosis and worsening of the prognosis can be expected, regardless of the applied treatment.

[Quality medicine initiative in urology]. / Initiative Qualitätsmedizin in der Urologie.

To ensure that high quality, individualized treatment is systematically guaranteed, instruments and mechanisms, which are associated with an increasing number of interwoven processes and interfaces, are increasingly required in complex clinical routine. The main task of internal quality management is to optimize and standardize clinical processes and procedures in order to ensure quality of care. However, external assessment of these processes is also an important part of quality assurance. One of these external assessments can be carried out via the quality medicine initiative (Initiative Qualitätsmedizin). It provides a platform through which participating hospitals can continuously improve quality of care through three mechanisms: assessment of treatment quality using routine data, the transparency of this data, and use of an external peer review process.

Can we define reliable risk factors for anastomotic strictures following radical prostatectomy?

BACKGROUND: To identify risk factors for anastomotic strictures in patients after radical prostatectomy. METHODS: In all, 140 prostate cancer patients with one or more postoperative anastomotic strictures after radical prostatectomy were included. All patients underwent transurethral anastomotic resection at the University Hospital of Munich between January 2009 and May 2016. Clinical data and follow-up information were retrieved from patients' records. Statistical analysis was done using Kaplan-Meier curves and log rank-test with time to first transurethral anastomotic resection as endpoint, Chi-square-test, and Mann-Whitney-U test. RESULTS: In all, 140 patients with a median age of 67 years (IQR: 61-71 years) underwent radical prostatectomy. Median age at time of transurethral anastomotic resection was 68 years (IQR: 62-72). Patients needed 2 surgical interventions in median (range: 1-15). Median time from radical prostatectomy to transurethral anastomotic resection was 6 months (IQR: 3.9-17.4). Median duration of catheterization after radical prostatectomy was 10 days (IQR: 8-13). In all, 26% (36/140) received additional radiotherapy. Regarding time to first transurethral anastomotic resection, age and longer duration of catheterization after radical prostatectomy with a cutoff of 7 days showed no statistically significant differences (p = 0.392 and p = 0.141, respectively). Tumor stage was no predictor for development of anastomotic strictures (p = 0.892), and neither was prior adjuvant radiation (p = 0.162). Potential risk factors were compared between patients with up to 2 strictures (low-risk) and patients developing > 2 strictures (high-risk): high-risk patients had more often injection of cortisone during surgery (14% vs 0%, p < 0.001) and more frequently advanced tumor stage pT > 2 (54% vs 38%, p = 0.055), respectively. Other risk factors did not show any significant difference compared to number of prior transurethral anastomotic strictures. CONCLUSIONS: We could not identify a reliable risk factor to predict development of anastomotic strictures following radical prostatectomy.

Open ureteroplasty with buccal mucosa graft for long proximal strictures: A good option for a rare problem.

Purpose: To report a single surgeon experience with one year follow-up after open ureteroplasty with buccal mucosa graft (OUBMG) in the rare situation of long segment proximal ureteral strictures. Materials and Methods: Four patients with long segment proximal ureteral stricture underwent OU-BMG between February and July 2017. Functional outcome was assessed by pre- and postoperative serum creatinine, ultrasound and renal scintigraphy as well as patient reported outcomes. Results: Four patients with an average stricture length of 4 cm underwent OU-BMG between February and July 2017. No major postoperative complications occurred. Retrograde uretero-pyelography 6 weeks postoperatively revealed a watertight anastomosis followed by immediate emptying of the renal pelvis and ureter in all four patients. Ureteroscopy at this time showed a wide lumen with well-vascularized pink mucosa. After a mean follow-up time of 12.5 (12-14) months, postoperative serum creatinine was unimpaired. Renal scintigraphy revealed no signs of renal obstruction. With regard to intraoral surgery, no difficulties with mouth opening or intraoral dryness or numbness were reported. Conclusions: For patients with long segment ureteral strictures OU-BMG is a safe technique with excellent surgical and functional outcomes. Hence, the application of this technique should be encouraged and regarded as one of the standard options in case of this rare problem.

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.

Salvage lymph node dissection after 68Ga-PSMA or 18F-FEC PET/CT for nodal recurrence in prostate cancer patients.

The management of patients with biochemical recurrence (BCR) after definitive treatment for prostate cancer remains controversial. Our aim was to determine survival rates and complications of salvage lymph node dissection (sLND) in patients with recurrent prostate cancer after radical prostatectomy, while evaluating biochemical response (BR) with two different positron emission tomography/computed tomography (PET/CT) tracers used for preoperative imaging. sLND was performed in 104 patients diagnosed with isolated nodal recurrence on either 18F-fluoroethylcholine (18F-FEC) or 68Ga-PSMA-HBED-CC (68Ga-PSMA) PET/CT. Surgical complications, BR, clinical recurrence (CR), and cancer-specific survival (CSS) were evaluated. Logistic regression was used to determine predictors of complete BR (cBR) and CR after sLND and survival rates were assessed. Median follow-up was 39.5 months. Median patient age and prostate-specific antigen (PSA) at sLND were 64 years and 4.1 ng/mL. Median number of lymph nodes (LNs) removed was 13; median number of positive LNs was 3 per patient. Rate of Clavien-Dindo Grade III complications was low (4.8%). 29.8% of patients developed cBR (PSA < 0.2 ng/mL), and 56.7% partial BR (PSA postoperative < PSA preoperative) after sLND. Patients with LN metastases diagnosed on 68Ga-PSMA PET/CT showed a higher rate of cBR compared to 18F-FEC PET/CT (45.7 vs. 21.7%, p = 0.040). PSA at sLND (p = 0.031) and choice of PET tracer (p = 0.048) were independent predictors of cBR. The 5-year BCR-free, CR-free and CSS rates were 6.2%, 26.0%, and 82.8%, respectively. While preoperative staging with 68Ga-PSMA seems superior, only a limited number of patients developed cBR after surgery. Most patients experienced BCR and CR during follow-up.

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.

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.

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.

A comparative assessment of prostate positioning guided by three-dimensional ultrasound and cone beam CT.

BACKGROUND: The accuracy of the Elekta Clarity™ three-dimensional ultrasound system (3DUS) was assessed for prostate positioning and compared to seed- and bone-based positioning in kilo-voltage cone-beam computed tomography (CBCT) during a definitive radiotherapy. METHODS: The prostate positioning of 6 patients, with fiducial markers implanted into the prostate, was controlled by 3DUS and CBCT. In total, 78 ultrasound scans were performed trans-abdominally and compared to bone-matches and seed-matches in CBCT scans. Setup errors detected by the different modalities were compared. Systematic and random errors were analysed, and optimal setup margins were calculated. RESULTS: The discrepancy between 3DUS and seed-match in CBCT was -0.2 ± 2.7 mm laterally, -1.9 ± 2.3 mm longitudinally and 0.0 ± 3.0 mm vertically and significant only in longitudinal direction. Using seed-match as reference, systematic errors of 3DUS were 1.3 mm laterally, 0.8 mm longitudinally and 1.4 mm vertically, and random errors were 2.5 mm laterally, 2.3 mm longitudinally, and 2.7 mm vertically. No significant difference could be detected for 3DUS in comparison to bone-match in CBCT. CONCLUSIONS: 3DUS is feasible for image guidance for patients with prostate cancer and appears comparable to CBCT based image guidance in the retrospective study. While 3DUS offers some distinct advantages such as no need of invasive fiducial implantation and avoidance of extra radiation, its disadvantages include the operator dependence of the technique and dependence on sufficient bladder filling. Further study of 3DUS for image guidance in a large patient cohort is warranted.

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.

Urethral stricture: etiology, investigation and treatments.

BACKGROUND: Urethral stricture is a narrowing of the urethra due to scar tissue, which leads to obstructive voiding dysfunction with potentially serious consequences for the entire urinary tract. Its prevalence among men in industrial countries is estimated at 0.9%. It produces obstructive and irritative urinary symptoms and can ultimately impair renal function. Urethral strictures can be caused by diagnostic or therapeutic urological procedures. These procedures are being performed ever more commonly, because the population is aging; thus, urethral strictures will probably become more common as well. METHODS: We selectively reviewed pertinent original articles and meta-analyses (1995-2012) on the causes, diagnostic evaluation, and treatment of urethral strictures, which were retrieved by a search in the PubMed database. RESULTS: Most of the relevant publications are reports of retrospective studies from single centers. Only a few prospective randomized trials and structured reviews are available. The overall level of the scientific evidence is low. 45% of urethral strictures are iatrogenic, 30% idiopathic, and 20% due to bacterial urethritis. Strictures are diagnosed with a flow test and a retrograde urethrogram. Short bulbar strictures can be treated endoscopically. For recurrent and complex strictures, only open urethral surgery can reliably and permanently remove the infravesical obstruction. CONCLUSION: Urethral strictures must be recognized and treated so that their most serious long-term complication, impaired renal function, can be prevented. The clinical utility of urethrotomy is limited by a high recurrence rate.

Ureterorenoscopic biopsy and urinary cytology according to the 2004 WHO classification underestimate tumor grading in upper urinary tract urothelial carcinoma.

OBJECTIVES: To determine accuracy of upper tract cytology and ureteroscopic biopsy according to the 2004 World Health Organization (WHO) classification in predicting the correct tumor grade in patients with urothelial cancer of the upper urinary tract (UUT-UC). METHODS: Pathology reports of 77 nephroureterectomy specimens were retrospectively analyzed for tumor grade and compared with preoperatively gained cytology and ureteroscopic biopsy results. For analysis, the 2004 WHO classification was used. RESULTS: Overall sensitivity of cytology and biopsy in diagnosis of UUT-UC was 64% and 74%, respectively. Accuracy of cytology and biopsy in predicting high grade cancer was 53% and 58%, respectively. Combination of cytology and biopsy could improve sensitivity (84%) and accuracy (68%), but even for this combination, 15% of high grade tumors were misinterpreted as low grade cancer. CONCLUSION: Our results show only limited accuracy for preoperative cytology and ureterorenoscopically performed biopsies in the prediction of the correct tumor grading of an UUT-UC. Therefore, we suggest the use of additional diagnostic procedures before the decision for definitive surgical treatment in patients with UUT-UC is made.

Interobserver variability limits exact preoperative staging by computed tomography in bladder cancer.

OBJECTIVE: To evaluate the agreement between radiologic staging of bladder cancer using multidetector row computed tomography (CT) and histopathologic staging and estimate the influence of interobserver variability of the CT findings as a potential limitation of this imaging modality. The available data on the value of multidetector row CT in clinical staging before cystectomy are controversial. METHODS: The multidetector row CT reports of all patients undergoing radical cystectomy at our institution from 2004 to 2008 were retrospectively reviewed and compared in a blinded expert review by an experienced abdominal/genitourinary radiologist. The results of both radiologic reviews were subsequently correlated with the pathologic findings of the surgical specimens. The interobserver variability of radiology reports was estimated using κ statistics. RESULTS: Preoperative CT scans were available for 276 patients who underwent radical cystectomy. The accuracy of the primary and reference radiologists in predicting the correct local tumor stage was 49% (κ 0.23, P < .001) and 51% (κ 0.24, P < .001), respectively. The accuracy in predicting the presence of lymph node metastases was 54% (κ 0.04, P = .297) and 58% (κ 0.15, P = .011). The agreement between both radiologists was fair with regard to the local tumor stage (κ 0.23, P < .001) and the presence of lymph node metastases (κ 0.35, P < .001). CONCLUSION: The overall agreement between the local bladder cancer stage between CT and pathologic staging was poor to fair. Significant interobserver variability was found in the CT findings that might contribute to the limited accuracy of CT in the detection of extravesical tumor spread, infiltration of extravesical organs, and lymph node involvement.

Predicting clinical outcomes after radical nephroureterectomy for upper tract urothelial carcinoma.

BACKGROUND: Novel prognostic factors for patients after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) have recently been described. OBJECTIVE: We tested the prognostic value of pathologic characteristics and developed models to predict the individual probabilities of recurrence-free survival (RFS) and cancer-specific survival (CSS) after RNU. DESIGN, SETTING, AND PARTICIPANTS: Our study included 2244 patients treated with RNU without neoadjuvant or adjuvant therapy at 23 international institutions. Tumor characteristics included T classification, grade, lymph node status, lymphovascular invasion, tumor architecture, location, and concomitant carcinoma in situ (CIS). The cohort was randomly split for development (12 centers, n=1273) and external validation (11 centers, n=971). INTERVENTIONS: All patients underwent RNU. MEASUREMENTS: Univariable and multivariable models addressed RFS, CSS, and comparison of discrimination and calibration with American Joint Committee on Cancer (AJCC) stage grouping. RESULTS AND LIMITATIONS: At a median follow-up of 45 mo, 501 patients (22.3%) experienced disease recurrence and 418 patients (18.6%) died of UTUC. On multivariable analysis, T classification (p for trend <0.001), lymph node metastasis (hazard ratio [HR]: 1.98; p=0.002), lymphovascular invasion (HR: 1.66; p<0.001), sessile tumor architecture (HR: 1.76; p<0.001), and concomitant CIS (HR: 1.33; p=0.035) were associated with disease recurrence. Similarly, T classification (p for trend<0.001), lymph node metastasis (HR: 2.23; p=0.001), lymphovascular invasion (HR: 1.81; p<0.001), and sessile tumor architecture (HR: 1.72; p=0.001) were independently associated with cancer-specific mortality. Our models achieved 76.8% and 81.5% accuracy for predicting RFS and CSS, respectively. In contrast to these well-calibrated models, stratification based upon AJCC stage grouping resulted in a large degree of heterogeneity and did not improve discrimination. CONCLUSIONS: Using standard pathologic features, we developed highly accurate prognostic models for the prediction of RFS and CSS after RNU for UTUC. These models offer improvements in calibration over AJCC stage grouping and can be used for individualized patient counseling, follow-up scheduling, risk stratification for adjuvant therapies, and inclusion criteria for clinical trials.

Macroscopic sessile tumor architecture is a pathologic feature of biologically aggressive upper tract urothelial carcinoma.

OBJECTIVE: Macroscopic sessile tumor architecture was associated with adverse outcomes after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Before inclusion in daily clinical decision-making, the prognostic value of tumor architecture needs to be validated in an independent, external dataset. We tested whether macroscopic tumor architecture improves outcome prediction in an international cohort of patients. MATERIAL AND METHODS: We retrospectively studied 754 patients treated with RNU for UTUC without neoadjuvant chemotherapy at 9 centers located in Asia, Canada, and Europe. Tumor architecture was macroscopically categorized as either papillary or sessile. Univariable and multivariable Cox regression analyses were used to address recurrence-free (RFS) and cancer-specific survival (CSS) estimates. RESULTS: Macroscopic sessile architecture was present in 20% of the patients. Its prevalence increased with advancing pathologic stage and it was significantly associated with established features of biologically aggressive UTUC, such as tumor grade, lymph node metastasis, lymphovascular invasion, and concomitant CIS (all P values < 0.02). The median follow-up for patients who were alive at last follow-up was 40 months (IQR: 18-75 months, range: 1-271 months). Two-year RFS and CSS for tumors with papillary architecture were 85% and 90%, compared with 58% and 66% for those with macroscopic sessile architecture, respectively (P values < 0.0001). On multivariable Cox regression analyses, macroscopic sessile architecture was an independent predictor of both RFS (hazard ratio {HR}: 1.5; P = 0.036) and CSS (HR: 1.5; P = 0.03). CONCLUSION: We confirmed the independent prognostic value of macroscopic tumor architecture in a large, independent, multicenter UTUC cohort. It should be reported in every pathology report and included in post-RNU predictive models in order to refine current clinical decision making regarding follow-up protocol and adjuvant therapy.