Functional Outcome and Complications following Ileal Neobladder Reconstruction in Male Patients without Tumor Recurrence. More than 35 Years of Experience from a Single Center.

PURPOSE: There is a lack of data on true long-term functional outcome of orthotopic bladder substitution. The primary study objective was to report our 35-year clinical experience. MATERIALS AND METHODS: Since October 1985, 259 male patients from a large single center radical cystectomy series with complete followup of more than 60 months (median 121, range 60-267) without recurrence, irradiation or undiversion that might have affected the functional outcome, were included. RESULTS: Median age at radical cystectomy and at survey was 63 (range 23-81) and 75 (range 43-92) years, respectively. Overall 87% of patients voided spontaneously and residual-free. This rate decreased with increasing age at the time of surgery (less than 50 years old 94%, 70 years old or older 82%). Overall day/nighttime continence rates were 90%/82%. These rates decreased with increasing age at the time of surgery from 100%/88% to 87%/80%. The overall pad-free rate was 71%/47%. Bicarbonate use decreased from 51% (5 years) to 19% (25 years). Patients with a followup of more than 20 years had the lowest rate of residual urine and clean intermittent catheterization (0.0%) as well as use of more than 1 pad at daytime/nighttime (6.3%/12.5%) and mucus obstruction (0.0%). Serum creatinine showed only the age related increase. The surgical complication rate was 27% and correlated inversely with functional results (chi-squared 11.227, p <0.005), even when the younger age at the time of surgery (younger than 60 years) was related to higher rates of surgical complications (chi-squared 6.80, p <0.05). CONCLUSIONS: The ileal neobladder represents an excellent long-term option for urinary diversion with an acceptable complication rate.

Extended Versus Limited Lymph Node Dissection in Bladder Cancer Patients Undergoing Radical Cystectomy: Survival Results from a Prospective, Randomized Trial.

BACKGROUND: The extent of lymph node dissection (LND) in bladder cancer (BCa) patients at the time of radical cystectomy may affect oncologic outcome. OBJECTIVE: To evaluate whether extended versus limited LND prolongs recurrence-free survival (RFS). DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter, phase-III trial patients with locally resectable T1G3 or muscle-invasive urothelial BCa (T2-T4aM0). INTERVENTION: Randomization to limited (obturator, and internal and external iliac nodes) versus extended LND (in addition, deep obturator, common iliac, presacral, paracaval, interaortocaval, and para-aortal nodes up to the inferior mesenteric artery). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was RFS. Secondary endpoints included cancer-specific survival (CSS), overall survival (OS), and complications. The trial was designed to show 15% advantage of 5-yr RFS by extended LND. RESULTS AND LIMITATIONS: In total, 401 patients were randomized from February 2006 to August 2010 (203 limited, 198 extended). The median number of dissected nodes was 19 in the limited and 31 in the extended arm. Extended LND failed to show superiority over limited LND with regard to RFS (5-yr RFS 65% vs 59%; hazard ratio [HR]=0.84 [95% confidence interval 0.58-1.22]; p=0.36), CSS (5-yr CSS 76% vs 65%; HR=0.70; p=0.10), and OS (5-yr OS 59% vs 50%; HR=0.78; p=0.12). Clavien grade ≥3 lymphoceles were more frequently reported in the extended LND group within 90d after surgery. Inclusion of T1G3 tumors may have contributed to the negative study result. CONCLUSIONS: Extended LND failed to show a significant advantage over limited LND in RFS, CSS, and OS. A larger trial is required to determine whether extended compared with limited LND leads to a small, but clinically relevant, survival difference (ClinicalTrials.gov NCT01215071). PATIENT SUMMARY: In this study, we investigated the outcome in bladder cancer patients undergoing cystectomy based on the anatomic extent of lymph node resection. We found that extended removal of lymph nodes did not reduce the rate of tumor recurrence in the expected range.

[Acute scrotal pain in childhood: legal pitfalls]. / Das akute Scrotum im Kindesalter ­ Juristische Fallstricke.

Acute scrotal pain in childhood is an emergency.Sudden scrotal pain may be caused by a variety of diseases. Therefore, it is important to carefully consider the specific medical history and possible differential diagnoses in each case for fast and decisive action (e. g. in case of testicular torsion). As minors lack the capacity for consent, it is absolutely necessary to obtain consent from their legal guardian. However, obtaining consent in the available time frame can cause organisational challenges in an acute emergency, which may lead to situations in the daily routine where a therapeutic decision needs to be taken (including surgery) without legal security based on consent by the guardian. In some cases, the child's consent also needs to be taken into account, depending on its age and development.For the physician and surgeon in charge, the legal evaluation of the case at hand and therewith the obtainment of legal security are of great significance.

Outcome predictors of radical cystectomy in patients with cT4 prostate cancer: a multi-institutional study of 62 patients.

OBJECTIVES: To identify which patients with macroscopic bladder-infiltrating T4 prostate cancer (PCa) might have favourable outcomes when treated with radical cystectomy (RC). MATERIALS AND METHODS: We evaluated 62 patients with cT4cN0-1 cM0 PCa treated with RC and pelvic lymph node dissection between 1972 and 2011. In addition to descriptive statistics, the Kaplan-Meier method and log-rank tests were used to depict survival rates. Univariate and multivariate Cox regression analysis tested the association between predictors and progression-free, PCa-specific and overall survival. RESULTS: Of the 62 patients, 19 (30.6%) did not have clinical progression during follow-up, two (3.2%) had local recurrence, and 32 (51.6%) had haematogenous and nine (14.5%) combined pelvic and distant metastasis. Forty patients (64.5%) died, 34 (54.8%) from PCa and six (9.7%) from other causes. The median (range) survival time of the 19 patients who were metastasis-free at last follow-up was 86 (1-314) months, 8/19 patients had a follow-up of >5 years, and five patients survived metastasis-free for >15 years. Patients without seminal vesicle invasion (SVI) had the best outcomes, with an estimated 10-year PCa-specific survival of 75% compared with 24% for patients with SVI. CONCLUSION: For cT4 PCa RC can be an appropriate treatment for local control and part of a multimodality-treatment approach. Although recurrences are probable, these do not necessarily translate into cancer-specific death. Men without SVI had a 75% 10-year PCa-specific survival. Although outcomes for patients with SVI are not as favourable, there can be good local control; however, these patients are at higher risk of progression and may need more aggressive systemic treatment.

Natural history of surgically treated high-risk prostate cancer.

BACKGROUND: No data exist on the patterns of biochemical recurrence (BCR) and their effect on survival in patients with high-risk prostate cancer (PCa) treated with surgery. The aim of our investigation was to evaluate the natural history of PCa in patients treated with radical prostatectomy (RP) alone. MATERIALS AND METHODS: Overall, 2,065 patients with high-risk PCa treated with RP at 7 tertiary referral centers between 1991 and 2011 were identified. First, we calculated the probability of experiencing BCR after surgery. Particularly, we relied on conditional survival estimates for BCR after RP. Competing-risks regression analyses were then used to evaluate the effect of time to BCR on the risk of cancer-specific mortality (CSM). RESULTS: Median follow-up was 70 months. Overall, the 5-year BCR-free survival rate was 55.2%. Given the BCR-free survivorship at 1, 2, 3, 4, and 5 years, the BCR-free survival rates improved by+7.6%,+4.1%,+4.8%,+3.2%, and+3.7%, respectively. Overall, the 10-year CSM rate was 14.8%. When patients were stratified according to time to BCR, patients experiencing BCR within 36 months from surgery had higher 10-year CSM rates compared with those experiencing late BCR (19.1% vs. 4.4%; P<0.001). At multivariate analyses, time to BCR represented an independent predictor of CSM (P<0.001). CONCLUSIONS: Increasing time from surgery is associated with a reduction of the risk of subsequent BCR. Additionally, time to BCR represents a predictor of CSM in these patients. These results might help provide clinicians with better follow-up strategies and more aggressive treatments for early BCR.

Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

BACKGROUND: Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. OBJECTIVE: To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. INTERVENTION: Retropubic RP and pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. RESULTS AND LIMITATIONS: In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. CONCLUSIONS: These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. PATIENT SUMMARY: Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment.

Stratification of high-risk prostate cancer into prognostic categories: a European multi-institutional study.

BACKGROUND: High-risk prostate cancer (PCa) is an extremely heterogeneous disease. A clear definition of prognostic subgroups is mandatory. OBJECTIVE: To develop a pretreatment prognostic model for PCa-specific survival (PCSS) in high-risk PCa based on combinations of unfavorable risk factors. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective multicenter cohort study including 1360 consecutive patients with high-risk PCa treated at eight European high-volume centers. INTERVENTION: Retropubic radical prostatectomy with pelvic lymphadenectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Two Cox multivariable regression models were constructed to predict PCSS as a function of dichotomization of clinical stage (< cT3 vs cT3-4), Gleason score (GS) (2-7 vs 8-10), and prostate-specific antigen (PSA; ≤ 20 ng/ml vs > 20 ng/ml). The first "extended" model includes all seven possible combinations; the second "simplified" model includes three subgroups: a good prognosis subgroup (one single high-risk factor); an intermediate prognosis subgroup (PSA >20 ng/ml and stage cT3-4); and a poor prognosis subgroup (GS 8-10 in combination with at least one other high-risk factor). The predictive accuracy of the models was summarized and compared. Survival estimates and clinical and pathologic outcomes were compared between the three subgroups. RESULTS AND LIMITATIONS: The simplified model yielded an R(2) of 33% with a 5-yr area under the curve (AUC) of 0.70 with no significant loss of predictive accuracy compared with the extended model (R(2): 34%; AUC: 0.71). The 5- and 10-yr PCSS rates were 98.7% and 95.4%, 96.5% and 88.3%, 88.8% and 79.7%, for the good, intermediate, and poor prognosis subgroups, respectively (p = 0.0003). Overall survival, clinical progression-free survival, and histopathologic outcomes significantly worsened in a stepwise fashion from the good to the poor prognosis subgroups. Limitations of the study are the retrospective design and the long study period. CONCLUSIONS: This study presents an intuitive and easy-to-use stratification of high-risk PCa into three prognostic subgroups. The model is useful for counseling and decision making in the pretreatment setting.

The role of adjuvant hormonal treatment after surgery for localized high-risk prostate cancer: results of a matched multiinstitutional analysis.

Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5-10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.

Identifying the best candidate for radical prostatectomy among patients with high-risk prostate cancer.

BACKGROUND: The current role of radical prostatectomy (RP) in patients with high-risk disease remains controversial. OBJECTIVE: To identify which high-risk prostate cancer (PCa) patients might have favorable pathologic outcomes when surgically treated. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 1366 patients with high-risk PCa (ie, at least one of the following risk factors: prostate-specific antigen [PSA]>20 ng/ml, cT3, biopsy Gleason 8-10) treated with RP and pelvic lymph node dissection (PLND) at eight European centers between 1987 and 2009. A favorable pathologic outcome was defined as specimen-confined (SC) disease-namely, pT2-pT3a, node negative PCa with negative surgical margins. INTERVENTION: All patients underwent radical retropubic prostatectomy and PLND. MEASUREMENTS: Univariable and multivariable logistic regression models tested the association between predictors and SC disease. A logistic regression coefficient-based nomogram was developed and internally validated using 200 bootstrap resamples. The Kaplan-Meier method was used to depict biochemical recurrence (BCR) and cancer-specific survival (CSS) rates. RESULTS AND LIMITATIONS: Overall, 505 of 1366 patients (37%) had SC disease at RP. All preoperative variables (ie, age and PSA at surgery, clinical stage, and biopsy Gleason sum) were independent predictors of SC PCa at RP (all p≤0.04). Patients with SC disease had significantly higher 10-yr BCR-free survival and CSS rates than patients without SC disease at RP (66% vs 47% and 98 vs 88%, respectively; all p<0.001). A nomogram including PSA, age, clinical stage, and biopsy Gleason sum demonstrated 72% accuracy in predicting SC PCa. This study is limited by its retrospective design and by the lack of an external validation of the nomogram. CONCLUSIONS: Roughly 40% of patients with high-risk PCa have SC disease at final pathology. These patients showed excellent long-term outcomes when surgically treated, thus representing the ideal candidates for RP as the primary treatment for PCa. Prediction of such patients is possible using a nomogram based on routinely available clinical parameters.

Is there a prostate-specific antigen upper limit for radical prostatectomy?

OBJECTIVE: • To assess the feasibility of radical prostatectomy (RP) in a series of patients with prostate cancer with very high prostate-specific antigen (PSA) levels by comparing the clinical outcomes of different PSA thresholds (20.1-50 ng/mL, 50.1-100 ng/mL and >100 ng/mL, respectively). PATIENTS AND METHODS: • Within a multicentre European retrospective database of 712 RP in patients with a baseline PSA level >20 ng/mL, we identified 48 patients with prostate cancer with a preoperative PSA level >100 ng/mL, 137 with a PSA level between 50.1 and 100 ng/mL and 527 with PSA values between 20.1 and 50 ng/mL. • Comparisons between groups were performed using chi-square test, analysis of variance and Kaplan-Meier analysis with log-rank test. RESULTS: • Ten-year projected cancer-specific survival (79.8% in the PSA >100 ng/mL group vs 85.4% in the PSA 50.1-99 ng/mL group vs 90.9% in the PSA 20.1-50 ng/mL interval; P = 0.037) but not overall survival (59.6% in the PSA >100 ng/mL group vs 71.8% in the PSA 50.1-99 ng/mL group vs 75.3% in the PSA 20.1-50 ng/mL interval; P = 0.087) appeared significantly affected by the different PSA thresholds. • At a median follow-up of 78.7 months, 25.8%, 6.6% and 8.3% of patients in the PSA level groups for 20.1-50 ng/mL, 50.1-100 ng/mL and >100 ng/mL respectively, were cured by surgery alone. CONCLUSIONS: • Ten-year cancer-specific survival, while showing significant reduction with increasing PSA values intervals, remain relatively high even for PSA levels >100 ng/mL. • As part of a multimodal treatment strategy, RP may therefore be an option, even in selected patients with prostate cancer whose PSA level is >100 ng/mL.

Long-term outcome of patients with high-risk prostate cancer following radical prostatectomy and stage-dependent adjuvant androgen deprivation.

PURPOSE: To present the long-term outcome of high-risk prostate cancer patients treated by radical retropubic prostatectomy (RRP) and stage-dependent adjuvant androgen deprivation therapy. PATIENTS AND METHODS: Between 1989 and 2005, 2,655 patients underwent RRP by 9 surgeons. All cases (n = 372) with high-risk prostate cancer (serum PSA >20 ng/ml, and/or clinical stage T2c or greater, and/or biopsy Gleason score 8 or greater) were identified and analyzed retrospectively. RESULTS: At 5 and 10 years, cancer-specific survival was 91.3 and 87.2%; overall survival was 84.3 and 72.1%; biochemical progression-free survival (BPFS) was 76.6 and 56.2%; clinical progression-free survival was 86.2 and 79.9%. Kaplan-Meier analysis showed significant differences with respect to pathological stage and Gleason score for cancer-specific survival, BPFS and clinical progression-free survival. In multiple analysis, the only preoperative predictor of BPFS at the 5% level was clinical stage (p = 0.0055). CONCLUSION: In patients with high-risk prostate cancer and a life expectancy of more than 10 years, RRP with stage-dependent adjuvant androgen deprivation therapy is a viable alternative to radiation therapy.

Outcome predictors of radical prostatectomy in patients with prostate-specific antigen greater than 20 ng/ml: a European multi-institutional study of 712 patients.

BACKGROUND: Prostate cancer (PCa) patients with pretreatment prostate-specific antigen (PSA) >20 ng/ml have a high risk of biochemical and clinical failure and even cancer-related death after local therapy. Pretreatment predictors of outcome after radical prostatectomy (RP) in this patient group are necessary. OBJECTIVE: Our aim was to assess how the use of additional high-risk factors (biopsy Gleason score [bGS] > or = 8 or clinical stage 3-4) can improve prediction of treatment failure and cancer-related death after RP in patients with PSA >20. DESIGN, SETTING, AND PARTICIPANTS: In a retrospective multicentre cohort study from six European centres between 1987 and 2005, 712 patients with PSA >20 ng/ml underwent RP and bilateral pelvic lymphadenectomy. MEASUREMENTS: Subgroups were analysed to determine the relationship between the number of high-risk factors and histopathology, biochemical progression-free survival, clinical evidence of progressive disease, prostate cancer-specific mortality (PCSM), and overall mortality. Kaplan-Meier analysis with log-rank test and Cox multivariable analysis were applied. RESULTS AND LIMITATIONS: Median follow-up was 77 mo. The number of high-risk factors was significantly associated with unfavourable histopathology. Among patients with only PSA >20 ng/ml, 33% had pT2 PCa, 57.9% had bGS <7, 54% had negative surgical margins, and 85% were lymph node negative (pN0), whereas among patients with all three high-risk factors, 4.5% had pT2 PCa, 2.3% had bGS <7, 20.5% had negative margins, and 49% were pN0 (p<0.001). The strongest predictor of progression and mortality was bGS. PSA >20 ng/ml associated with bGS < or =7 resulted in 10-yr PCSM of 5%; when associated with bGS > or =8, PCSM was 35%. The main limitations of the study were retrospective design and varying treatment modalities. CONCLUSIONS: PCa patients with PSA >20 ng/ml have varying risk levels of disease progression and PCSM. Considering additional risk factors further stratifies this group into four subgroups that can guide the clinician in preoperative patient counselling.

Adjuvant cisplatin plus methotrexate versus methotrexate, vinblastine, epirubicin, and cisplatin in locally advanced bladder cancer: results of a randomized, multicenter, phase III trial (AUO-AB 05/95).

PURPOSE: Radical cystectomy as standard treatment of muscle-invasive urothelial carcinoma of the urinary bladder cures less than 50% of patients with locally advanced bladder cancer. We compared two adjuvant combination chemotherapies in patients with stage pT3a-4a and/or pathologic node-positive transitional-cell carcinoma of the bladder after radical cystectomy. PATIENTS AND METHODS: A total of 327 patients were randomly assigned to either adjuvant systemic chemotherapy with three cycles of cisplatin 70 mg/qm(2) on day 1 and methotrexate 40 mg/qm(2) on days 8 and 15 of a 21-day cycle (CM) or three cycles of methotrexate 30 mg/qm(2) on days 1, 15, and 22, vinblastine 3 mg/qm(2) on days 2, 15, and 22, epirubicin 45 mg/qm(2) on day 2, and cisplatin 70 mg/qm(2) on day 2 of a 28-day cycle (M-VEC). RESULTS: The hazard ratio for progression-free survival as the primary end point was 1.13 (90% CI, 0.86 to 1.48) for 163 CM patients compared with 164 M-VEC patients whose right-hand limit remained below the upper bound compatible with the noninferiority hypothesis (alpha = .0403). The 5-year progression-free, tumor-specific, and overall survival rates (point estimates +/- SE) for CM versus M-VEC were 46.3% +/- 4.6% v 48.8% +/- 4.5%, 52.0% +/- 4.6% v 52.3% +/- 4.8%, and 46.1% +/- 4.3% v 45.1% +/- 4.6%, respectively. WHO grade 3 and 4 leukopenia occurred in 7.0% of patients treated with CM and 22.2% of patients treated with M-VEC (P < .0001). CONCLUSION: CM cannot be considered inferior to M-VEC with regard to progression-free survival of patients with locally advanced bladder cancer after radical cystectomy. Moreover, patients receiving adjuvant CM combination therapy experienced significantly less grade 3 and 4 leukopenia than patients treated with M-VEC.