D. Frohneberg

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.

The Ileal Neobladder: Experience and Results of more than 100 Consecutive Cases

AbstractThe ileal neobladder produces a completely detubularized, low pressure, high capacity reservoir constructed from ileum without any valves. From April 1986 through May 1989, 113 patients underwent this procedure at our institution. Of these patients 99 underwent simultaneous radical cystectomy for bladder cancer and 14 underwent bladder augmentation. The mean postoperative followup was 14.4 months, with a range of 1 to 36 months. There was no perioperative mortality. However, 7 patients died more than 2 months postoperatively: 5 of tumor progression, 1 of pneumonia and severe metabolic acidosis, and 1 of septicemia of unknown cause. Reoperation was necessary in only 13 patients; 10 patients required urethrotomy or dilation of urethral strictures. Day and night continence was preserved in 82.1% of all patients. Stress incontinence, which must be corrected by an artificial sphincter, was found in 4 patients (4.2%) and night-time incontinence that required an external device occurred in 5 (5.3%). Eigh...

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.

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.

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.

Bladder Carcinoma during Pregnancy

Introduction: We report 3 cases of bladder cancer during pregnancy and give a review of the literature in an attempt to evaluate tumor at presentation, characteristics, maternal and fetal outcome. Materials and Methods: The case history of 3 pregnant women treated for bladder cancer in 2001 together with the results of a MEDLINE search from 1966 to 2003. Results: Out of 27 cases of nonbilharzial bladder carcinoma, 74% presented with transitional cell carcinoma. Five patients had muscle-invasive tumors. Major symptom was hematuria in 81%, which was initially mistaken as vaginal bleeding in 22%. Only half of the tumors were identified by ultrasonography. Although superficial bladder carcinoma was transurethrally resected alone, outcome and prognosis are good. But the prognosis of locally advanced bladder carcinoma is poor. None of the fetuses delivered before 30 weeks of gestation survived. Two of the 5 patients died from the disease and follow-up is only short in the rest. Conclusion: Any doubtful genital bleeding during pregnancy without definite proof of vaginal/cervical origin should be investigated by both ultrasonography of the upper urinary tract and urethrocystoscopy. Superficial bladder tumors can be most effectively treated by transurethral resection followed by cystoscopy, whereas the prognosis of muscle-invasive bladder carcinoma is poor and demands more radical treatment, depending on the stage of pregnancy.

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

Study Type – Prognosis (retrospective cohort)

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.

Transplantation of a free peritoneal patch in surgery of the renal pelvis and ureter.

Operations on the urinary collecting system successfully utilized the free peritoneal patch in a variety of situations, as animal experiments have shown. When used to cover defects the peritoneum works as a multipotent matrix for invasion of urothelium; when used as an envelope it prevents stricture due to perihilar/periureteral scarring. We used a free peritoneal patch in 31 operations on the renal pelvis and ureter between 1975 and 1980. The indications for the patch were; defects of the renal pelvis of ureteropelvic junction due to surgery for recurring stones or carcinoma of the pelvis; and pyelocalicotomy of an intrarenal pelvis if it was impossible to suture the pelvis. We also used the patch to envelop renal pelvis and ureter in extended perihilar inflammation or stenosis of the pyeloureteral junction and proximal ureter due to scarring. The results, as shown by urography, were excellent or good in 25 or the 31 cases. The transplantation of a free peritoneal patch is a simple, reliable technique that can be recommended for covering defects or preventing stricture in surgery of the renal pelvis and ureter.