Genitourinary tumors.

Memorial Sloan Kettering Cancer Center (MSK) has made many notable contributions to the scientific understanding and care of patients with common urologic cancers. Many of the advances represented paradigm shifts in management and established new standards of care. This review highlights the surgical procedures and treatment strategies originated and pioneered by urologic surgeons and colleagues at MSK during the past 50 years.

The impact of repeat biopsies on infectious complications in men with prostate cancer on active surveillance.

PURPOSE: Prostate biopsy related infectious complications are associated with significant morbidity. The risk of infectious complications in patients with prostate cancer on active surveillance remains under studied. MATERIALS AND METHODS: A total of 591 consecutive men who underwent prostate biopsy were prospectively enrolled in a study evaluating prostate biopsy related complications between January 2011 and January 2012. Of these men 403 were previously diagnosed with prostate cancer and were included in this study. They underwent a 14-core transrectal ultrasound guided prostate biopsy as part of an active surveillance regimen. A nurse contacted all men within 14 days of biopsy, and information was collected on potential complications, antibiotics received and bacterial culture results. RESULTS: Fourteen patients (3.5%) had infectious complications including 13 requiring hospitalization. Five patients had positive urine cultures, and fluoroquinolone resistant isolates were identified in 4 patients, including 2 with extended spectrum beta-lactamase producing isolates. We evaluated the impact of risk factors including diabetes, benign prostatic hyperplasia and antibiotic regimen. However, only the number of previous prostate biopsies was significantly associated with an increased risk of infectious complications (p = 0.041). For every previous biopsy the odds of an infection increased 1.3 times (OR 1.33, 95% CI 1.01-1.74). CONCLUSIONS: In men with prostate cancer on active surveillance the number of previous prostate biopsies is associated with a significant risk of infectious complications and every previous biopsy increases the risk of infectious complication. Fluoroquinolone resistant and extended spectrum beta-lactamase producing isolates represent the most commonly identified organisms. Men with prostate cancer on active surveillance should be informed of the risks associated with serial repeat prostate biopsies.

Reoperative retroperitoneal surgery.

Although RPLND is both a diagnostic and therapeutic procedure, it must be performed with therapeutic intent. Adequacy of initial RPLND is a prognostic variable for clinical outcome. Effective cisplatin-based chemotherapy will not reliably compensate for suboptimal initial surgery. Many patients undergoing either primary RPLND or PC-RPLND will have unresected extratemplate disease if modified templates are used. Anatomic mapping studies, which provided the basis for modified templates, have significant limitations. Teratomatous elements are often found in the retroperitoneum of patients requiring reoperative surgery, which can be performed with acceptable morbidity in tertiary centers with experienced surgeons. The integration of chemotherapy and reoperative surgery can result in survival rates of almost 70% in patients with retroperitoneal relapse after initial suboptimal RPLND.

Phase I trial of intravesical gemcitabine in bacillus Calmette-Guérin-refractory transitional-cell carcinoma of the bladder.

PURPOSE: The aim of this phase I study was to determine the safety and toxicity profile of gemcitabine administered as an intravesical agent in patients with transitional-cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Patients with superficial bladder cancer refractory to intravesical bacillus Calmette-Guérin (BCG) therapy and refusing a cystectomy were considered eligible for the trial. Gemcitabine was given in the bladder for 1 hour twice weekly in 100 mL sodium chloride for a total of six treatments. After a 1-week break, a second course of six treatments over 3 weeks was given, followed by response assessment. Four dose levels were explored: 500 mg, 1,000 mg, 1,500 mg, and 2,000 mg. RESULTS: Eighteen patients completed therapy: three at 500 mg, six at 1,000 mg, three at 1,500 mg, and six at 2,000 mg. No grade 3 or 4 toxicity was observed at 500 mg. At 1,000 mg, three patients developed hematuria and one had a skin reaction resembling grade 3 hand-foot syndrome. Three patients at 1,500 mg had no grade 3 or 4 toxicity. Of six patients at 2,000 mg, one had grade 3 thrombocytopenia and neutropenia without infection. Seven patients had a complete response (negative cytology and posttreatment biopsy), and four patients had a mixed response (negative bladder biopsy but positive cytology). CONCLUSION: Gemcitabine has substantial activity as an intravesical agent in BCG-refractory TCC and warrants further investigation. Therapy given twice weekly was associated with minimal bladder irritation and tolerable myelosuppression. The recommended phase II dose for twice-weekly therapy is 2,000 mg.

Late relapse of testicular germ cell tumors.

The successful multidisciplinary approach for the management of germ cell tumors of the testis has resulted in survival rates of greater than 90% overall. While the majority of relapses in patients with germ cell tumors occur within the first 2 years of treatment, the incidence of late relapse beyond 2 years has been increasing over recent years. The pattern of late relapse suggests that an inadequately controlled retroperitoneum is a major predisposing factor, with up to 80% of late relapses occurring in the retroperitoneum. These tumors tend to be chemorefractory and overall prognosis for patients with late relapse of germ cell tumors is relatively poor, with survival rates of approximately 30% to 40%. In this review, we present the recent data regarding the clinical presentation, patterns of relapse, histologic findings, appropriate treatment options, and outcomes for men with late relapse of germ cell tumors.

Surgery for retroperitoneal relapse in the setting of a prior retroperitoneal lymph node dissection for germ cell tumor.

Recognition of the therapeutic role of retroperitoneal lymph node dissection (RPLND) in the setting of testicular germ cell tumors (GCTs) is of utmost importance. Although the histologic findings of RPLND provide diagnostic and prognostic information, the adequacy of initial RPLND is an independent predictor of clinical outcome. Despite the advent of effective cisplatin-based chemotherapy for testicular GCTs, patients who have undergone suboptimal surgery at the time of initial RPLND are compromised. Despite the initial enthusiasm surrounding anatomic mapping studies, the use of modified RPLND templates has the potential to leave a significant number of patients with unresected retroperitoneal disease. Teratomatous elements are particularly common. Patients with retroperitoneal relapse following initial RPLND should be treated with reoperative RPLND and chemotherapy and can expect long term survival rates nearing 70% when treated in tertiary centers by experienced surgeons.

Phase II trial of intravesical gemcitabine in bacille Calmette-Guérin-refractory transitional cell carcinoma of the bladder.

PURPOSE: The aim of this phase II study was to determine the efficacy of gemcitabine administered as an intravesical agent in patients with bacille Calmette-Guérin (BCG) -refractory transitional cell carcinoma of the bladder. PATIENTS AND METHODS: Patients with superficial bladder cancer refractory or intolerant to intravesical BCG therapy and refusing a cystectomy were considered eligible for the trial. Eligible patients received two courses of intravesical gemcitabine twice weekly at a dose of 2,000 mg/100 mL for 3 consecutive weeks, with each course separated by 1 week of rest. Patients were evaluated for response at 8 weeks, then every 3 months to 1 year. RESULTS: Thirty eligible patients were included on study. The median follow-up for all the patients was 19 months (range, 0 to 35 months). Of the 30 patients, 15 (50%; 95% CI, 32% to 68%) achieved a complete response (CR). Twelve patients had tumor recurrence with a median recurrence-free survival time of 3.6 months (95% CI, 2.9 to 11.0 months). Two patients maintained a CR at 23 and 29 months, respectively. The 1-year recurrence-free survival rate for patients with a CR was 21% (95% CI, 0% to 43%). Two patients progressed to a higher stage while receiving gemcitabine treatment. The median follow-up for patients who did not have a progression or a cystectomy was 19 months (range, 2 to 35 months). Eleven patients (37%) underwent a cystectomy subsequent to gemcitabine therapy. CONCLUSION: Gemcitabine has activity in a high-risk patient population and remains a viable option for some patients who refuse cystectomy.

Histology and clinical outcomes in patients with bilateral testicular germ cell tumors: the Memorial Sloan Kettering Cancer Center experience 1950 to 2001.

PURPOSE: The optimal management of bilateral testicular tumors continues to evolve. We examined the incidence, characteristics, histology, treatment and clinical outcomes of patients with bilateral testicular cancer. MATERIALS AND METHODS: Between 1950 and 2001, 3,984 patients with testicular cancer were treated at our center. A total of 58 patients with bilateral testicular germ cell tumors were identified. The clinical records of these 58 patients were reviewed for age, histology of the 2 tumors, stage at presentation of the first and second tumor, interval between tumors, treatment and clinical outcome. Median followup was 60 months. RESULTS: Ten of the 58 patients (17%) had synchronous tumors, while the other 48 (83%) had metachronous tumors with a median interval between tumors of 50.5 months. Overall seminoma was the most common histology of the synchronous and metachronous tumors. Most patients in the synchronous and metachronous tumor groups presented with low stage disease. Of the 58 patients 52 (89%) had no evidence of disease and 6 (11%) were dead of disease at the last followup. Treatment of the second tumor appeared to be influenced by therapy for the first tumor in 16.7% of cases. CONCLUSIONS: Patients with a history of testicular germ cell tumor require careful long-term monitoring of the contralateral testicle due to the risk of bilateral disease and potentially long latent period between the first and second tumors. Overall the clinical outcome is good in these patients when they are treated appropriately for histology and stage. In patients with metachronous tumors treatment of the contralateral tumor is rarely altered by prior treatment of the initial tumor.

Carcinoma in a bladder diverticulum: presentation and treatment outcome.

PURPOSE: In this retrospective review we characterize the outcomes of patients treated for transitional cell carcinoma in a bladder diverticulum. MATERIALS AND METHODS: Between 1986 and 2001, 39 patients were treated for tumors in a bladder diverticulum. All patients underwent initial transurethral resection of the tumor. Based on cystoscopic evaluation, bimanual examination and computerized tomography findings, tumors were classified as superficial (Ta, Tis), superficially invasive confined to diverticulum (T1) or extra diverticular (T3+). Patients with superficial or superficially invasive disease were treated either conservatively with repeat transurethral resection, or with partial or radical cystectomy. Patients with extra diverticular extension were treated with partial or radical cystectomy when amenable to surgical extirpation. Predictors of outcome were assessed by univariate and multivariate analyses. End point was overall and disease-specific survival. RESULTS: Of our cohort of 39 patients 13 (33%) presented with superficial disease, 13 (33%) with superficially invasive tumors and 13 (33%) with invasive (extra diverticular) disease. Actuarial 5-year disease specific survival for the cohort was 72 +/- 5.4%. Significant differences in 5-year disease specific survival were observed among patients presenting with superficial tumors (83 +/- 9%), superficially invasive tumors (67 +/- 7%) and extra diverticular disease (45 +/- 14%). Of the patients presenting with T1 tumors the primary mode of treatment did not correlate with outcome. In a multivariate model clinical staging was the only independent predictor of outcome and concomitant carcinoma in situ reached borderline significance. CONCLUSIONS: Our data support a conservative approach for tumors confined to the bladder diverticulum, provided complete removal is feasible and close surveillance ensues.

Comparisons of nomograms and urologists' predictions in prostate cancer.

When applying nomograms to a clinical setting it is essential to know how their predictions compare with clinicians'. Comparisons exist outside of the prostate cancer literature. We reviewed these comparisons and conducted 2 experiments comparing predictions of clinicians with prostate cancer nomograms. By using Medline, we searched studies from January 1966 to July 1999 that compared human predictions with nomogram predictions. Next, we conducted 2 experiments: (1) 17 urologists were presented with 10 case vignettes and asked to predict the 5-year recurrence-free probabilities for each patient; (2) case presentations of 63 prostate cancer patients (including full clinical histories with complete diagnostic data and surgical findings) were made to a group of 25 clinicians who were asked to predict organ-confined disease. We found 22 published studies comparing human experts with nomograms, greater than half (13 of 22) showed the nomogram performing above the level of the human expert. Our first experiment showed urologist modification of 165 nomogram predictions led to a decrease in prediction accuracy (c-index decreased from.67 to.55, P <.05). In our second experiment, clinician predictions of organ-confined disease were comparable to the nomogram (area under the receiver operating characteristic curve [AUC] 0.78 and 0.79, respectively). A mixed-model suggests the nomogram did not augment clinician prediction accuracy (doctor excess error 1.4%, P =.75, 95% confidence interval [CI]: -10.9% to 8.2%). Our data suggest that nomograms do not seem to diminish predictive accuracy and they may be of significant benefit in certain clinical decision making settings.

Partial cystectomy: a contemporary review of the Memorial Sloan-Kettering Cancer Center experience and recommendations for patient selection.

PURPOSE: Partial cystectomy is a bladder sparing procedure that has been used to treat invasive bladder cancer in highly selected patients. This study analyzes the outcomes of partial cystectomy in a contemporary cohort of patients to identify appropriate selection criteria for the procedure. MATERIALS AND METHODS: Records were reviewed for 58 patients with a primary bladder tumor who had undergone partial cystectomy at Memorial Sloan-Kettering Cancer Center from 1995 to 2001. Information was collected on tumor size, histology, location, presence of carcinoma in situ (CIS), multifocality, neoadjuvant treatment, clinical stage, pathological stage and disease status. RESULTS: For the 58 patients analyzed, overall 5-year survival was 69% with a mean followup of 33 months (range 1 to 83). Of the patients 43 (74%) are alive with an intact bladder, 39 (67%) are currently disease-free with an intact bladder and 32 (55%) have been continuously disease-free with an intact bladder. Seven patients experienced a superficial recurrence and were treated successfully while 15 patients experienced an advanced recurrence. On univariate analysis CIS and multifocality were related to superficial recurrence, and lymph node involvement and positive surgical margin were related to advanced recurrence. On multivariate analysis concomitant CIS (odds ratio 7.05, p = 0.004) and lymph node involvement (odds ratio 4.38, p = 0.031) were predictors of advanced recurrence. CONCLUSIONS: In highly selected patients with invasive bladder cancer, partial cystectomy offers acceptable outcomes. Concomitant CIS and presence of metastases to regional lymph nodes predict advanced recurrence.

Bladder cancer as a prognostic factor for upper tract transitional cell carcinoma.

PURPOSE: Upper tract transitional cell carcinoma (UTTCC) is a relatively rare tumor. Overall 5-year disease specific survival is in the range of 16.5% to 95% depending on stage. In this study we evaluated predictors associated with disease recurrence and disease specific survival. MATERIALS AND METHODS: We report on 129 patients with a median age of 68 years who underwent nephroureterectomy for UTTCC between July 1989 and June 2002. A total of 67 patients had primary UTTCC and 62 had previous (52) or synchronous (10) transitional cell carcinoma of the bladder (BTCC). Medical records were reviewed and analyzed for possible prognostic predictors (primary tumor stage, grade, multifocality, carcinoma in situ, symptoms and signs at presentation, sex, and history of smoking). Disease specific survival and freedom from bladder recurrence were assessed with the Kaplan-Meier method, and differences between the groups were compared using the log rank test. The Cox proportional hazards regression model was used to assess the significance of each predictor. RESULTS: Disease specific death was reported for 44 patients. In a multivariate analysis using previous BTCC as a predictor (categorized as superficial, invasive or none), primary disease stage and history of BTCC were associated with disease specific survival (p = 0.001 and p = 0.018). History of BTCC grouped the patients into distinct populations in terms of disease specific survival and freedom from bladder recurrence. CONCLUSIONS: This study demonstrates that a history of BTCC (invasive or superficial) has an adverse effect on the prognosis of patients diagnosed with UTTCC independent of primary tumor stage.