John S. Lam

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSE To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. RESULTS The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. CONCLUSION This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

Flexible Ureteroscopy and Laser Lithotripsy for Single Intrarenal Stones 2 cm or Greater—Is This the New Frontier?

PURPOSE Percutaneous nephrolithotomy has been the standard of care for intrarenal calculi greater than 2 cm. Flexible ureteroscopy with holmium laser lithotripsy is a minimally invasive treatment modality that is able to treat large intrarenal calculi with the potential to decrease morbidity, while maintaining a high level of efficacy. MATERIALS AND METHODS A total of 15 patients with a single intrarenal calculus 2 cm or greater were treated with retrograde ureteroscopic nephrolithotripsy. Lithotripsy was performed with a 7.2Fr flexible ureteroscope and 200 micron laser fiber. The stone-free rate was defined as the absence of any stones in the kidney or residual stone fragments less than 1 mm, which is too small to be extracted with a basket or a grasper. All patients underwent followup ureteroscopy within 15 days after the last procedure and renal ultrasound 30 days after the last treatment. RESULTS There were a total of 15 intrarenal calculi 20 to 25 mm (mean 22) in diameter. The mean number of procedures was 2.3 (range 2 to 4). The overall stone-free rate was 93.3%. One patient (6.6%) had a residual 5 mm stone fragment in the lower pole of the kidney, which was followed expectantly for 2 years with no change in size. There were no major complications. There were 3 minor complications (20%), including 1 emergency room visit for fever and pain, and 2 cases of gross hematuria. All cases were performed on an outpatient basis. CONCLUSIONS In select patients with a single intrarenal calculus 2 cm or greater small diameter flexible ureteroscopy with holmium laser lithotripsy may represent an alternative therapy to standard percutaneous nephrolithotomy with acceptable efficacy and low morbidity.

Prostate Stem Cell Antigen Is Overexpressed in Prostate Cancer Metastases

Purpose: Prostate stem cell antigen (PSCA) is expressed by a majority of prostate cancers and is a promising therapeutic target. PSCA protein and mRNA expression was examined in prostate cancer bone, lymph node, and visceral metastases to assess the potential of PSCA as an immunotherapeutic target in advanced prostate cancer. Experimental Design: Immunohistochemical analysis of PSCA protein expression and quantitative mRNA expression analysis of PSCA was done on clinical specimens of prostate cancer bone, lymph node, and visceral metastases. PSCA protein and mRNA expression levels were quantified and compared between available matched pairs of bone and lymph node or visceral metastases. Results: Bone metastases stained with higher intensity of PSCA compared with lymph node or liver metastases in seven of eight (87.5%) matched pairs (P = 0.035). PSCA mRNA expression was equal or greater than that of LAPC-9, a PSCA expressing xenograft, in 12 of 24 (50%) cases of prostate cancer metastases and was significantly correlated with PSCA protein expression (σ = 0.84, P = 0.0019). Overall, PSCA protein expression was detected in 41 of 47 (87.2%), four of six (66.7%), and two of three (66.7%) cases of bone, lymph node, and liver metastases, respectively. Mean PSCA staining intensity was significantly higher in prostate cancer bone metastases compared with lymph node metastases (2.0 ± 0.02 versus 0.83 ± 0.31, P = 0.014). Conclusions: Prostate cancer metastases express PSCA. However, greater PSCA staining intensity and level of PSCA mRNA expression was associated with bone metastases compared with lymph node metastases. This study suggests that PSCA is a promising tumor marker and potential therapeutic target for patients with metastatic prostate cancer.

Novel approaches in the therapy of metastatic renal cell carcinoma

Renal cell carcinoma (RCC) is the most lethal of the common urologic malignancies, with approximately 40% of patients eventually dying of cancer progression. Approximately one third of patients present with metastatic disease, and up to 40% treated for localized disease have a recurrence. Recent advances in the understanding of the pathogenesis, behavior, and molecular biology of RCC have paved the way for developments that may enhance early diagnosis, better predict tumor prognosis, and improve survival for RCC patients. The recent discovery of molecular tumor markers is expected to revolutionize the staging of RCC in the future and lead to the development of new therapies based on molecular targeting. Cytokine-based immunotherapy can be considered standard therapy in the treatment of metastatic RCC today. However, new therapies such as tumor vaccines, anti-angiogenesis agents, and small molecule inhibitors are being developed to improve efficacy and treat those patients who are unable to tolerate or are resistant to systemic immunotherapy. The aim of this review is to provide an update on current therapeutic approaches and targeted molecular therapy for metastatic RCC.

Treatment of proximal ureteral calculi: holmium:YAG laser ureterolithotripsy versus extracorporeal shock wave lithotripsy.

PURPOSE We compared the safety and efficacy of ureteroscopy with intracorporeal holmium:YAG laser lithotripsy and extracorporeal shock wave lithotripsy (ESWL) (Dornier Medical Systems, Inc., Marietta, Georgia) for proximal ureteral calculi. MATERIALS AND METHODS A total of 67 patients underwent 81 primary procedures, including in situ ESWL with a DoLi 50 lithotriptor (Dornier Medical Systems, Inc.) or ureteroscopy combined with holmium:YAG laser lithotripsy for proximal ureteral calculi. RESULTS Of the primary procedures 81 involved proximal ureteral calculi, including 35 done for calculi 1 cm. or greater. The initial stone-free rate in patients with calculi 1 cm. or greater was 93% for ureteroscopy combined with holmium:YAG laser lithotripsy and 50% for in situ ESWL. The efficiency quotient for treating proximal ureteral calculi 1 cm. or greater was calculated as 0.76 for ureteroscopic lithotripsy and 0.43 for ESWL. For proximal ureteral calculi less than 1 cm. the initial stone-free rate was 100% and 80% for ureteroscopic laser lithotripsy and ESWL, respectively. The efficiency quotient was calculated as 0.81 for ureteroscopic lithotripsy and 0.72 for ESWL for treating proximal ureteral calculi less than 1 cm. There were no major complications in either group and all procedures were performed on an outpatient basis. CONCLUSIONS Our study demonstrates that ureteroscopy combined with holmium:YAG laser lithotripsy is an acceptable treatment modality for all proximal ureteral calculi and excellent results are achieved for calculi 1 cm. or larger. Although the stone-free rate was better for smaller stones with ureteroscopic laser lithotripsy, efficiency quotients were similar. Therefore, ESWL should remain first line therapy for proximal ureteral calculi less than 1 cm. because of less morbidity, and a lesser anesthesia and analgesic requirement.

Secondary Hormonal Therapy for Advanced Prostate Cancer

PURPOSE Androgen ablation remains the cornerstone of management for advanced prostate cancer. Therapeutic options in patients with progressive disease following androgen deprivation include antiandrogen withdrawal, secondary hormonal agents and chemotherapy. Multiple secondary hormonal agents have clinical activity and the sequential use of these agents may lead to prolonged periods of clinical response. We provide a state-of-the-art review of the various agents currently used for secondary hormonal manipulation and discusses their role in the systemic treatment of patients with prostate cancer. MATERIALS AND METHODS A comprehensive review of the peer reviewed literature was performed on the topic of secondary hormonal therapies, including oral antiandrogens, adrenal androgen inhibitors, corticosteroids, estrogenic compounds, gonadotropin-releasing hormone antagonists and alternative hormonal therapies for advanced prostate cancer. RESULTS Secondary hormonal therapies can provide a safe and effective treatment option in patients with AIPC. The use of steroids and adrenolytics, such as ketoconazole and aminoglutethimide, has resulted in symptomatic improvement and a greater than 50% prostate specific antigen decrease in a substantial percent of patients with AIPC. A similar clinical benefit has been demonstrated with estrogen based therapies. Furthermore, these therapies have demonstrated a decrease in metastatic disease burden. Other novel hormonal therapies are currently under investigation and they may also show promise as secondary hormonal therapies. Finally, guidelines from the United States Food and Drug Administration Prostate Cancer Endpoints Workshop were reviewed in the context of developing new agents. CONCLUSIONS Secondary hormonal therapy serves as an excellent therapeutic option in patients with AIPC in whom primary hormonal therapy has failed. Practicing urologists should familiarize themselves with these oral medications, their indications and their potential side effects.

Preventing reservoir calculi after augmentation cystoplasty and continent urinary diversion: the influence of an irrigation protocol

One of the problems associated with bowel reservoirs is the development of calculi. The authors from New York describe their use of an irrigation protocol in 91 patients who had either an augmentation cystoplasty or continent urinary diversion. In addition to finding that patients with an abdominal stoma had a much higher chance of developing reservoir calculi, they found that using a definitive postoperative irrigation programme considerably reduced the incidence of calculi.

Bacillus Calmete-Guérin plus interferon-α2B intravesical therapy maintains an extended treatment plan for superficial bladder cancer with minimal toxicity

Bacillus Calmette-Guérin (BCG) and interferon-alpha2B (IFN-alpha2B) have both been individually used for the intravesical treatment of superficial bladder cancer. We report our experience on the therapeutic efficacy and toxicity of combined intravesical BCG plus IFN-alpha2B for treating superficial bladder cancer, including patients failing previous BCG therapy. Thirty-two patients with superficial bladder cancer underwent 6 weekly treatments with full-, one-third, or one-tenth-dose of BCG plus 50 or 100 MU of IFN-alpha2B based on prior BCG exposure and tolerance. Patients with no evidence of disease proceeded onto maintenance therapy of 3 weekly treatments at 3 months followed by 2 additional maintenance cycles given 6 months apart. Response was assessed by cystoscopy/biopsy every 3 months after treatment. Before BCG plus IFN-alpha2B treatment, 20 patients (63%) had previously failed intravesical BCG therapy, 27 (84%) had aggressive disease (stage T1, grade 3, or carcinoma in situ), 27 (84%) had recurrent disease, 14 (44%) had multifocal disease, and 6 (19%) had disease of over 4 years duration. At median follow-up of 22 months, 21 patients (66%) remain disease-free and 11 patients (34%) had disease-recurrence. Nineteen of 32 patients (59%) were disease-free after the initial induction cycle. Six of 11 patients 55% ultimately failing combination therapy did so at the first 3 to 4 month evaluation. Four of 7 patients (57%) benefited from salvage re-induction therapy. Of the 20 patients previously treated with BCG, 12 patients (60%) remain disease-free. Combination BCG plus IFN-alpha2B intravesical therapy was well tolerated. Combination intravesical BCG plus IFN-alpha2B is an effective and tolerable alternative for patients with superficial bladder cancer, including those patients in whom intravesical BCG therapy had previously failed. Benefits of this combination therapy may include potentially less morbidity, improved clinical efficacy, and in the long term, fewer patients undergoing radical therapy. However, radical treatment options should be pursued for early failures of this combination regimen in those patients with risk factors for recurrence and progression.

Ureteroscopic management of upper tract transitional cell carcinoma

The expanding experience with endoscopic techniques for treating upper tract urothelial malignancy demonstrates its safety and efficacy in carefully selected patients. Diagnostic accuracy can be enhanced, and pathologic confirmation of tumor grade and stage is possible. In carefully selected patients who have low-grade and low-stage disease, the results of endourologic management have been encouraging. Patients with an anatomic or functionally solitary kidney, bilateral disease, or significant renal insufficiency can often be considered candidates for endoscopic treatment as the first line of therapy. In the setting of low-grade, low-stage disease in a patient with a normal contralateral kidney, the role of endourologic management remains controversial. Adjuvant topical therapy with mitomycin C or BCG seems to be safe and well tolerated after endoscopic management of upper tract TCC.

Importance of surgical margins in the management of renal cell carcinoma.

Surgical resection remains the standard treatment for clinically localized renal cell carcinoma. Pathological features of the surgical specimen, including the margin status, play an important part in determining the patients prognosis. Negative surgical margins have traditionally been sought to maximize the efficacy of treatment. Initial concerns that partial nephrectomy might have high local recurrence rates compared with radical nephrectomy have now been minimized as a result of technological advances and refinements in surgical technique. Current concerns in relation to partial nephrectomy include the width of parenchymal tissue that should be removed to avoid positive surgical margins, effects of positive margins on recurrence-free survival, and the use of frozen-section analysis to determine margin status. Size of the surgical margin in partial nephrectomy does not seem to affect the risk of local tumor recurrence, and not all positive surgical margins lead to recurrent disease. Intraoperative frozen-section analysis is not definitive and its value in guiding the surgical management of renal tumors remains to be defined. Laparoscopic partial nephrectomy is emerging as an attractive approach for selected renal masses. Intraoperative use of ultrasound, cold-scissor parenchymal transection, embolization, and hilar clamping to achieve a bloodless operative field with clear visibility, may minimize the risk of positive margins during partial nephrectomy.