Dan Theodorescu

Note: In lieu of an abstract, this is an excerpt from the first page. Cells are complex systems that regulate a multitude of biologic pathways involving a diverse array of molecules.

Metastasis remains the major driver of mortality in patients with cancer. The similarities and differences between primary tumors and metastases are described, and pathways controlling the colonization of a distant organ and incorporation of anti-metastatic therapies into clinical testing are discussed. The authors emphasize that the time is ripe for metastasis and metastatic colonization to enter mainstream clinical development and testing. Metastasis remains the major driver of mortality in patients with cancer. Our growing body of knowledge regarding this process provides the basis for the development of molecularly targeted therapeutics aimed at the tumor cell or its interaction with the host microenvironment. Here we discuss the similarity and differences between primary tumors and metastases, pathways controlling the colonization of a distant organ, and incorporation of antimetastatic therapies into clinical testing.

Associate Editor Ash Tewari Editorial Board Ralph Clayman, USA Inderbir Gill, USA Roger Kirby, UK Mani Menon, USA OBJECTIVE: To compare the performance of radical cystectomy with ileal conduit diversion by standard methods with that using the assistance of the daVinci robotic system (Intuitive Surgical, Sunnyvale, CA, USA). PATIENTS AND METHODS: From November 2003 to August 2005, we performed 30 radical cystectomies with ileal conduit urinary diversions on patients with bladder cancer. Seven patients (one woman) had a cystectomy with the daVinci system and 23 (nine women) had a standard cystectomy. Data were collected prospectively, including estimated blood loss (EBL), transfusion requirement, operative duration, hospital stay and body mass index (BMI), and compared. RESULTS: The mean EBL and transfusion requirements for standard and daVinci‐assisted cases was 1109 and 479 mL ( P = 0.002) and 2.7 and 1.6 units ( P = 0.14), respectively. Four of seven patients received a transfusion in the robotic group, and 20 of 23 in the standard group ( P = 0.084). The mean operative duration was 638 and 507 min ( P = 0.005) for the daVinci and standard group, respectively, with respective mean hospital stays of 11 and 13 days ( P = 0.52). There was no difference in patient BMI between the groups ( P = 0.22). CONCLUSION: The daVinci‐assisted cystectomy appears to offer some advantages over standard cystectomy. Larger randomized studies are needed to confirm these findings.

Minimally invasive approaches have been shown to offer considerable benefits to patients in the treatment of urologic malignancies. While open radical cystectomy remains the gold standard for the treatment of muscle invasive bladder cancer, the continued refinement of laparoscopic techniques and the success of robotic assistance in radical prostatectomy have led to great interest in minimally invasive approaches to radical cystectomy. We review the current experience with laparoscopic and robotic radical cystectomy and its role in the treatment of muscle invasive bladder cancer.

We describe the use of capillary eletrophoresis (CE) coupled with mass spectrometry (MS) to identify single polypeptides and patterns of polypeptides specific for prostate cancer (CaP) in human urine. Using improved sample preparation methods that enable enhanced comparability between different samples, we examined samples from 47 patients who underwent prostate biopsy. Of this group, 21 patients had benign pathology and 26 with CaP, and these were used to define potential biomarkers, which allow discrimination between these two states. In addition, CE‐MS data from these 47 urine samples were compared to that of 41 young men (control) without known or suspected clinical CaP to further confirm the polypeptides indicative for CaP. Upon crossvalidation of the same samples, several polypeptides were selected that enabled correct classification of the CaP patients with 92% sensitivity and 96% specificity. We then examined an additional 474 samples from patients with renal disease enrolled in other studies and found that 14 (3%) had polypeptides suggestive of CaP possibly indicating that they harbor clinical CaP. In conclusion, this early pilot study suggests that CE‐MS of urine warrants further investigation as a tool that can identify putative biomarkers for CaP.

BACKGROUND The concept of a prostate-specific antigen (PSA) “nadir” has been used as a predictive marker for treatment success in patients treated with radiotherapy for localized prostate carcinoma. However, this approach is not applicable in patients who are concomitantly treated with short-term hormonal therapies. To address this, the authors sought to develop a new predictive marker in such patients after prostate brachytherapy (BT). METHODS Between March 1997 and November 2002, 194 men with clinical Stage T1A-T3N0M0 prostate carcinoma (according to the 1992 International Union Against Cancer/American Joint Committee on Cancer TNM classification system) were treated with interstitial palladium (¹⁰³Pd 3 ) BT and androgen ablation therapy with or without external beam radiotherapy (EBRT). Based on tumor characteristics, 127 patients received an antiandrogen, finasteride, and BT whereas 67 received an antiandrogen, leuprolide, and EBRT followed by a BT boost. Hormonal therapy was initiated 2–3 months before any radiotherapy for a total duration of 8–9 months. Follow-up included physical examination and determining the PSA level at 3-month intervals. Postoperative serum testosterone was evaluated in preoperatively potent patients with erectile dysfunction > 6 months after therapy. A PSA level ≤ 0.06 ng/mL or ≤ 0.20 ng/mL detected during a 6–12-month window after the implant were evaluated as predictors of biochemically disease-free survival (DFS), defined as the time to a PSA level ≥ 1.0 ng/mL. RESULTS Of the 194 patients, 163 were available for analysis. The median length of follow-up was 48 months. In those patients with a PSA level ≤ 0.20 ng/mL at 6–12 months, the DFS at 48 months after the implant was 96% (95% confidence interval [95% CI], 91–99%) compared with the remainder of the patients, whose DFS decreased to 80% (95% CI, 65–89%) (P < 0.001). When a PSA level ≤ 0.06 ng/mL was used as an indicator, the 48-month DFS was 99% (95% CI, 91–100%) compared with that for patients with a PSA level > 0.06 ng/mL, in whom the DFS was 85% (95% CI, 74–92%) (P = 0.004). Furthermore, because testosterone levels may occasionally remain low after the cessation of luteinizing hormone-releasing hormone agonist therapy and result in erectile dysfunction and an artificially low PSA level, the authors reviewed the serum testosterone levels in 23 patients who were so treated and were experiencing erectile dysfunction. None had PSA values below the lower limit of normal. CONCLUSIONS A PSA level ≤ 0.20 ng/mL or ≤ 0.06 ng/mL measured at 6–12 months after BT appears to be a useful predictive marker for detecting early success in patients with prostate carcinoma who are treated with neoadjuvant androgen ablation and BT. These markers may be used to identify those patients who are at an increased risk of biochemical failure and may be useful in stratifying patients for closer follow-up, long-term adjuvant therapies, or clinical trials. A longer follow-up period will be needed to verify whether these are predictive of long-term cancer control. Cancer 2005. © 2005 American Cancer Society.

OBJECTIVE: To assess the long‐term quality of life (QoL) outcomes of three treatments for localized prostate cancer: radical prostatectomy (RP); brachytherapy monotherapy (BTM); and BT combined with external beam radiotherapy (BTC). PATIENTS AND METHODS: In August 2000, questionnaires were mailed to men with T1c‐T3 adenocarcinoma of the prostate treated with either RP, BTM ( ¹⁰³ Pd monotherapy) or BTC. Questionnaires included validated outcome measures, i.e. the Functional Assessment of Cancer Therapy − General (FACT‐G), American Urological Association Symptom Score (AUA‐SS), Urinary Function Questionnaire for men after RP, and the Brief Sexual Function Inventory. Returned questionnaires were assessed using cross‐sectional analysis. RESULTS: Data from 214 patients were included in the analysis (60 RP, 102 BTM and 52 BTC); the median follow‐up was 18.8, 25.5 and 29.9 months, respectively. There were differences between both BT groups and the RP group in total AUA‐SS and obstructive subscale symptom scores, with the former having worse symptom scores at a longer follow‐up. Differences in overall QoL were not detected between groups using the total FACT‐G but the BTC group generally had worse scores in the physical well‐being subscale. The BT groups had higher continence rates with time after treatment. Sexual function was better with BT initially, but these differences did not persist at a longer follow‐up. There were significant correlations between the FACT‐G and the urinary symptom scores, and the degree of sexual function. CONCLUSIONS: Although patients treated with BTM and RP have a different spectrum of side‐effects, their overall long‐term QoL is similar, with urinary and sexual function being the primary determinants of this outcome. Men treated with BTC have a worse QoL.

Brachytherapy for prostate cancer has become a widely used treatment. Increasingly, urologists are becoming conscious of quality‐of‐life issues relating to treatment. This mini‐review by authors from the University of Virginia looks at this important issue, reminding readers that patients are often willing to choose a treatment which will less certainly ensure a longer life‐expectancy, but which will more certainly guarantee a better quality of life. Other mini‐reviews in this section describe the technique and complications of transurethral surgery for bladder tumours, the mechanisms of vasculogenic erectile dysfunction after renal transplantation, and laparoscopic radical cystectomy and urinary diversion.