Matched pairs of human prostate stromal cells display differential tropic effects on LNCaP prostate cancer cells

Prostate stromal cells may play binary roles in the process of prostate cancer development. As the first to be encountered by infiltrating prostate cancer cells, prostate stromal cells form the first defense line against prostate cancer progression and metastasis. However, interaction between prostate cancer and stromal cells may facilitate the formation of a tumor microenvironment favoring cancer cell growth and survival. To establish an experimental system for studying the interaction between cancer and stromal cells, we isolated three matched pairs of normal and cancer-associated human prostate stromal clones. In this report, we describe the morphologic and behavioral characteristics of these cells and their effect on LNCaP prostate cancer cells in co-culture. Unlike LNCaP prostate cancer cells, the isolated prostate stromal clones are large fibroblast-like cells with a slow proliferation rate. Growth and survival of these clones are not affected by androgens. The stromal cells display high resistance to serum starvation, while cancer-associated stromal clones have differentiated survival ability. In co-culture experiments, the stromal cells protected some LNCaP prostate cancer cells from death by serum starvation, and cancer-associated stromal clones showed more protection. This work thus established a panel of valuable human prostate stromal cell lines, which could be used in co-culture to study the interaction between prostate cancer and prostate stromal cells

Assessing the minimum number of lymph nodes needed at radical cystectomy in patients with bladder cancer

To identify the likelihood of finding one or more positive lymph nodes (LNs) according to the number of LNs removed at radical cystectomy (RC), as the number of LNs removed affects disease progression and survival after RC. Between 1984 and 2003, 731 assessable patients had RC and bilateral pelvic lymphadenectomy at three different institutions. ROC curve coordinates were used to determine the probability of identifying one or more positive LNs according to the total number of removed LNs. Of the 731 patients, 174 (23.8%) had LNs metastases. The mean (median, range) number of LNs removed was 18.7 (17, 1-80). The ROC coordinate-based plots of the number of removed LNs and the probability of finding one or more LNs metastases indicated that removing 45 LNs yielded a 90% probability. Conversely, removing either 15 or 25 LNs indicated, respectively, 50% and 75% probability of detecting one or more LNs metastases. These data indicate that removing 25 LNs might represent the lowest threshold for the extent of lymphadenectomy at RC. Our findings confirm the importance of an extended lymph node dissection

Adjuvant chemotherapy for bladder cancer does not alter cancer-specific survival after cystectomy in a matched case-control study

OBJECTIVE To assess the effect of adjuvant chemotherapy (ACHT; methotrexate, vinblastine, adriamycin and cisplatin, MVAC, or gemcitabine/cisplatin, GC) on the rate of cancer-specific survival and overall survival, as the benefit of ACHT after radical cystectomy (RC) for bladder cancer is controversial. PATIENTS AND METHODS Within a study group of 958 patients treated with RC between 1984 and 2003, we identified 274 (29.0%) with a high risk of progression due to pT3 or pT4 and/or pN1-3 stages. Of these, 129 (46.6%) received ACHT (MVAC in 103, GC in 26). These patients were then matched with the remaining patients who were unexposed to ACHT. Exact matches were made for pT stage, tumour grade, pN stage and lymphovascular invasion. Age (+/- 5 years) and year of surgery (+/- 5 years) were calliper-matched. Matching resulted in 62 patients treated with RC/ACHT and 65 treated with RC alone. Kaplan-Meier, life-table and Cox regression analyses were used to assess cancer-specific and overall survival. RESULTS There was no statistically significant difference in cancer-specific survival probabilities at 5 years after RC between the two groups (relative risk 1.2; P = 0.5). There was also no difference in overall survival at 5 years (1.1; P = 0.7). In multivariable analyses the delivery of adjuvant chemotherapy was not an independent predictor for survival endpoints (P = 0.3 for cancer-specific and 0.3 for overall survival). CONCLUSIONS This matched case-control analysis showed that either MVAC or GC chemotherapy had no effect on cancer-specific or overall survival after RC in high-risk patients. Further randomized long-term studies are necessary to confirm these results

Validation of the AJCC TNM Substaging of pT2 Bladder Cancer: Deep Muscle Invasion Is Associated with Significantly Worse Outcome.

The current TNM bladder cancer staging system stratifies bladder muscle invasion into superficial (pT2a) and deep (pT2b). Controversy exists regarding the significance of the extent of muscle invasion on clinical outcome. OBJECTIVE: Our aim was to compare the cancer-specific outcomes of patients with pT2 urothelial carcinoma of the bladder (UCB) at radical cystectomy (RC) in a large international cohort of patients. DESIGN, SETTING, AND PARTICIPANTS: The records of patients treated with RC for UCB at six centers were reviewed. Of the 2605 reviewed patients, 565 (21.7%) had pT2 disease. None of the patients received preoperative systemic chemotherapy or radiotherapy. MEASUREMENTS: Patients' characteristics and outcome were evaluated. RESULTS AND LIMITATIONS: The median patient age in the entire group was 66.2 yr. Of the 565 patients with pT2 UCB, 249 patients (44.1%) had substage pT2a; 316 patients (55.9%) had pT2b. One hundred and eleven patients (19.6%) had metastases to regional lymph nodes. Median follow-up was 50.5 mo. Recurrence-free survival (73.2% vs 58.7%) and cancer-specific survival (78.0% vs 65.1%) estimates were significantly better for pT2a patients compared with those with pT2b (p=0.002 and p=0.001, respectively). Pathologic T2 substaging was associated with worse recurrence-free and cancer-specific survival after adjusting for the effects of standard pathologic features (p=0.011 and p=0.006, respectively). The statistical significance of these associations was reconfirmed in subgroup analysis limited to those patients with pathologically negative lymph nodes. CONCLUSIONS: In this large international cohort, pathologic substaging helped to stratify patients with lymph node-negative pT2 UCB into statistically significantly different risk groups. These data support the value of the current American Joint Committee on Cancer TNM staging