Bone scan index can be a useful biomarker of survival outcomes in patients with metastatic castration-resistant prostate cancer treated with radium-223.

BACKGROUND: Bone metastasis of prostate cancer is associated with pain and reduced overall survival (OS). Radium-223, which is expected to reduce bone pain and prolong OS, was recently approved in Japan. AIM: The aim of this study was to investigate the usefulness of the bone scan index by comparing the outcomes and factors according to response in Japanese patients treated with radium-223. METHODS AND RESULTS: Twenty patients receiving radium-223 were divided into two groups according to whether they did or did not achieve a bone scan index decrease of at least one point (beneficial and non-beneficial groups, respectively). The clinical characteristics at baseline and after three and six treatment cycles were compared using χ2 tests and Student's t-tests or Mann-Whitney U tests, and survival was estimated and compared using the Kaplan-Meier method and log-rank test, respectively. Fourteen (70%) and six patients (30%) were categorized into the beneficial and non-beneficial groups, respectively. Patients in the former group were significantly more likely to have a higher Eastern Cooperative Oncology Group performance status score and receive a greater number of radium-223 injections (P < 0.05). Furthermore, patients in the beneficial group had a significantly longer OS (P < 0.05). Regarding safety, one and three patients in the beneficial and non-beneficial groups, respectively, prematurely discontinued radium-223 because of an increased prostate-specific antigen level, decreased hemoglobin level, or femoral fracture. CONCLUSION: Radium-223 appears generally safe in this population. Patients with good bone scan index response have better performance status, receive more injections of radium-223, and achieve OS prolongation. Bone scan index is a useful biomarker of survival outcomes and can be a valuable assessment tool in patients with metastatic castration-resistant prostate cancer who are treated with radium-223.

Lymphovascular invasion predicts poor prognosis in high-grade pT1 bladder cancer patients who underwent transurethral resection in one piece.

BACKGROUND: Lymphovascular invasion (LVI) in high-grade clinical T1 bladder cancer is usually considered a poor prognostic factor, but it is often difficult to achieve correct staging of T1 bladder cancer and diagnose the presence of LVI because of the inadequacy of conventional transurethral resection specimens. The aims of this study were to evaluate the prognostic value of LVI in patients with correctly staged high-grade pathological T1 (pT1) bladder cancer who initially underwent transurethral resection in one piece (TURBO). METHODS: Eighty-six high-grade pT1 bladder cancer patients who underwent TURBO were enrolled. Risk of tumor understaging was avoided by examining the vertical resection margin of the TURBO specimen. Immunohistochemical staining using D2-40 and CD31 was performed to confirm LVI. We examined the association of LVI with other clinicopathological factors and the impact of LVI on progression-free survival and cancer-specific survival. RESULTS: The median follow-up period was 49 months (range, 6-142). In all patients, the tumors were accurately staged as pT1 at initial TURBO. LVI was detected in 15 patients (17%) and was significantly associated with tumor growth pattern (P = 0.001). Multivariate analysis identified LVI as the only independent predictor for reduced progression-free survival (HR, 4.48; 95% CI, 1.45-13.90; P = 0.009) and cancer-specific survival (HR, 4.35; 95% CI, 1.17-16.24; P = 0.029). CONCLUSIONS: The presence of LVI in TURBO specimens independently predicts poor clinical outcomes in patients with high-grade pT1 bladder cancer. This information may help urologists to counsel their patients when deciding whether to choose a bladder-preserving strategy or radical cystectomy.

Transurethral resection in one piece (TURBO) is an accurate tool for pathological staging of bladder tumor.

OBJECTIVES: To demonstrate the usefulness of transurethral resection in one piece (TURBO) as an accurate pathological staging tool for bladder tumor. METHODS: Ninety-seven patients with newly diagnosed bladder cancer underwent TURBO that was performed either in an en bloc or in a divisional manner. The histological quality of the resection specimens was evaluated and the pathological stage was assigned on the basis of the depth of invasion, which was histologically determined. RESULTS: Specimens obtained by TURBO were well oriented and their 3-D architecture was maintained. This allowed a histological assessment of the entire specimen. Portions of muscularis propria were identified beneath the tumor base in the specimens of 80 (82%) patients. In only seven (7%) patients, the tumors had a deep resection margin positive for carcinoma and were ambiguously staged as "pT1 or higher" or "pT2 or higher". Thus, definite pathological staging of TURBO specimens was possible in 90 (93%) patients (pTa, 30; pT1, 58; pT2, 2). CONCLUSIONS: An accurate pathological stage can be assigned to the TURBO specimen in most bladder cancer patients.

Amphoterin induction in prostatic stromal cells by androgen deprivation is associated with metastatic prostate cancer.

Amphoterin, the major product of the high mobility group-1 gene, is a ligand associated with cancer invasion and metastasis through activation of the receptor for advanced glycation end products (RAGE). Expression of amphoterin and RAGE was examined in prostatectomy specimens from 40 patients with pT3 prostate cancer (18 non-metastatic and 22 metastatic) preoperatively treated with lutenizing hormone-releasing hormone (LH-RH) agonist. Amphoterin expression was detected in tumor cells of 6 (27%) metastatic and 0 non-metastatic cases (p<0.0001). Amphoterin was also detected in prostatic stromal cells of 14 (63%) metastatic cases and 2 (11%) non-metastatic cases (p=0.0010). RAGE production was detected in cancer cells of 16 (73%) metastatic and 6 (33%) non-metastatic cases (p=0.0244). A total of 2 (22%) non-metastatic and 16 (73%) metastatic cases showed co-expression of amphoterin and RAGE in tumor cells or in tumor cells and stromal cells (p=0.0001). The in vitro invasive capacity of PC-3, a prostatic cancer cell line that co-expressed amphoterin and RAGE, was suppressed by treatment with amphoterin antisense S-oligodeoxynucleotide (ODN). Primary cultured human prostatic stromal cells secreted no amphoterin; however, amphoterin secretion was induced by androgen deprivation. The conditioned medium of human prostatic stromal cells deprived of androgen recovered the in vitro invasive capacity of PC-3 cells suppressed by amphoterin antisense S-ODN. These results suggest that androgen deprivation provides a paracrine interaction between cancer and stromal cells through the RAGE-amphoterin system in advanced prostate cancer.

The relative mRNA expression levels of matrix metalloproteinase to E-cadherin in prostate biopsy specimens distinguishes organ-confined from advanced prostate cancer at radical prostatectomy.

PURPOSE: To determine whether the expression ratio of matrix metalloproteinase (MMP) to E-cadherin mRNA (MMP:E-cadherin) in biopsy (BX) samples of prostate cancer correlate with that of radical prostatectomy (RP) specimens and assists in predicting pathologic stage. EXPERIMENTAL DESIGN: The mRNA expression levels for MMP-2 and -9 and of E-cadherin were determined by a colorimetric in situ hybridization assay in 44 paired BX and RP specimens. Clinical stage, BX Gleason score (GS), total length of cancer in BX cores, and serum prostate-specific antigen levels were also assessed. RESULTS: Clinical stage was confined in 39 of 44 (89%) patients. Subsequent to RP, however, only 17 of 44 (39%) patients had proven organ-confined disease (pT2). BX GSs agreed with the RP GS in 77% of RP specimens. We found a strong correlation between BX and RP MMP:E-cadherin ratios (correlation coefficient = 0.755). The ratio increased as the GS increased and pathologic stage advanced (pT2 versus >/= pT3). Increasing clinical stage, GS, and serum prostate-specific antigen were significantly associated with advanced cancer at RP (P = 0.004-0.0001). The BX MMP:E-cadherin ratio, however, exhibited the strongest association with pathologic stage and independently predicted the status of 89% of the RP cases based on a BX ratio of <6 (predicted stage pT2 cancer at RP) versus >/=6 (predicted stage >/= pT3 at RP). CONCLUSION: The BX MMP:E-cadherin ratio represents a novel prognostic assay for predicting stage of cancer at RP. These data provide proof of principle for directly assessing the biological potential of prostate cancer using molecular strategies in patient's specimens.