Predictors of poor response to first-generation anti-androgens as criteria for alternate treatments for patients with non-metastatic castration-resistant prostate cancer.

PURPOSE: There are no criteria for administering first- or second-generation anti-androgens (FGA and SGA, respectively) to patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This study aimed to assess the efficacy of alternative FGA therapy in nmCRPC patients and the prognosis of these patients and to identify factors for predicting patients potentially responsive to FGA. METHODS: Data from 63 men with nmCRPC who underwent alternative FGA therapy (bicalutamide, flutamide, or chlormadinone acetate) as first-line therapy after failure of primary androgen-deprivation therapy (PADT) between 2004 and 2017 at Hiroshima University Hospital and affiliated hospitals were retrospectively investigated. The associations of clinicopathological parameters with overall survival (OS) and prostate-specific antigen (PSA) progression-free survival (PFS) of alternative FGA-treated patients were analyzed. RESULTS: Time to CRPC [p = 0.007, hazard ratio (HR) = 4.77], regional lymph node involvement at the diagnosis of CRPC (p = 0.022, HR = 2.42), and PSA-PFS of alternative FGA therapy ≤ 6 months (p = 0.020, HR = 2.39) were identified as prognostic factors using a multivariate analysis. Additionally, Cox proportional hazard models revealed that PSA nadir value > 1 ng/mL during PADT (p = 0.034, HR = 2.40) and time from starting PADT to PSA nadir ≤ 1 year (p = 0.047, HR = 1.85) were predictive factors for worse PSA-PFS in alternative FGA therapy. CONCLUSIONS: Shorter time to CRPC, regional lymph node involvement, PSA nadir during PADT > 1 ng/mL, and time from starting PADT to PSA nadir ≤ 1 year might suggest the potential benefit of immediate commencement of SGA, compared to FGA administration after nmCRPC diagnosis.

The short term feasibility of abdominoperineal resection with prostatectomy for locally advanced rectal cancer: open and laparoscopic cases report.

Total pelvic exenteration is often selected for advanced rectal cancer with prostatic invasion. The aim of this study was to evaluate the short term feasibility of the abdominoperineal resection with prostatectomy for locally advanced rectal cancer. We performed abdominoperineal resection with prostatectomy for 3 patients with locally advanced rectal cancer, including 2 patients by totally laparoscopic procedure. Patients' background, intra- and postoperative factors and short-term prognosis were evaluated. All patients underwent complete resection of primary tumor with negative surgical margins. We could perform the surgery by both open and laparoscopic procedure in collaboration with urologist. There was no operation related mortality. One patient who was treated by open procedure had urinary anastomotic leakage. No patient had recurrenced, but one patient died of other disease. Our experience suggests that open or laparoscopic abdominoperineal resection with prostatectomy could be an alternative to total pelvic exenteration for the patients with rectal cancer invading the prostate. The collaboration with the urologist would be important to perform quality-controlled surgery.

Possibility of using mRNA expression levels for nucleic acid-metabolizing enzymes within prostate cancer cells as indices for prognostic factors.

Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) are enzymes involved in nucleic acid metabolism. It has been reported (based on observations of various tumor types) that the extent of the mRNA expression of these enzymes within tumor tissues may be used as a factor to define tumor prognosis. It has also been reported that the mRNA expression patterns differ in each type of tumor. However, few reports are available on the distribution of mRNA expression in prostate cancers. This study was conducted on tissue specimens obtained from 172 patients who were diagnosed with prostate cancer and had undergone total prostatectomies. The mRNA expression of TS, DPD, OPRT and TP was quantitatively analyzed using the Danenberg tumor profile (DTP) method. The results were used to examine the correlations between the distributions of the mRNAs and clinicopathological factors, as well as the significance of their expression as a prognostic factor. Patients with poorly differentiated cancers in their tissues showed a significant increase in the mRNA expression of TS and OPRT. The increases in the TP mRNA content were proportional to an increase in the Gleason scores. The prognosis was significantly poorer in those cases with a high expression of TS or OPRT mRNA and a low expression of DPD mRNA. In conclusion, the expression levels of mRNAs for TS, DPD and OPRT among the enzymes related to nucleic acid metabolism are useful as prognostic factors in patients with prostate cancers.

[Neuroendocrine carcinoma of the prostate effectively treated by cisplatin and irinotecan--a case report].

A 79-year-old man was referred to our hospital with urinary retention in August 2004. Because the serum PSA was 2,9 39 ng/mL,we performed transabdominal prostatic needle biopsy. Pathological examination of the prostate revealed conventional adenocarcinoma. CT scans and MRI showed a huge mass and lymph node metastasis. He was treated with diethyl stilbestrol diphosphate,followed by maximal androgen blockade therapy,and the serum PSA level decreased favorably. Follow-up CT revealed prostate and lymph node metastasis were reduced, but liver metastases, measuring 45 x 34 mm and 28 x 24 mm, respectively, were newly recognized in February 2006. The NSE level was high at 88.5 ng/mL, so a percutaneous liver biopsy was performed,and pathological examination of the liver revealed metastatic prostate cancer which showed neuroendocrine differentiation. The treatment was changed to chemotherapy comprising cisplatin and irinotecan. After three courses of the chemotherapy,liver metastasis was reduced in CT scans.