Osamu Maeda

Prospective Evaluation of Selection Criteria for Active Surveillance in Japanese Patients with Stage T1cN0M0 Prostate Cancer

OBJECTIVEnSelection criteria for active surveillance (AS) program of localized prostate cancer remain to be standardized. The purpose was to evaluate the validity of selection criteria and investigate the feasibility of this AS program.nnnMETHODSnPatients meeting the criteria (i) stage T1cN0M0, (ii) age 50-80, (iii) serum prostate-specific antigen (PSA) </=20 ng/ml, (iv) one or two positive cores per 6-12 systematic biopsy cores, (v) Gleason score </=6, and (vi) cancer involvement in positive core </=50% were enrolled and encouraged to start AS for at least 6 months during the period between January 2002 and December 2003. PSA was measured bimonthly for 6 months and every 3 months thereafter. Trigger of treatment recommendation was PSA-doubling time (PSADT) of </=2 years or pathological progression at re-biopsy. Primary endpoint was %PSADT > 2y, which was defined as the proportion of patients who showed PSADT assessed at 6 months >2 years out of all the patients who chose AS. Point estimate of %PSADT > 2y was expected to be >80%.nnnRESULTSnOne hundred and eighteen patients opted for AS and 16 chose immediate treatment at enrollment. PSADT for the initial 6 months based on four measurements could be assessed in 106 patients. Intent-to-treat analysis of %PSADT > 2y was 71.2% (84/118, 95% CI: 62.1-79.2). Pathological progression rate at 1-year re-biopsy was 33%. Fifty-four (46%) patients remained on AS for maximal observation of 54 months. General health-related QOL in patients undergoing AS was not impaired.nnnCONCLUSIONSnThe primary endpoint, %PSADT > 2y, did not meet the pre-specified decision criteria. Further prospective study with revised program and endpoint is needed.

Correlation of Initial PSA Level and Biopsy Features with PSA-Doubling Time in Early Stage Prostate Cancers in Japanese Men

OBJECTIVEnTo distinguish good candidates for watchful waiting from those who need immediate treatment in localized prostate cancer.nnnMETHODSnProstate specific antigen (PSA)-doubling time (DT) was calculated by a log-linear regression model for 78 patients with clinically localized prostate cancer (T1c: 47, T2a: 6, T2b: 21, and T3: 4) under surveillance. Median observation period was 37.5 months. The first 1-year PSA-DT was compared with the overall PSA-DT in 41 patients who had been under surveillance for more than 3 years.nnnRESULTSnThere was significant difference in the PSA-DT distribution between a pooled group of T1c and T2a and a group of T2b and T3 patients (median 58.8 versus 33.3 months, P = 0.0052). A combination of three parameters consisting of initial PSA level less than 10 ng/ml, WHO grade 1, one or two positive core per six to eight systematic biopsy cores with 50% or less cancer involvement significantly correlated with PSA-DT distribution in the T1c plus T2a group (P = 0.0034). The first year assessment of PSA-DT was identical to the overall assessment in 48.8%, 2 years or more in 36.6%, while it was 2 years or less (possibly over-estimated) in 14.6%.nnnCONCLUSIONnPSA-DT can be predictable to some extent with the initial PSA level and biopsy features in early stage prostate cancers. Prospective study is needed to clarify whether temporary observation together with PSA-DT estimation is a safe strategy and is complementary to clinico-pathological parameters at diagnosis.

Antitumor effect of CPT-11, a camptothecin derivative, on human testicular tumor xenografts in nude mice

OBJECTIVEnThe antitumor effect of CPT-11, a camptothecin derivative, on two human testicular embryonal carcinomas (TTSC-2 and TTSC-3) heterotransplanted into-nude mice was studied.nnnMATERIALS AND METHODSnTumor-bearing nude mice were given daily intraperitoneal injections of the anticancer drugs in 0.1 ml saline 3 times at 3-day intervals. At the end of the experiments tumors were resected and subjected to light-microscopic observation.nnnRESULTSnWhen 10, 30 and 50 mg/kg of CPT-11 was administered to tumor-bearing mice intraperitoneally, the antitumor effect of CPT-11 was observed dose-dependently in both TTSC-2 and TTSC-3. When 30 mg/kg of CPT-11 was administered in combination with CDDP, complete tumor regression was observed in both TTSC-2 and TTSC-3 tumors. Histological findings correlated well with the decrease in tumor volume of treated tumors. No mice died after treatment with CPT-11 in a single-agent and combination chemotherapy.nnnCONCLUSIONnChemotherapy with CPT-11 was an effective and safe method against human testicular tumors heterotransplanted in nude mice.

Solitary Neurofibroma of Scrotum

We report a case of solitary neurofibroma of the scrotum. These tumors, which arise from perineural and Schwann cells, commonly occur throughout the body but they rarely have been reported to originate in the scrotum. No stigmata of von Recklinghausens disease were identified.

Clinical Significance of Nonpalpable Prostate Cancer with Favorable Biopsy Features in Japanese Men

Objective: To assess the clinical significance of nonpalpable localized prostate cancers with relatively favorable six sextant biopsy features in Japanese men.Patients and Methods: 136 nonpalpable prostate cancers of which biopsy features confined to (1) a Gleason score of 6 or less, (2) one or two positive cores per six sextant cores, and (3) 50% or less involvement of any positive core were collected. The Gleason score, tumor extension, and cancer volume were compared with preoperative serum PSA and PSA density for the patients who underwent radical prostatectomy. PSA doubling time was measured for the patients who were treated expectantly.Results: Treatments chosen for 136 patients with favorable biopsy features were radical prostatectomy alone for 48 and with preoperative androgen deprivation for 30, radiation to the prostate for 12, androgen deprivation therapy for 21, and watchful waiting for 25. Of 48 patients who underwent radical prostatectomy without androgen deprivation therapy, 25% had nonorgan–confined cancers. Seven cancers (14.6%) were Gleason score of 7, but no cancers were 8 or greater. Among 42 prostatectomy specimens for which cancer volume was measured, 22 (52.4%) had cancer volume >0.5 cm3. Pretreatment serum PSA levels were correlated neither with the Gleason score, tumor extension nor cancer volume. There was only one nonorgan–confined cancer in the 23 cancers for which PSA density was <0.2 ng/ml/g. The ability of PSA density to predict cancer volume <0.5 cm3 was 0.61 using a cut–off of 0.2 ng/ml/g. Of the 25 patients treated expectantly, the PSA doubling time was less than 2 years for 3 patients, while it was stable or fluctuated for 13.Conclusions: Tumor extension can be predicted based on PSA density in nonpalpable prostate cancer with favorable biopsy features, but predictability of cancer volume based on PSA or PSA density is not satisfactorily high. New parameters or biomarkers that complement needle biopsy findings are needed to predict clinical significance of T1c prostate cancer with favorable biopsy features.

45X/46XX Boy with Hypospadias: Case Report

A 21-month-old boy with penoscrotal hypospadias had chromosomal mosaicism of 45X/46XX karyotype, which was confirmed by examination of cultured peripheral lymphocytes and fibroblasts from the genital skin. The H-Y antigen from the peripheral blood was positive. This case represents an example of 45X/46XX mosaicism presenting as an almost normal male phenotype with a scrotal testis.