Risk stratification of high-grade prostate cancer treated with antegrade radical prostatectomy with intended wide resection.

OBJECTIVE: The aim of this study was to assess the surgical outcome of high-grade prostate cancer (PCA) treated with antegrade radical prostatectomy with intended wide resection (aRP) and to establish the risk stratification. METHODS: A consecutive 77 Japanese patients with Gleason score 8-10 PCA were treated with aRP alone and excluding patients with persistently elevated prostate-specific antigen (PSA), prospectively observed without any treatment until PSA failure was confirmed. PSA failure-free, cancer-specific and overall survival curves were generated with Kaplan-Meier method and the difference between groups was assessed with log-rank test. Cox's proportional hazards model was used to elucidate predictors of PSA failure. RESULTS: During a median follow-up of 6 years, PSA failure was observed in 41 (53%) of the 77 patients. Five- and 10-year PSA failure-free survival rates of the entire cohort were 44.6% and 40.1%, respectively. Both overall and cancer-specific survival rates of the entire cohort at 5 and 10 years were 96.8% and 87.9%, respectively. In a multivariate analysis, PSA (P = 0.008), specimen confinement (SC) (P = 0.006) and persistently elevated PSA after aRP were identified as significant and independent predictors of PSA failure. When stratifying patients into three risk groups according to PSA level and SC status, PSA failure-free survival rate in patients with PSA < 10 ng/ml and specimen-confined disease (SCD) was significantly better than that in those of any other groups. CONCLUSIONS: Good prognosis can be expected in patients with high-grade PCA treated with aRP alone when PSA < 10 ng/ml and the tumor was removed as an SCD.

Prognostic significance of cancer volume involving seminal vesicles in patients with pT3bpN0 prostate cancer.

OBJECTIVES: To investigate the prognostic effect of the prostate cancer (PCa) volume involving the seminal vesicles (CVSVs) in the radical prostatectomy specimen from patients with Stage pT3bpN0 PCa. METHODS: We retrospectively reviewed the clinical records of 27 patients with Stage pT3bpN0 PCa who had undergone radical prostatectomy alone. We measured the CVSVs using a grid method on the glass slide under microscopic inspection and investigated the association of the CVSVs with clinicopathologic variables. RESULTS: Prostate-specific antigen (PSA) failure was confirmed in 11 of the 27 patients (41%) during a median follow-up of 34 months. The 3-year PSA failure-free survival rate was 48%. The median CVSVs was 1.14 cm(3). On univariate analysis, a CVSVs of >1.63 cm(3) was associated with positive surgical margins (P = .018), bilateral seminal vesicle involvement (P = .03), a long maximal tumor dimension (P = .031), and a greater preoperative PSA level (P = .0007). The 3-year PSA failure-free survival rate for those with a CVSVs of 1.63 cm(3) was 80% and 0%, respectively (P = .0009). On multivariate analysis, only the PSA level and CVSVs were identified as significant and independent predictors of PSA failure. Stratifying patients into 3 risk groups by these predictors, the PSA failure-free survival rate for patients with a PSA level >or=10 ng/mL and a CVSVs of >1.63 cm(3) was significantly worse than for any other group. CONCLUSIONS: The CVSVs is useful and invaluable as an independent predictor of PSA failure in patients with Stage pT3bpN0 PCa. The measurement of the CVSVs is simple and helped to determine the indication for adjuvant treatment after radical prostatectomy.

Lymphovascular invasion is an independent predictor of prostate-specific antigen failure after radical prostatectomy in patients with pT3aN0 prostate cancer.

OBJECTIVES: To investigate the association of lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens with prostate-specific antigen (PSA) failure in patients with pT3aN0 prostate cancer (PCA). METHODS: We retrospectively reviewed the clinical records of 94 patients with pT3aN0 PCA treated with RP alone. All of the 94 patients were prospectively observed without any treatment until PSA failure was confirmed. We investigated the association of LVI with the adverse pathological findings in RP specimens and the PSA failure-free survival rate. The Cox proportional hazard model was used to elucidate predictors of PSA failure. RESULTS: Median follow up was 47.4 months (quartile range 9.1 to 146.8). LVI was found in 26 (27.7%) of the 94 patients. In a multivariate analysis, PSA (P = 0.0054) and LVI (P = 0.015) were significant and independent predictors of PSA failure. Stratifying patients into four risk groups by LVI status and PSA level, the PSA failure-free survival rate in patients with negative LVI and PSA < or =10 ng/mL was significantly better than any other groups (positive LVI and/or PSA >10 ng/mL). CONCLUSIONS: Adjuvant therapy would not be indicated to patients with pT3aN0 PCA with negative LVI and PSA < or =10 ng/mL.

Successful 2-year-long remission following repeated salvage surgery in a patient with chemotherapy-resistant metastatic nonseminomatous germ cell tumor.

A 34 year-old man with a diagnosis of nonseminomatous testicular cancer with retroperitoneal lymph node metastasis (T1N3M0S2, stage IIIb; intermediate prognosis, made after right inguinal orchiectomy was performed) was referred to our hospital after having had a total of eight courses of systemic chemotherapy and external-beam radiotherapy to the retroperitoneal region in the previous 1 year. His serum alpha-fetoprotein (AFP) level remained elevated. Two courses of paclitaxel, etoposide, and cisplatin combined chemotherapy (TEP; paclitaxel 120 mg/m(2) day 1, etoposide 80 mg/m(2) days 2-5, cisplatin 20 mg/m(2) days 2-5) failed to normalize the AFP level. During the following 2 years he underwent salvage surgery four times; infrarenal retroperitoneal lymph node dissection (RPLND), left neck lymph node dissection, thoracic duct excision, and suprarenal RPLND. Viable cancer cells were found in all surgically resected specimens, except for the neck lymph node specimen. The serum AFP level was normalized and he has been well without relapse for 2 years after the last surgery. The present case suggests that repeated salvage surgery may be beneficial in selected patients with a chemotherapy-resistant metastatic germ cell tumor.

Preoperative serum testosterone level as an independent predictor of treatment failure following radical prostatectomy.

OBJECTIVES: Preoperative low serum testosterone (TS) level has been reported to be associated with adverse pathologic results in patients with clinically localized prostate cancer (pCA) treated with radical prostatectomy (RP). However, prior studies failed to show prognostic impact of preoperative low TS in these patients. The aim of this study was to investigate the relationship between preoperative TS and prostate-specific antigen (PSA) failure in these patients. METHODS: Of 304 patients diagnosed with clinically localized pCA who had been treated with RP alone, 272 patients whose preoperative TS level had been measured were eligible for this analysis. Postoperative TS levels were also available in 222 of the 272 patients. Cox proportional hazard model was used to elucidate factors predictive for PSA failure. RESULTS: Of the 272 patients 49 had low (< 300 ng/dl) and 223 had normal preoperative TS level. In a stepwise multivariate analysis, preoperative TS (p = 0.021) was an independent and significant predictor of PSA failure along with RP Gleason score (p = 0.006), surgical margin status (p = 0.0001), and PSA (p = 0.0001). Five-year PSA failure-free survival rate of the patients with preoperative low TS (67.8%) was significantly worse than that with normal TS (84.9%) (p=0.035). Serum TS levels increased significantly after RP (p < 0.0001). The increment of TS level in preoperative low TS group was significantly greater than that in preoperative normal TS group (p = 0.0003). CONCLUSIONS: The current results demonstrated that preoperative TS level is an independent and significant predictor of PSA failure after RP in patients with clinically localized pCA.

Possibility of recovery of estrogen sensitivity following high-dose glucocorticoid therapy in a patient with hormone-refractory prostate cancer.

A 74-year-old man underwent irradiation therapy (RT) to the prostate bed because of prostate-specific antigen (PSA) failure after retropubic radical prostatectomy (RRP). Six months after the RT, a solitary bone metastasis developed in the third thoracic vertebra, and hormonal therapy (HT) was initiated. Three years later, following the loss of response to all hormonal agents, including oral estrogen and glucocorticoid therapy, paraplegia developed, due to a spinal metastasis. RT and high-dose glucocorticoid therapy were given for the spinal metastasis. Diethylstilbestrol diphosphate (DES-DP) was given continuously during this treatment, except for a 1-month period when the patient had pneumonia. After the RT and high-dose glucocorticoid therapy, his serum PSA decreased, from 308 to 36.99 ng/ml. In accordance with the 1-month discontinuation, and then resumption of DES-DP, the serum PSA levels went up and down. So we suspected that the tumor had recovered sensitivity to DES-DP with the high-dose glucocorticoid therapy. With a further decrease of serum PSA to 2.12 ng/ml, he has been alive for more than 3 years to date since the diagnosis of hormone-refractory prostate cancer (HRPCA). To our knowledge, there have been no reports showing such a marked recovery of hormone-sensitivity in HRPCA. No optimal therapy has yet been established for HRPCA; therefore, high-dose glucocorticoid therapy in combination with DES-DP warrants further study.

Phase I/II study of a combined gemcitabine, etoposide, and cisplatin chemotherapy regimen for metastatic urothelial carcinoma.

BACKGROUND: The authors attempted to determine the maximum tolerated dose (MTD) of gemcitabine in combination with etoposide and cisplatin as a chemotherapy regimen and investigated the safety and antitumor activity with the recommended doses of gemcitabine with etoposide and cisplatin for patients with metastatic urothelial carcinoma. METHODS: Patients age 75 years or younger with measurable lesions, creatinine clearance>or=50 mL per minute, and adequate bone marrow and hepatic function were studied. Etoposide and cisplatin were given on Days 1 through 3 at fixed doses of 75 mg/m2 and 25 mg/m2, respectively, and gemcitabine was given on Days 1, 8, and 15. In the Phase I component, gemcitabine was administered at increasing doses from 600 mg/m2. Cycles were repeated every 28 days unless progressive disease was encountered. RESULTS: In Phase I, with the initially fixed doses of etoposide and cisplatin, the MTD of gemcitabine could not be determined because of the occurrence of dose-limiting toxicity at Level 1 in all 3 patients. When the doses of etoposide and cisplatin were modified to 60 mg/m2 and 20 mg/m2, respectively, the MTD of gemcitabine was 1000 mg/m2. Next, 19 additional patients were entered into Phase II with the recommended gemcitabine dose of 800 mg/m2, and 20 patients in all were treated at this dose level. The main toxicity was bone marrow suppression, with Grade 3 or 4 neutropenia and thrombocytopenia recognized in 20 patients (100%) and 14 patients (70%), respectively, although no toxic deaths occurred. In total, all 31 patients at all dose levels had an assessable response, with 6 complete responses and 15 partial responses observed, for an overall response rate of 67.7%. Patients who had visceral metastasis had a significantly worse response rate than patients who had lymph node metastasis alone (50.0% vs. 78.9%; P=.042). The response rate (66.7%) for 21 patients who received prior chemotherapy was not different from that for 10 chemotherapy-naive patients. The median survival for all patients was 13.1 months, and 4 patients survived for >2 years with no evidence of disease. Patients younger than age 65 years had significantly better survival than patients age 65 years or older (P=.026). CONCLUSIONS: Although bone marrow toxicity was considerable, combination chemotherapy with gemcitabine, etoposide, and cisplatin appeared to be very active in patients with urothelial carcinoma and may be especially promising for younger patients, although further study is warranted.

[The result of VIP chemotherapy as an induction therapy in 6 patients with non-seminomatous extragonadal germ cell tumor].

We treated 6 patients with non-seminomatous extragonadal germ cell tumor (NSEGCT) by VP-16 + ifosfamide + cisplatin (VIP) chemotherapy as an induction therapy to investigate the effectiveness and safety. Primary lesions were located at the mediastinum in 4 patients and the retroperitoneum in 2 patients. As a rule, all patients were treated with VIP chemotherapy of 4 courses with or without second-line treatment such as chemotherapy, residual tumor resection and/or radiation. Following the induction therapy (VIP), 4 of 6 patients (67%) achieved complete or partial responses. After salvage therapy, 4 patients (67%) achieved complete responses and two other patients also achieved partial responses. However, only 2 of the 5 patients who had been follow-up for more than 2 years have remained disease free. The effects of VIP chemotherapy on non-seminomatous extragonadal germ cell tumor appeared to be similar to those of the conventional chemotherapies though the number of patients was small in the current study. It appears to be necessary to design more effective regimen.