Ten-year biochemical disease control for patients with prostate cancer treated with cryosurgery as primary therapy.

OBJECTIVES: Prostate cryosurgery has been increasingly used for the management of localized prostate cancer since its introduction in a minimally invasive form in the early 1990s. We performed a retrospective study of the largest and most mature patient group treated with cryosurgery reported thus far. METHODS: We retrospectively analyzed the data from 370 patients treated consecutively from 1991 to 1996 with a focus on the determination of biochemical disease-free survival for a group of patients with T1 to T3 prostate cancer who had undergone prostate cryosurgery as primary monotherapy. Only patients with no previous radiotherapy, hormonal therapy, or surgery were included. RESULTS: The median follow-up was 12.55 years. Using a nadir plus 2 ng/dL definition, Kaplan-Meier analysis demonstrated a biochemical disease-free survival rate at 10 years of 80.56%, 74.16%, and 45.54% for low, moderate, and high-risk groups, respectively. The 10-year negative biopsy rate was 76.96%. CONCLUSIONS: The results for this pilot group of patients who underwent percutaneous prostate cryosurgery monotherapy demonstrated biochemical disease-free survival rates that overlap with those of similar groups of patients treated under similar circumstances using other types of nonextirpative monotherapy.

Calcitriol (1,25-dihydroxycholecalciferol) potentiates activity of mitoxantrone/dexamethasone in an androgen independent prostate cancer model.

PURPOSE: Mitoxantrone combined with glucocorticoids is widely used for androgen independent prostate cancer. It is well tolerated, reduces prostate specific antigen, diminishes pain and improves quality of life. Calcitriol (1,25-dihydroxycholecalciferol) inhibits proliferation, modulates cell cycle progression, induces apoptosis and potentiates the cytotoxic effects of a number of agents. Glucocorticoids potentiate the antitumor effects of calcitriol and blunt calcitriol induced hypercalcemia. Therefore, we investigated the effect of calcitriol on the antitumor efficacy of mitoxantrone and dexamethasone or mitoxantrone/dexamethasone in the PC-3 androgen independent prostate cancer model. MATERIALS AND METHODS: We treated PC-3 cells in vitro with various concentrations of mitoxantrone/dexamethasone with and without calcitriol, and assessed growth inhibition by crystal violet assays. We similarly treated mice bearing PC-3 xenografts and performed excision clonogenic assays and tumor outgrowth studies to assess antitumor activity. RESULTS: Calcitriol significantly increased mitoxantrone/dexamethasone mediated growth inhibition in PC-3 cells (p <0.05). Median dose effect analysis indicated that calcitriol is synergistic with mitoxantrone. Adding calcitriol to mitoxantrone/dexamethasone significantly reduced the surviving fraction per gm. tumor compared with mitoxantrone/dexamethasone or untreated controls (p <0.03). Calcitriol plus mitoxantrone/dexamethasone also caused significantly greater tumor regression in PC-3 xenografts compared with treatment with mitoxantrone/dexamethasone or untreated controls (p <0.02). CONCLUSIONS: These preclinical data demonstrate that calcitriol increases the antitumor activity of mitoxantrone/dexamethasone in the PC-3 model system. This combination may be efficacious for prostate cancer.

Mammographically Occult Breast Cancers.

A small percentage of breast cancers are not visible on mammography. Since mammographically occult malignancies may be more difficult to diagnose, we hypothesized that the lack of visualization would cause a delay in detection, more aggressive surgical and adjuvant therapy, and poorer outcome. Patients with mammographically occult malignancies were compared to patients with cancers visible on mammogram. The significance of mammographic visibility for treatment and local and distant recurrence rates were evaluated. Ninety-one of the 813 (11%) cancers were mammographically occult. Patients with mammographically occult malignancies were significantly younger, of lower body weight, and had fewer pregnancies than patients with cancers visible on mammography: age, body weight, and parity were statistically significant (p < 0.001) in stepwise logistic regression. Ductal carcinoma in situ was significantly more frequently diagnosed in patients with mammographically visible malignancies (14% versus 4%, p = 0.0163) and nodal involvement was significantly more frequent in patients with mammographically occult malignancies (35% versus 24%, p = 0.0391). Diagnostic delays exceeding 3 months were experienced by 24% of patients with mammographically occult malignancies compared to 13% of patients with tumor visible on mammography (p < 0.0001). Adjuvant chemotherapy was given to 63% of patients with occult malignancies compared to 41% of patients with mammographically visible cancers (p = 0.0027). The use of breast-conserving therapy and adjuvant radiation and tamoxifen were comparable. Survival free of local recurrence and distant metastases for the 403 patients followed for 5 years or more was not related to mammographic visibility.