Primary androgen deprivation (AD) followed by active surveillance (AS) for newly diagnosed prostate cancer (PC): A retrospective study.

BACKGROUND: Active surveillance (AS) is only recommended for Low-Risk prostate cancer (PC) with <34% biopsies positive. Studies describing the long-term outcome of men treated with androgen deprivation (AD) followed by AS are sparse. MATERIALS AND METHODS: One hundred two men were treated with 12 months of AD in a medical oncology clinic specializing in PC between 1998 and 2007 and were followed for a median of 7.25 years. The biopsy complete response rate after AD and the incidence of disease progression while on subsequent AS was assessed. Baseline age, D'Amico risk category, PSA velocity, percentage core biopsies, and prostate volume were evaluated as potential predictors of disease progression. RESULTS: D'Amico risk category for the 102 men: Low: n = 22, Intermediate: n = 30, and High: n = 50. Medians: Age 67.3, PSA 7.8, Gleason 3 + 4, >50% core biopsies positive, stage T1c. Seventy men had a clear biopsy and 31 of these had disease progression leading to additional treatment after a median of 52 months. D'Amico risk category of the 57 men with a positive biopsy after AD or disease progression on AS was: Low: n = 4 (18%), Intermediate: n = 16 (53%), and High: n = 37 (74%). No PC deaths occurred. Three men had clinical progression. In stepwise logistic regression analysis only higher D'Amico risk category and lower prostate volume predicted disease progression. CONCLUSIONS: Despite a high prevalence of ≥50% core biopsies positive at baseline, AD induces durable remissions in most men with Low-Risk and about half with Intermediate-Risk PC.

Case report: Sodium dichloroacetate (DCA) inhibition of the "Warburg Effect" in a human cancer patient: complete response in non-Hodgkin's lymphoma after disease progression with rituximab-CHOP.

The uptake of fluorodeoxyglucose Positron Emission Tomography in the tumors of various cancer types demonstrates the key role of glucose in the proliferation of cancer. Dichloroacetate is a 2-carbon molecule having crucial biologic activity in altering the metabolic breakdown of glucose to lactic acid. Human cell line studies show that dichloroacetate switches alter the metabolomics of the cancer cell from one of glycolysis to oxidative phosphorylation, and in doing so restore mitochondrial functions that trigger apoptosis of the cancer cell. Reports of dichloroacetate in human subjects are rare. The authors contacted individuals from Internet forums who had reported outstanding anti-cancer responses to self-medication with dichloroacetate. With informed consent, complete medical records were requested to document response to dichloroacetate, emphasizing the context of monotherapy with dichloroacetate. Of ten patients agreeing to such an evaluation, only one met the criteria of having comprehensive clinic records as well as pathology, imaging and laboratory reports, along with single agent therapy with dichloroacetate. That individual is the focus of this report. In this case report of a man with documented relapse after state-of-the-art chemotherapy for non-Hodgkin's lymphoma, a significant response to dichloroacetate is documented with a complete remission, which remains ongoing after 4 years. Dichloroacetate appears to be a novel therapy warranting further investigation in the treatment of cancer.

Optimized 18F-FDG PET-CT Method to Improve Accuracy of Diagnosis of Metastatic Cancer.

The diagnosis of cancer by FDG PET-CT is often inaccurate owing to subjectivity of interpretation. We compared the accuracy of a novel normalized (standardized) method of interpretation with conventional non-normalized SUV. Patients (n = 393) with various malignancies were studied with FDG PET/CT to determine the presence or absence of cancer. Target lesions were assessed by two methods: (1) conventional SUVmax (conSUVmax) and (2) a novel method that combined multiple factors to optimize SUV (optSUVmax), including the patient's normal liver SUVmax, a liver constant (k) derived from a review of the literature, and use of site-specific thresholds for malignancy. The two methods were compared to pathology findings in 154 patients being evaluated for mediastinal and/or hilar lymph node (MHLNs) metastases, 143 evaluated for extra-thoracic lymph node (ETLNs) metastases, and 96 evaluated for liver metastases. OptSUVmax was superior to conSUVmax for all patient groups. For MHLNs, sensitivity was 83.8% vs. 80.7% and specificity 88.7% vs. 9.6%, respectively; for ETLNs, sensitivity was 92.1% vs. 77.8% and specificity 80.1% vs. 27.6%, respectively; and for lesions in the liver parenchyma, sensitivity was 96.1% vs. 82.3% and specificity 88.8% vs. 23.0%, respectively. Optimized SUVmax increased diagnostic accuracy of FDG PET-CT for cancer when compared with conventional SUVmax interpretation.

Primary intermittent androgen deprivation as initial therapy for men with newly diagnosed prostate cancer.

BACKGROUND: The purpose of this study was to describe the long-term incidence of cancer progression and mortality in men with localized prostate cancer treated with primary androgen deprivation (AD). METHODS: A retrospective chart review, from a medical oncology practice specializing in prostate cancer, was conducted of 73 men eligible for surgery or radiation treated with induction AD. Entry criteria consisted of a minimum of 9 months of induction AD, treatment initiation before 1999, clinical stage < T3, and outcome defined as the incidence of delayed local therapy, cancer progression, cancer mortality, and mortality from other causes. RESULTS: Median follow-up was 12 years. Fifteen men were at low risk, 38 were at intermediate risk, and 20 were at high risk. Three men (4%) experienced metastatic disease and died of prostate cancer after 3.5, 7.7, and 11 years, respectively. Two men were in the intermediate-risk category and 1 was high risk. Nineteen men (26%) died of non-prostate cancer causes. None had metastatic disease at the time of death. Of the remaining 51 survivors, none has experienced bone metastasis. Twenty-one men (29%) required no further therapy after the first induction course of AD. Twenty-four men (33%) maintained a prostate-specific antigen (PSA) level < 5.0 ng/mL with 2 to 5 cycles of intermittent AD. Twenty-eight men (38%) underwent delayed local therapy after a median of 5.5 years. Median follow-up after local therapy was 6.2 years. Three of these men experienced subsequent rising PSA levels but none has progressed to bone metastasis. Sixteen of 20 men (80%) in the high-risk category but only 12 of 53 men (23%) in the low- and intermediate-risk categories had delayed local therapy. CONCLUSIONS: Primary intermittent AD is feasible for men with localized prostate cancer. Men who are younger and men with high-risk disease undergo delayed local therapy more frequently.

Intermittent use of testosterone inactivating pharmaceuticals using finasteride prolongs the time off period.

PURPOSE: Men with prostate cancer treated intermittently with TIP benefit from improved quality of life when TOP with recovered testosterone is prolonged. We examined factors influencing the duration of TOP. MATERIALS AND METHODS: We retrospectively reviewed the charts of 101 men treated with intermittent TIP in a 9-year period. Men with positive bone scan, men in whom a PSA nadir of less than 0.1 ng/ml on TIP failed to be achieved and maintained and men in whom testosterone failed to recover to greater than 150 ng/dl during the first 12 months of TOP were excluded. Potential factors predicting prolonged TOP or accelerated time to AIPC were studied with Cox regression analysis. RESULTS: Patient characteristics were clinical stage T1c-T2a in 51 and T2b-T3b in 11, PSA relapse in 29, and T3c, D0 or D1 in 10. Median PSA was 7.6 ng/ml, Gleason score was 3 + 4 = 7 and TIP duration was 15.8 months. The 60 group 1 patients received finasteride and the 41 in group 2 received no finasteride. Median TOP in groups 1 and 2 was 31 and 15 months, respectively, using Kaplan-Meier analysis. Cox regression analysis indicated that longer TIP, finasteride and increased age predicted longer TOP. A slow PSA decrease while on TIP, higher baseline PSA and increased Gleason score predicted shorter TOP. Cox regression analysis indicated that only higher clinical stage but not finasteride predicted the earlier onset of AIPC. CONCLUSIONS: Finasteride doubles the duration of TOP. AIPC was not increased by finasteride after almost 9 years of observation.