Viju Bhadkamkar

PCA3 Molecular Urine Assay Correlates With Prostate Cancer Tumor Volume: Implication in Selecting Candidates for Active Surveillance

PURPOSE Prostate cancer gene 3 (PCA3) has shown promise as a molecular marker in prostate cancer detection. We assessed the association of urinary PCA3 score with prostatectomy tumor volume and other clinical and pathological features. MATERIALS AND METHODS Urine specimens were collected after digital rectal examination from 59 men scheduled for prostate biopsy and 83 men scheduled for radical prostatectomy. Prostatectomy findings were evaluable for 96 men. PCA3 and prostate specific antigen mRNAs were quantified with Gen-Probe DTS 400 System. The PCA3 score was defined as the ratio of PCA3 mRNA/prostate specific antigen mRNA x10(3). RESULTS The PCA3 score in men with negative biopsies (30) and positive biopsies (29) were significantly different (median 21.1 and 31.0, respectively, p = 0.029). The PCA3 score was significantly correlated with total tumor volume in prostatectomy specimens (r = 0.269, p = 0.008), and was also associated with prostatectomy Gleason score (6 vs 7 or greater, p = 0.005) but not with other clinical and pathological features. The PCA3 score was significantly different when comparing low volume/low grade cancer (dominant tumor volume less than 0.5 cc, Gleason score 6) and significant cancer (p = 0.007). On multivariate analysis PCA3 was the best predictor of total tumor volume in prostatectomy (p = 0.001). Receiver operating characteristic curve analysis showed that the PCA3 score could discriminate low volume cancer (total tumor volume less than 0.5 cc) well with area under the curve of 0.757. CONCLUSIONS The PCA3 score appears to stratify men based on prostatectomy tumor volume and Gleason score, and may have clinical applicability in selecting men who have low volume/low grade cancer.

Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors.

PURPOSE The purpose of this phase I trial was to determine the toxicity and maximum-tolerated dose (MTD) of murine monoclonal antibody (Mab) 14G2a (anti-GD2) in cancer patients. PATIENTS AND METHODS Following tracer doses of iodine-131-labeled 14G2a to determine tumor uptake, 18 patients with refractory melanoma, neuroblastoma, or osteosarcoma received unlabeled 14G2a at total concentrations of 50, 100, and 200 mg/m2 administered as daily 24-hour infusions for 5 days. RESULTS The overall sensitivity of external immunoscintigraphy was 64 of 74 known metastases (86%). Toxicity from prolonged infusion of 14G2a consisted of severe generalized pain, hyponatremia, fever, rash, paresthesias, weakness, and chronic refractory postural hypotension (two patients). Toxicity was less severe in pediatric patients. The MTD of Mab was 100 mg/m2. Sixteen of 18 patients developed human antimouse antibodies (HAMA) to 14G2a. Terminal-phase half-life (T1/2) of unlabeled Mab was 6.6 +/- 1.8 hours for patients receiving 50 mg/m2 and 39.5 +/- 13.3 hours at the 100-mg/m2 level. Tumor biopsies from six melanoma patients were positive for GD2 antigen, but only two of six had trace amounts of 14G2a present. Three mixed responses (two melanoma, one osteosarcoma) and two partial responses (PRs; neuroblastoma) were observed. CONCLUSION Mab 14G2a has modest antitumor activity at the expense of significant toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other than in pediatric patients with neuroblastoma.

Circulating Tumor Cells in Peripheral Blood Samples From Patients With Increased Serum Prostate Specific Antigen: Initial Results in Early Prostate Cancer

PURPOSE We evaluated the hypothesis that circulating tumor cells as determined using the CellSearch System would correlate with tumor volume, pathological stage and Gleason score in men with localized prostate cancer. MATERIALS AND METHODS Samples of blood (30 ml) were drawn from 97 men with localized prostate cancer before radical prostatectomy, on postoperative days 2 to 3 and at 6 weeks. A control group consisted of 25 men with an increased prostate specific antigen and no tumor detected on extended prostate biopsy. Samples were analyzed for circulating tumor cells using the CellSearch System. RESULTS Circulating tumor cells were detected in 21% of patients with cancer and 20% of controls (p = 0.946). At 6 weeks after prostatectomy circulating tumor cells were detected in 16% and 11% (p = 0.51) of the men positive and negative for circulating tumor cells at baseline, respectively. Of the 20 patients with cancer who had circulating tumor cells at baseline 18 showed no circulating tumor cells after surgery. Circulating tumor cell values did not correlate with tumor volume, pathological stage or Gleason score. Only 3.1% of the men with cancer and 8% of the control group had 3 or more circulating tumor cells per 22.5 ml blood at baseline. CONCLUSIONS In metastatic breast, prostate and other cancers more than 5 circulating tumor cells are often detected using the CellSearch System, and may correlate with prognosis. However, in the setting of localized prostate cancer the number of detectable circulating tumor cells was low, with findings comparable to those in men who were biopsy negative for cancer. We found no correlation between the number of circulating tumor cells and known prognostic factors in this population.

Outcome Of Patients With Gleason Score 8 Or Higher Prostate Cancer Following Radical Prostatectomy Alone

PURPOSE We determine the effect of clinical and pathological variables on the outcome of patients with prostate cancer of Gleason scores 8 or greater treated with radical prostatectomy alone. MATERIALS AND METHODS Between April 1987 and October 1998, 1,199 patients underwent radical retropubic prostatectomy. We identified 188 patients assigned a Gleason score of 8 or higher in the prostatectomy specimen who did not receive any neoadjuvant or adjuvant therapy. Median followup was 60 months (range 1 to 129). Disease recurrence was defined as any detectable prostate specific antigen level 0.1 ng./ml. or greater. RESULTS Of 188 patients 128 (68%) had no evidence of prostate cancer after a median followup of 60 months, while 60 (32%) demonstrated a detectable PSA level. There were 58 (31%) patients with disease confined to the prostate with negative surgical margins while 108 (57%) had prostate cancer confined to the surgical specimen. Positive surgical margin with extraprostatic extension was seen in 16 (9%) patients and seminal vesicle invasion was present in 40 (21%). The 5 and 7-year disease-free survival rates for the entire cohort were 71% and 55%, respectively. Patients with specimen confined disease had a significantly higher 5-year disease-free survival rate than those with nonspecimen confined disease (84% and 50%, p <0.0001). On multivariate analysis pathological status of the surgical specimen was the most significant independent predictor of disease recurrence. Age, ethnicity, clinical stage and preoperative PSA had no independent effect on disease recurrence. CONCLUSIONS Long-term disease-free survival can be expected in those patients with high grade prostate cancer whose disease is confined to the prostate and/or the surgical specimen.

Natural History of Biochemical Progression After Radical Prostatectomy Based on Length of a Positive Margin

OBJECTIVES To assess the effect of length of positive margin on prognosis in men after radical prostatectomy. METHODS The positive surgical margin without either seminal vesicle invasion or lymph node metastases was identified in 117 men undergoing prostatectomy between 1991 and 1999. The length of positive margin was obtained by adding together the lengths of all areas of the tumor in contact with the inked surface. Biochemical failure was defined as a serum prostate specific antigen level 0.1 ng/mL or greater. Statistical analyses were performed to compare times with progression and to determine factors for progression. RESULTS The median follow-up duration was 43 months, and the overall 5-year progression-free survival (PFS) rate was 74.6%. The differences in prognoses between men with a positive margin 1 mm or less and those with a margin 1.1 to 3 mm was not significant; however, there was a significant difference in prognosis between men with a margin 3 or less and those with a margin greater than 3 mm (P <0.01). Multivariate analyses revealed that both Gleason score 8 or greater and a margin 3 mm or greater were independent predictors. The prognoses in men with neither of these risk factors was statistically better than that of men with either or both of these risk factors (5-year PFS rates 93% versus 57%, respectively; P <0.0001). CONCLUSIONS The length of positive margin is significantly associated with disease progression. The Gleason score and the extent of positive margin can be used to stratify the risk for recurrence in patients with positive margin.

Value of SPECT imaging of the thoracolumbar spine in cancer patients.

The purpose of this study was to evaluate the usefulness of SPECT bone imaging in targeting the precise location of vertebral abnormalities to ascertain whether such knowledge would help in differentiating between metastatic and benign lesions. SPECT images of the thoracolumbar spine in 50 patients were correlated with plain x-rays, CT, MRI, PET, and bone scans and 6-month clinical follow-ups. SPECT images revealed 110 lesions, 35 of which were metastases. Twenty-four of 25 lesions involving the vertebral body with extension into posterior elements were metastases, as well as 10 of 39 lesions found in the vertebral-body and 1 of 4 found in the spinous process. All lesions limited to the anterior aspect of the vertebral body (13/13), facet joints (23/23), and intervertebral disk space (6/6) were benign. In conclusion, SPECT imaging of the thoracolumbar spine is helpful in determining the precise anatomic location of vertebral abnormalities, and knowledge of the location can be used to determine whether these abnormalities in cancer patients are benign entities or metastases.

Phase II radioimmunotherapy trial with131I-CC49 in colorectal cancer

Background. Radiolabeled CC49, a second generation high affinity monoclonal antibody (MoAb) reactive with tumor‐associated glycoprotein 72 (TAG72) has undergone previous Phase I testing in patients with colon cancer. Based on this report, the authors treated 15 refractory metastatic colon cancer patients with 131I‐CC49 to determine its overall toxicity and the response to therapy of patients treated with it.