capromab-pendetide and Adenocarcinoma

The provision of accurate prognostic information is a long-standing goal for effective management of prostate adenocarcinoma. Nontargeted imaging modalities are less efficient at detecting slow-growing prostate cancers. Prostate-specific membrane antigen has emerged as a superior biomarker, especially for the evaluation of metastatic spread. Advances in imaging technology have focused clinical interest on indium-111 capromab ((111)In capromab) pendetide, a radioimmunoconjugate that detects prostate-specific membrane antigen expression in vivo. Single-photon emission computed tomography capromab pendetide images, fused with those generated by computed tomography or magnetic resonance, have engendered improvements in localization accuracy by correlating high signal intensity with anatomic structures. In long-term outcomes studies, fused (111)In capromab pendetide scans have delivered significant benefits for patient selection and improved treatment of prostate cancer.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Combined Modality Therapy; Humans; Immunohistochemistry; Indium Radioisotopes; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Sensitivity and Specificity; Survival Analysis; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Capromab Pendetide imaging illustrates the successful translation of monoclonal antibody technology from the laboratory to the clinic. It provides a means of identifying otherwise occult soft tissue metastases in patients with adenocarcinoma of the prostate. When utilized with other clinical, pathological and laboratory findings, Capromab Pendetide imaging enables more accurate disease staging and monitoring than is afforded by other imaging modalities such as CT and MRI. In the primary disease setting Capromab Pendetide imaging should be reserved for use in patients with negative bone scans who are at high risk for metastatic disease based on such factors as advanced clinical stage, high Gleason score and significantly elevated serum PSA or alkaline phosphatase. Due to low sensitivity for small-volume disease, a negative Mab scan may not eliminate the need for a staging lymph node dissection but should encourage further consideration of local treatment options. Capromab Pendetide should be used with caution in patients at low risk for metastatic disease. Positive scan findings in low risk patients should be confirmed before altering the treatment plan since some false positive scans should be anticipated in a population with low disease prevalence. Capromab Pendetide imaging has not been shown to be reliable in determining the local extent of the primary tumor but new techniques involving co-registration of SPECT and CT images show promise in this regard. In the patient with recurrent disease following primary therapy, the predictive value of Capromab Pendetide imaging of the prostate or prostate fossa is limited, particularly following RT. Its more important role in this setting is to identify lymph node metastases in the high risk patient with a negative bone scan who might otherwise be a candidate for local salvage therapy. A large prospective study is needed for confirmation, but preliminary data suggest that Capromab Pendetide imaging is helpful in identifying those patients with PSA elevation after radical prostatectomy who are most likely to benefit from salvage RT. As with any imaging technique, Capromab Pendetide has strengths and weaknesses that must be understood to maximize patient benefit by utilizing the scan in clinical settings where it is most likely to be useful and least likely to be misleading. Capromab Pendetide is a technically demanding procedure best performed and interpreted at sites with experience and expertise.

Topics: Adenocarcinoma; Alkaline Phosphatase; Antibodies, Monoclonal; Biomarkers, Tumor; Bone Neoplasms; Combined Modality Therapy; Evaluation Studies as Topic; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm, Residual; Preoperative Care; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radioimmunodetection; Radioisotope Teletherapy; Salvage Therapy; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Diagnostic methods are limited for detecting microscopic soft tissue metastases in patients with prostate cancer. Previous studies using (111)Indium Capromab Pendetide (ProstaScint scan) analyzed patients with extensive localized tumor (prostate specific antigen (PSA) >20 ng/ml) not optimal for surgical therapy. We evaluated the role of the ProstaScint trade mark scan in a preoperative population to provide histological documentation and to assess its utility in a surgical population. A total of 22 preoperative patients, underwent a ProstaScint scan. The mean preoperative PSA was 16.0 ng/ml (range 3.9-33 ng/ml). The mean Gleason score at biopsy was 6.9 (range 6-9). Each patient underwent a radical retropubic prostatectomy and bilateral pelvic lymph node dissection, which included resection of both obturator and common iliac lymph nodes. Histologic analysis of the resected lymph nodes provided the standard of comparison with the ProstaScint scan. The results of the scan and pathology for all 22 patients were compared with the bilateral obturator and iliac nodes, creating 88 data points. Nine areas (10%) were positive on the scan. One of these (11%) was a true positive while the other eight (89%) were false positives. Seventy-nine areas (90%) were negative on scan results. Of these, five areas (6%) were false negatives and 74 areas (94%) were true negatives. The scan yielded a sensitivity of 17%, specificity of 90%, negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 11%. The high false positive rate and low PPV of ProstaScint scans overestimates metastatic lymph nodes disease, and is not useful when used preoperatively.

Topics: Adenocarcinoma; Antibodies, Monoclonal; False Positive Reactions; Humans; Indium Radioisotopes; Lymphatic Metastasis; Male; Neoplasm Staging; Predictive Value of Tests; Preoperative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Sensitivity and Specificity

No standard noninvasive diagnostic test reliably differentiates patients with organ-confined prostate cancer from those with lymph node metastases. The ability of a radiolabeled monoclonal antibody, indium-111 (111ln)-capromab pendetide, to identify sites of metastatic disease in patients at moderate to high risk of nodal involvement was investigated.. The study prospectively evaluated 160 patients with prostate cancer scheduled to undergo pelvic lymph node dissection (PLND) before or during definitive treatment. All were at relatively high risk of nodal involvement by virtue of significantly elevated baseline prostate-specific antigen (PSA) values, Gleason scores, and/or locally advanced clinical stages of disease. The histologic findings of the PLNDs were compared with the results of immunoscintigraphy, computed tomography, and magnetic resonance imaging.. Among the 152 evaluable patientS studied with 111In-capromab pendetide before PLND, the sensitivity of immunoscintigraphy for lymph node detection was 62% and the specificity was 72%; the positive predictive value was 62% and the negative predictive value was 72%. In comparison, the sensitivity of computed tomography and magnetic resonance imaging was 4% and 15%, respectively, and the specificity was 100% for both procedures on the basis of a large number of negative interpretations. Logistic regression analysis revealed that immunoscintigraphy with 111In-capromab pendetide provided strong, independent evidence of the presence of lymph node metastases. Furthermore, the analysis indicated that certain combinations of PSA, Gleason score, and 111In-capromab pendetide were particularly effective at predicting the risk of nodal involvement.. Immunoscintigraphy with 111In-capromab pendetide outperformed standard diagnostic imaging techniques in the detection of prostate cancer lymph node metastases and provided independent prognostic information that complemented PSA, Gleason score, and clinical stage.

Topics: Adenocarcinoma; Aged; Algorithms; Antibodies, Monoclonal; Humans; Indium Radioisotopes; Logistic Models; Male; Middle Aged; Preoperative Care; Prospective Studies; Prostatic Neoplasms; Radioimmunodetection; Sensitivity and Specificity

There is currently no curative therapy for men who have disseminated prostate cancer following failed radical prostatectomy. The purpose of this trial was to investigate systemic radioimmunotherapy in these men. Eight patients with occult metastatic prostate cancer following radical prostatectomy as evidenced solely by a rising serum PSA and evidence of soft tissue lesions outside the prostatic fossa detected by an [111I]indiumcapromab pendetide scan received an infusion of 10 mg of capromab pendetide labeled with 9 mCi/m2 of [90Y]yttrium. Serum PSA was used to measure response rate. There were no complete or partial responses by PSA criteria. Significant unexpected bone marrow toxicity developed in the first 6 of 8 patients treated. The last two patients received co-infusion of edetate calcium disodium in an effort to decrease marrow suppression. In these two patients less marrow toxicity was seen. Repeat 111In-capromab pendetide scans were uninterpretable due to grossly altered whole-body biodistribution of the radioimmunoconjugate. Retrospective analysis of serial PSA values after closure of the study showed a decrease in the log slope PSA for seven of eight patients following radioimmunotherapy, with a statistically significant change in the mean log slope (p = 0.01). The clinical significance of this small but measurable change is uncertain. We conclude that radioimmunotherapy for occult metastatic prostate cancer using 90Y-capromab-pendetide at the dose described does not lower serum PSA, is associated with significant hematologic toxicity, and leads to complexation of the immunoconjugate following subsequent capromab pendetide infusion.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Marrow; Combined Modality Therapy; Edetic Acid; Gonadotropin-Releasing Hormone; Humans; Immunoconjugates; Leukopenia; Male; Middle Aged; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiation Injuries; Radioimmunodetection; Salvage Therapy; Soft Tissue Neoplasms; Thrombocytopenia; Tissue Distribution; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Treatment Failure; Treatment Outcome; Yttrium Radioisotopes

A study using monoclonal antibody ProstaScint was conducted to determine the role of radioscintigraphy for evaluation of patients with adenocarcinoma of the prostate. Previous evaluations determining sensitivity and toxicity for this agent were conducted in a multicenter study.. ProstaScint scans were used for preoperative staging in patients presumed to be candidates for total prostatectomy and a subsequent study was performed for the detection and localization of recurrent prostate cancer following definitive therapy.. The monoclonal antibody scan detected localized recurrent cancer in 43 patients who were possible candidates for external beam radiation therapy.. The monoclonal antibody conjugate ProstaScint provides additional information in detection and localization of recurrent prostate cancer and would be helpful in the selection of patients for subsequent external beam radiation therapy.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Care; Preoperative Care; Prostatic Neoplasms; Radionuclide Imaging

The utility of monoclonal antibody (MAb) imaging for detection of occult recurrent prostate cancer was investigated in 14 patients with elevated serum prostate-specific antigen at least 3 months after therapy. All were imaged with capromab pendetide (CYT-356) and subsequently had biopsies of the prostate bed. Ten also had PET scans with F-18 fluorodeoxyglucose. Ten MAb scans were positive for tumor in the prostate bed and eight showed lymph node metastases. Six of the seven patients with positive biopsies had positive MAb scans, one had a negative scan. Three of the seven patients with negative biopsies had negative MAb scans, four had positive scans. Of the six patients with positive biopsies who had PET scans, one was positive, five were negative. Two of four patients with negative biopsies had negative positron emission tomography scans, two were positive. MAb imaging is superior to PET scan for identifying recurrent disease in the prostate bed. Assuming no false-negative biopsies, the positive predictive values for MAb and PET scan are 60% and 33%, negative predictive values are 75% and 29% and sensitivities are 86% and 17%. Additional investigation is necessary to determine if MAb uptake in lymph nodes is predictive of metastatic disease.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy, Needle; Humans; Indium Radioisotopes; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Neoplasm, Residual; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunodetection; Sensitivity and Specificity; Tomography, Emission-Computed; Tomography, Emission-Computed, Single-Photon

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Humans; Lung Neoplasms; Male; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radionuclide Imaging; Radiopharmaceuticals

We evaluate the usefulness of pretreatment (111)Indium capromab pendetide (ProstaScint) planar imaging (immunoscintigraphy) plus single photon emission tomography co-registration with computerized tomography scans to detect occult metastatic disease and predict for biochemical failure, in a cohort of patients with a clinical diagnosis of localized adenocarcinoma of the prostate referred for primary radiotherapy.. Patients were followed after radiotherapy for evidence of biochemical failure using 2 criteria of prostate specific antigen clinical nadir +2 ng/ml and American Society for Therapeutic Radiology and Oncology Consensus definitions. Median followup was 58.8 months (mean 64.8). Clinical risk factors defined 3 risk groups of high (51), intermediate (72) and low (116).. Overall biochemical failure was 18.3% vs 11.8% by the 2-BFC at 8-year actuarial analysis with 58.8 months median followup. By the CN +2 definition the control date for the cohort is 34.8 months. Pretreatment SPECT/CT suggested prostate cancer metastasis (22), seminal vesicle extension (20) and organ confined disease (197). Biochemical failure in patients having extra-periprostatic metastatic prostate cancer, seminal vesicle extension and organ confined disease uptake on SPECT/CT was 43.2%, 16.0% vs 14.7% (p = 0.0006); and 33.3%, 15.0% vs 8.7% (p = 0.0017) by the 2-BFC, respectively. Cox multiple regression analysis demonstrated that a finding of extra-periprostatic metastatic prostate on SPECT/CT significantly predicted a 4.2-fold greater risk (p = 0.0012) and a 4.5-fold greater risk (p = 0.0011) of failure by the 2-BFC than organ confined disease adjusting for treatment and risk group.. Unconfirmed findings of extra-periprostatic metastatic prostate cancer on SPECT/CT immunoscintigraphy independently and significantly predicted an increased risk of biochemical failure in patients presenting for radiotherapy with a clinical diagnosis of localized prostate cancer.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Brachytherapy; Humans; Indium Radioisotopes; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunodetection; Radiotherapy Dosage; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed

ProstaScint (CYT-356 or capromab pendetide, Cytogen) is an 111In-labeled monoclonal mouse antibody specific for prostate-specific membrane antigen, a prostate transmembrane glycoprotein that is upregulated in prostate adenocarcinoma. ProstaScint scans are US Food and Drug Administration approved for pretreatment evaluation of metastatic disease in high-risk patients. They are also approved for post-prostatectomy assessment of recurrent disease in patients with a rising prostate-specific antigen level. This review explores the literature on ProstaScint and its use in guiding the treatment of prostate cancer. A novel technique for identifying areas of cancer within the prostate using ProstaScint images fused with pelvic computed tomography scans is also described. The identification of areas of high antibody signal provides targets for radiotherapeutic dose escalation, with the overall goals of improving treatment outcome while preserving adjacent tissue structures and decreasing treatment morbidity.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Brachytherapy; Humans; Indium Radioisotopes; Male; Mice; Prostatic Neoplasms; Tomography, X-Ray Computed; Treatment Outcome

We have previously presented a technique that fuses ProstaScint and pelvic CT images for the purpose of designing brachytherapy that targets areas at high risk for treatment failure. We now correlate areas of increased intensity seen on ProstaScint-CT fusion images to biopsy results in a series of 7 patients to evaluate the accuracy of this technique in localizing intraprostatic disease.. The 7 patients included in this study were evaluated between June 1998 and March 29, 1999 at Metrohealth Medical Center and University Hospitals of Cleveland in Cleveland, Ohio. ProstaScint and CT scans of each patient were obtained before transperineal biopsy and seed implantation. Each patient's prostate gland was biopsied at 12 separate sites determined independently of Prostascint-CT scan results.. When correlated with biopsy results, our method yielded an overall accuracy of 80%: with a sensitivity of 79%, a specificity of 80%, a positive predictive value of 68%, and a negative predictive value of 88%.. The image fusion of the pelvic CT scan and ProstaScint scan helped identify foci of adenocarcinoma within the prostate that correlated well with biopsy results. These data may be useful to escalate doses in regions containing tumor by either high-dose rate or low-dose rate brachytherapy, as well as by external beam techniques such as intensity modulated radiotherapy (IMRT).

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy; Humans; Indium Radioisotopes; Male; Prospective Studies; Prostate; Prostatic Neoplasms; Radioimmunodetection; Sensitivity and Specificity; Tomography, X-Ray Computed

Topics: Adenocarcinoma; Algorithms; Antibodies, Monoclonal; Combined Modality Therapy; Evaluation Studies as Topic; False Negative Reactions; Humans; Logistic Models; Lymphatic Metastasis; Male; Multicenter Studies as Topic; Predictive Value of Tests; Preoperative Care; Prostatectomy; Prostatic Neoplasms; Radioimmunodetection; Risk; Salvage Therapy; Tomography, Emission-Computed, Single-Photon

A 59-year-old man presented with a Gleason score of 4 + 4 = 8 prostate cancer and with multiple bilateral pelvic nodes involved at open pelvic lymph node dissection. On indium-111 capromab pendetide (ProstaScint) scan, there was increased tracer deposition in the prostate, the mesenteric nodes, the right pulmonary hilum, and the left supraclavicular fossa. The ProstaScint injection was repeated, and the gamma probe was used to localize tissue that accumulated radiotracer. Two nodes were excised, one that exhibited increased uptake and one that did not. The radioactive lymph node contained metastatic prostate cancer. No malignancy was found in the second node.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Biopsy; Humans; Indium Radioisotopes; Lymphatic Metastasis; Male; Middle Aged; Neck; Pelvis; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging

We present a technique that fuses pelvic CT scans and ProstaScint images to localize areas of disease within the prostate gland to customize prostate implants. Additionally, the acute toxicity results from the first 43 patients treated with this technique are reviewed.. Between 2/97 and 8/98, 43 patients with clinical stage II prostate adenocarcinoma received ultrasound-guided transperineal implantation of I-125 or Pd-103 seeds. The median patient age was 70 years (range 49-79). Prior to treatment, the median Gleason score and prostate-specific antigen (PSA) were 6 (range 3-8) and 7.5 (range 1.8-16.6 ng/mL), respectively. The median follow-up was 10 months (range 2.9-20.4 months).. The median PSA value at 10 months is 0.7 ng/mL. Significant acute complications within the first month following implantation included 13 Grade I urinary symptoms, 24 Grade II urinary symptoms, 6 Grade III symptoms, and no Grade IV complications. Beyond 4 months, complications included 12 Grade I urinary symptoms, 17 Grade II urinary symptoms, 1 Grade III, and 1 Grade IV complications.. The image fusion of the pelvic CT scan and ProstaScint scans helped identify regions within the prostate at high risk of local failure, which were targeted with additional seeds during implantation.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Brachytherapy; Feasibility Studies; Follow-Up Studies; Humans; Indium Radioisotopes; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Tomography, X-Ray Computed; Urination Disorders

Topics: Adenocarcinoma; Antibodies, Monoclonal; Bone Neoplasms; Humans; Indium Radioisotopes; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radiopharmaceuticals; Technetium Tc 99m Medronate; Tomography, Emission-Computed, Single-Photon

Topics: Adenocarcinoma; Antibodies, Monoclonal; Diagnosis, Differential; False Positive Reactions; Humans; Indium Radioisotopes; Kidney; Lymphatic Metastasis; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms; Radioimmunodetection; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon

To provide appropriate therapy for prostate cancer, accurate staging of the patient's disease is essential. Determination of tumor size, location, periprostatic extension and metastatic disease in the skeleton and soft tissue are needed to stage properly. Current diagnostic modalities may lead to understaging in 40%-70% of prostate cancer. Detection of metastatic disease, both at the time of initial diagnosis and in patients with suspected local recurrence, can significantly alter the type of therapy given. Clinical studies using the (111)In radiolabeled immunoconjugate, MAb 7E11-C5.3-GYK-DTPA (capromab pendetide), have shown the superiority of radioimmunoscintigraphy over other diagnostic modalities in the detection of both primary and metastatic prostate cancer. Radioimmunoscintigraphy with capromab pendetide depends on expression of tumor-associated antigen rather than lesion size. Earlier detection of extraprostatic invasion and metastases by means of radioimmunoscintigraphy provides valuable information for treatment decisions. A case of metastatic prostate cancer in the abdomen of a patient without local disease, in which the extent of disease was confirmed at autopsy after sudden cardiac arrest, is presented.

Topics: Abdominal Neoplasms; Adenocarcinoma; Antibodies, Monoclonal; Humans; Indium Radioisotopes; Lymphatic Metastasis; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunodetection; Tomography, Emission-Computed, Single-Photon