Including Prostate Specific Antigen Research Articles

Safety and efficacy of the combination of high-dose calcitriol, docetaxel and aoledronic acid in hormone-refractory prostate cancer (HRPC): Interim report of a phase II trial

14600 Background: The purpose of this study is to assess the efficacy and safety of Calcitriol, Docetaxel and Zoledronic acid in patients with metastatic HRPC. The primary endpoint of the study is the toxicity profile. Secondary endpoints include prostate specific antigen PSA response and time to disease progression. Methods: 16 patients with HRPC were enrolled. All patients had confirmed diagnosis of prostate cancer and no previous cytotoxic therapy. All patients signed an informed consent. Patients received oral Calcitriol 0.5μg/kg on day 1 on weekly basis six out of eight-week cycles, Docetaxel 36mg/m2 on day 2 on weekly basis six out of eight-week cycles, and Zoledronic acid 4mg intravenously on weeks 1 and 5 of every 8-week cycle. Results: A total of 52 cycles were administered and toxicity was acceptable. No treatment-related mortality was encountered. No grade IV anemia, neutropenia, thrombocytopenia or diarrhea was reported. No grade IV gastrointestinal toxicities or thromboembolic events were reported. Grade IV infection was seen in 2 (3.8%) cycles (herpetic esophagitis and listeria meningitis). Grade III neutropenia was seen in 2 cycles (3.8%). Grade III diarrhea was seen in 1 cycle (1.9%) and grade II diarrhea in 4 cycles (7.7%). Grade II to III nausea and vomiting was reported in 8 cycles (15.4%). Grade II to III sensory neuropathy was noted after 17 cycles (32.7%). Grade III fatigue was reported in 5 cycles (9.6%). 14 patients were eligible for response analysis. Overall PSA response rate of our patients was 57.2%. Median time to disease progression was 6.5 months (range 2–15). One year survival was 57.1% (8 out of 14 patients). Conclusions: This interim analysis showed that the addition of Calcitriol to Docetaxel showed an acceptable safety profile as compared to Docetaxel regimens alone with less incidence of neutropenia and diarrhea. Previous studies using Docetaxel alone has reported higher incidence of neutropenia reaching 43–56% and grade III to IV diarrhea (10–34%). Our study suggests that Calcitriol might have a protective effect against the Docetaxel toxicities. No significant financial relationships to disclose.

Impact of Increased Number of Biopsies on the Nature of Prostate Cancer Identified

Increasing the number of cores obtained at the time of transrectal ultrasound guided prostate biopsy has increased the number of cancers identified. However, there is increasing recognition that many men with prostate cancer may not benefit from early, aggressive intervention and that over detection of prostate cancer has resulted in over treatment. We determined the impact of the greater number of prostate biopsies on the nature of cancer identified. In the Cancer of the Prostate Strategic Urologic Research Endeavor database, a longitudinal disease registry of men with prostate cancer, we identified those men diagnosed between 1999 and 2002 with complete data on serum prostate specific antigen, Gleason score, clinical T stage, number of biopsies obtained and number involved with cancer. We identified 4,072 men with 6 or more prostate biopsies obtained at initial diagnosis. Of the men 30%, 47% and 24% underwent 6, 7 to 11, and more than 12 biopsies, respectively. The number of biopsies correlated significantly with numerous sociodemographic and clinical variables including prostate specific antigen, comorbidities and income. There did not appear to be differences in disease characteristics as assessed by Kattan and Cancer of the Prostate Risk Assessment scores among men with a biopsy number between 6 and 17. In the subset of 1,548 men undergoing radical prostatectomy, no differences in biochemical-free survival were observed among the various biopsy groups at a median followup of 2.2 years. The increasing number of prostate biopsies obtained at diagnosis increases cancer detection but the impact on disease characteristics remains unclear. Our data suggest that the risk stratification of prostate cancers is independent of biopsy number (6 or greater) in a contemporary cohort of men.

The Prostate Cancer Prevention Trial: Design, Biases and Interpretation of Study Results

We describe the complexities of the study design of the PCPT and how they influenced the end point chosen, trial implementation, analysis and interpretation of the results. Data from the PCPT are provided to evaluate and quantify the potential biases of this trial design. Six potential sources of bias, including prostate specific antigen, digital rectal examination, prostate biopsy technique, study medication nonadherence and contamination, and transurethral prostate resection are presented. These biases resulted in the need for the end of study biopsy to evaluate the trial objectives. There were a large number of known and potential biases that worked for and against finasteride. Because of the trial design and inherent biases, it is imperative that interim biopsy results should be interpreted with caution. While the period prevalence end point that relied on an end of study biopsy was perhaps not the most clinically relevant, it was the only way to remove as much bias as possible and meet the study objective of determining if finasteride could decrease the risk of prostate cancer. The success of the PCPT depended on constant scrutiny by the Data and Safety Monitoring Committee to monitor these biases. The design and biopsy assumptions outlined at the inception of the trial were met, including adherence and contamination rates, the for-cause biopsy rate and the final percent of men with study end points.

Kallikrein-related peptidase (KLK) family mRNA variants and protein isoforms in hormone-related cancers: do they have a function?

The kallikrein-related peptidase (KLK) gene family of 15 serine proteases encodes many proteins, including prostate specific antigen (PSA or KLK3), that are well described and/or are potential biomarkers for hormone-related cancers. Variant mRNA transcripts produced by alternative splicing, polyadenylation or AUG sites, or intron retention have been found for each of the KLK genes. The predicted protein for many of these alternative transcripts is different from that of the classical kallikrein-related peptidases and would not be an active serine protease. The majority of these novel protein isoforms have not been studied in vivo. The possible function(s) of the variant transcripts/protein isoforms and potential roles that they may play in hormone-related cancers are still unknown and are the focus of this short review.

Weekly docetaxel as second line treatment after mitozantrone for androgen‐independent prostate cancer

Two recent phase III trials have shown an improvement in survival with the use of docetaxel in metastatic androgen-independent prostate cancer (AIPC) compared to mitozantrone. However no phase II trials have clearly defined the level of activity of docetaxel after mitozantrone. We sought to define the activity and toxicity of weekly docetaxel as second line chemotherapy after mitozantrone in men with AIPC. Twenty men were treated with docetaxel 40 mg/m2 weekly for 3 of every 4 weeks until progression or prohibitive toxicity. End-points included prostate specific antigen response, common toxicity criteria, time to progression and overall survival. Nine patients (45%) had a 50% or greater reduction in PSA maintained for at least 1 month. Weekly docetaxel was well tolerated with few major toxicities: two patients had Grade 3 diarrhoea (10%) and six had grade 2-4 haematologic toxicities (30%). The median time to progression was 5 months (range 0-13) and median survival was 13 months (range 1-24) from starting docetaxel. The median survival from starting mitozantrone was 19 months. Men who had responded to mitozantrone were no more likely to respond to docetaxel (P = 0.2 Fischer's exact test). Weekly docetaxel is a safe and active second-line treatment after mitozantrone for androgen-resistant prostate cancer, with similar levels of activity to the first-line setting.

Does the Prentice criterion validate surrogate endpoints?

Randomized Phase II or Phase III clinical trials that are powered based on clinical endpoints, such as survival time, may be prohibitively expensive, in terms of both the time required for their completion and the number of patients required. As such, surrogate endpoints, such as objective tumour response or markers including prostate specific antigen or CA-125, have gained widespread popularity in clinical trials. If an improvement in a surrogate endpoint does not itself confer patient benefit, then consideration must be given to the extent to which improvement in a surrogate endpoint implies improvement in the true clinical endpoint of interest. That this is not a trivial issue is demonstrated by the results of an NIH-sponsored trial of anti-arrhythmic drugs, in which the ability to correct an irregular heart beat not only did not correspond to a survival benefit but in fact led to excess mortality. One approach to the validation of surrogate endpoints involves ensuring that a valid between-group analysis of the surrogate endpoint constitutes also a valid analysis of the true clinical endpoint. The Prentice criterion is a set of conditions that essentially specify the conditional independence of the impact of treatment on the true endpoint, given the surrogate endpoint. It is shown that this criterion alone ensures that an observed effect of the treatment on the true endpoint implies a treatment effect also on the surrogate endpoint, but contrary to popular belief, it does not ensure the converse, specifically that the observation of a significant treatment effect on the surrogate endpoint can be used to infer a treatment effect on the true endpoint.

Seminal clotting and fibrinolytic balance: a possible physiological role in the male reproductive system.

Semen contains enzymes and inhibitors of the haemostatic system as well as the high molecular weight seminal vesicle (HMW-SV) proteins. The former may have roles in seminal clotting and in liquefaction through "fibrinolytic" activity, which may ultimately affect fertility. Although a limited number of studies have addressed the subject, the role of clotting and fibrinolytic factors in semen remains poorly understood. The liquefaction time and the distribution of components vary across split ejaculates. This may have an important bearing on the way clotting/fibrinolytic factors in semen are assessed. Semen contains tissue factor (TF, Thromboplastin, CD142), which originates from the prostate and is associated with prostasomes. The function of TF (and prostasomes) in semen is still a matter for speculation. Recently the presence of minute amounts of factor VII in semen has been demonstrated but its importance is uncertain. Semen also contains a thrombin-like enzyme, prothrombin fragments 1 and 2 (F1+2), D-dimer (DD) and thrombin-antithrombin (TAT) complexes. The presence of several fibrinolytic factors has been demonstrated in semen but few questions about their potential impact on semen quality have been raised. Factors found include tissue plasminogen activator (t-PA), urinary plasminogen activator (u-PA) and plasmin. There are also traces of fibrinogen, plasminogen, plasminogen activator inhibitor-1 (PAI-1), factor VIII coagulant activity (VIII:c) and fibrin monomers. The co-ordinate expression of both TF and PAI-1 by decidual cells of the endometrium is believed to be important in maintaining haemostasis during endovascular trophoblast invasion. Kallikrein-like serine protease inhibitors including prostate specific antigen (PSA) are known to be present in semen at high concentrations. In semen PSA is also found in a complex form with protein C inhibitor (PCI) with mutually inhibitory consequences. A better understanding of the spectrum of coagulating and liquefaction agents in semen to include classical haemostatic processes and the pathogenesis resulting from any imbalances between or within either system may provide the basis for the development of more selective and efficient agents affecting global fertility. Here we review aspects of male reproductive physiology in the light of recent findings concerning conventional clotting/fibrinolytic systems in human semen with a view to stimulating further research.

Laparoscopic Radical Prostatectomy: Decreasing the Learning Curve Using A Mentor Initiated Approach

Laparoscopic radical prostatectomy is being evaluated at several centers in the United States as a treatment option for localized prostate cancer. It is a technically difficult operation to perform with a steep learning curve. It has been stated that 50 procedures are necessary to satisfy the learning curve. To expedite performance and evaluation of laparoscopic radical prostatectomy a surgeon (mentor) who had performed 200 cases was invited to instruct a fellowship trained laparoscopist (trainee). From March 2001 through September 2001 we performed 30 laparoscopic radical prostatectomies. The mentor performed the first 12 procedures with the trainee acting as assistant (group 1). The subsequent 18 procedures were performed by the trainee with the mentor acting as assistant (group 2). A final set of 20 procedures was performed by the trainee alone using 1 of 3 urological residents as the assistant (group 3). The transperitoneal approach was used and all suturing was intracorporeal. Preoperative data included prostate specific antigen, clinical stage, Gleason grade and median patient age. Intraoperative data included operative time, the blood loss/transfusion rate and intraoperative complications. Postoperative data included pathological stage, prostate specific antigen, the positive margin rate, catheter dwell time and hospital stay. When applicable, statistical significance was determined using the standard paired t test. There was no statistical difference in median operative time in groups 1 and 2 (248 and 258 minutes, respectively, p = 0.15). Similarly there was no difference in groups 2 (trainee and mentor assistant) and 3 (trainee alone) (p = 0.26). There was a difference in operative time in groups 1 and 3 (p = 0.04). Mean estimated blood loss was comparable in groups 1 to 3 and not statistically different (150, 250 and 250 cc, respectively, p = 0.15). Mean organ weight was also comparable (64, 59 and 55 gm., respectively). Hospital stay was 3 days in all groups. Catheter time decreased as confidence was gained with the procedure (range 6 to 33 days). Final pathological stage was compared among the 3 groups. There was an overall increase in positive margins in groups 1 to 3 (16%, 22% and 30%, respectively, p not significant). However, the positive margin rate for stage pT2 disease was similar at 15.5% for groups 1 and 2, and 14% for group 3. Laparoscopic radical prostatectomy is a technically challenging operation that is in the early stages of evolution and evaluation. We present an intensive, mentor initiated approach to decrease the learning curve and maintain outcomes.

Metastasis Of An Ascending Colon Carcinoma In The Prostate 10 Years After Hemicolectomy

Secondary involvement of the prostate by malignant tumors is unusual unless direct invasion occurs. We report on a patient who presented with signs and symptoms of bladder outlet obstruction caused by a prostatic metastasis of an ascending colon carcinoma 10 years after hemicolectomy. CASE REPORT An 80-year-old man was admitted for transurethral prostatectomy because of repeat episodes of acute urinary retention. The patient had a history of partial resection of the ascending colon for adenocarcinoma (TNM pT3, grade 2, N0) 10 years prior to presentation, as well as resection of 2 solitary pulmonary metastases 7 and 5 years earlier. Routine laboratory tests were normal, including prostate specific antigen (1.04 ng./ml.). Only carcinoembryonic antigen was slightly increased (5.72 ng./ml.). Digital rectal examination revealed an increased consistency of the left lobe of the prostate. Colonoscopy, computerized tomography of the chest, abdomen and pelvis, and cerebral magnetic resonance imaging did not show local or distant tumor recurrence. Cystoscopy prior to transurethral prostatectomy demonstrated a normal bladder mucosa and 2 prominent lobes of the prostate. Transurethral prostatectomy was performed and the postoperative course was unremarkable. Histopathological evaluation of the entire surgical specimen revealed areas of benign micronodular prostatic hyperplasia, as well as small foci of a poorly differentiated cribriform and solid adenocarcinoma (fig. 1). The tumor cell cytoplasm was basophilic, and the grade of nuclear atypia and number of mitoses were remarkably high. Immunohistochemically, the tumor cells did not react with antibodies directed against prostate specific antigen or prostatic acid phosphatase. Cytokeratin 7 was also negative. However, the tumor cells stained positive for cytokeratin 20, a marker that is expressed in virtually all cases of colorectal carcinomas but is negative in prostatic carcinoma (fig. 2, a). In addition, carcinoembryonic antigen staining was positive, and p53 protein stabilization was detected in more than 90% of the tumor nuclei, a phenomenon typical for colorectal cancer but uncommon for prostate cancer (fig. 2, b). Therefore, the diagnosis of metastatic colorectal adenocarcinoma of the prostate was established. Because of age, radical prostatectomy was not considered despite the negative further metastatic workup. Instead, the patient was placed on external beam radiation therapy, which was ongoing at the time of this report.

Proteomic analysis of normal and malignant prostate tissue to identify novel proteins lost in cancer.

Alterations of important protein pathways, including loss of prostate secretory granules, and disruption of the prostatic secretory pathway have been identified as early events in malignancy. In this study, proteomics was used to map the differences in protein expression between normal and malignant prostate tissues and to identify and analyze differentially expressed proteins in human prostate tissue with particular regard to the proteins lost in malignancy. Small quantities of normal and malignant prostate tissue were taken fresh from 34 radical prostatectomy cases. After histological examination, proteins were solubilized from selected tissues and separated using two-dimensional electrophoresis. Using image analysis, the proteome of normal and malignant tissues were mapped and differentially expressed proteins (present in normal and absent in malignant tissue) were identified and subsequently analyzed using peptide mass finger printing and N-terminal sequencing. Western blotting and immunohistochemistry were performed to examine expression profiles and tissue localization of candidate proteins. Comparison of protein maps of normal and malignant prostate were used to identify 20 proteins which were lost in malignant transformation, including prostate specific antigen (PSA), alpha-1 antichymotrypsin (ACT), haptoglobin, and lactoylglutathione lyase. Three of the 20 had not previously been reported in human prostate tissue (Ubiquitin-like NEDD8, calponin, and a follistatin-related protein). Western blotting confirmed differences in the expression profiles of NEDD8 and calponin, and immunohistochemistry demonstrated differences in the cellular localization of these two proteins in normal and malignant prostate glands. The expression of NEDD8, calponin, and the follistatin-related protein in normal prostate tissues is a novel finding and the role of these important functional proteins in normal prostate and their loss or reduced expression in prostate malignancy warrants further investigations.

SYSTEMATIC TRANSPERINEAL ULTRASOUND GUIDED TEMPLATE BIOPSY OF THE PROSTATE IN PATIENTS AT HIGH RISK

A negative biopsy result does not necessarily equate with cancer in specific high risk groups. We describe an alternative systematic biopsy technique for evaluating this subgroup of patients. From March 1997 to May 1999 a total of 88 men underwent systematic ultrasound guided biopsy using the transperineal template technique. All patients had undergone at least 1 and 75 (85%) had undergone 2 or more previous sets of biopsies. In addition, study inclusion required high risk parameters, including prostate specific antigen (PSA) velocity greater than 0.75 ng./ml., PSA greater than 10 ng./ml. or previous prostatic intraepithelial neoplasia on biopsy, and/or atypical small cell acinar proliferation. Cancer was identified in 38 of the 88 men (43%) in this high risk subgroup undergoing repeat biopsy. A mean of 15.1 previous biopsy cores had been obtained. The most common biopsy grade was 6 (range 4 to 9). Adenocarcinoma was identified in the transition zone area in 29 of 38 cases (76%), including 15 (39%) in which disease was detected in the transition zone only. Persistent PSA acceleration greater than 0.75 ng./ml. was the major indicator for transperineal template biopsy in 83 of the 88 patients (94%). The only significant independent variable predictive of positive biopsy was prostate volume. Mean prostate volume in the positive and negative biopsy groups was 48 and 73 gm., respectively (p <0.001). Complications were rare and self-limiting, consisting primarily of hematuria and urinary retention requiring overnight catheterization in 2 patients. Systematic transperineal template biopsy of the prostate is a safe and precise repeat biopsy technique in patients who remain at high risk for adenocarcinoma.

MALIGNANT CYTOLOGICAL WASHINGS FROM PROSTATE SPECIMENS: : AN INDEPENDENT PREDICTOR OF BIOCHEMICAL PROGRESSION AFTER RADICAL PROSTATECTOMY

Malignant cells have previously been identified in the cytological washings of prostate specimens obtained at radical prostatectomy for clinically localized prostate cancer. We investigated whether malignant cells in the cytological washings of radical prostatectomy specimens predict biochemical progression. The affect of total androgen blockade on cytological washings was also examined. Cytological washings were obtained from radical prostatectomy specimens in 147 consecutive patients undergoing the procedure for clinically localized prostate cancer between November 1993 and April 1998. Of the 147 patients 54 were randomly selected to receive 1 month of total androgen blockade immediately before prostatectomy. To obtain the cytological specimen the extirpated prostate was subjected to a normal saline bath, as previously described. The cytology specimen was examined by a single cytopathologist blinded to preoperative and pathological findings. Biochemical progression, defined as prostate specific antigen 0.15 ng./ml. or greater, was determined using the Kaplan-Meier method. We also performed multivariate analysis of factors related to progression, including prostate specific antigen, pathological stage, margin status, Gleason grade and cytology status. Median followup was 37 months (range 13 to 66). Followup was available in 146 of 147 cases. Cytological washings were malignant in 14 of 92 patients (15%) who did not receive total androgen blockade preoperatively. In this group without androgen blockade the biochemical progression rate was significantly higher in those with positive cytology (p < 0.001). Positive cytology was an independent predictor of progression on multivariate analysis and a stronger predictor of progression than Gleason grade. No malignant cells were observed in cases of preoperative total androgen blockade (p < 0.001). However, biochemical progression was similar in the groups with and without androgen blockade (p = 0.355). Malignant cells may be identified in the cytological washings of radical prostatectomy specimens and they are an independent predictor of biochemical progression. One month of total androgen blockade preoperatively significantly decreases the rate of positive cytology but does not appear to change the rate of early biochemical failure.

Anti-proliferative effect of ginseng saponins on human prostate cancer cell line

Ginseng is a medicinal herb widely used in Asian countries, and many of its pharmacological actions are attributed to the ginsenosides. In a study of the anti-proliferative activity of ginsenosides using human prostate carcinoma LNCaP cell line, ginsenoside Rg3 displayed growth inhibitory activity. The cells lost its adherent property after incubation in the presence of 250 μM of ginsenoside for 48h. The expression of biomarker genes, including prostate specific antigen (PSA), androgen receptor (AR) and 5α–reductase (5αR), and that of the proliferating cell nuclear antigen (PCNA), were suppressed. Ginsenoside Rg3 induced classic apoptotic morphology and interfered with the expression of apoptosis-related genes, bcl-2 and caspase-3, in LNCaP cells, as demonstrated by fluorescence microscopy, flow cytometry and reverse transcriptase-polymerase chain reaction. Taken our results together, we suggested that ginsenoside Rg3 activated the expression of cyclin-kinase inhibitors, p21 and p27, arrested LNCaP cells at G1 phase, and subsequently inhibited cell growth through a caspase-3-mediated apoptosis mechanism.

PROSTATE REBIOPSY IS A POOR SURROGATE OF TREATMENT EFFICACY IN LOCALIZED PROSTATE CANCER

Purpose Many investigators use prostate rebiopsy as an indicator of treatment efficacy and tumor response of localized prostate cancer for therapies in which the gland remains in situ. Because of the inherent sampling error of needle directed biopsies, however, some men will have a false-negative rebiopsy even if they have had no therapy or if the therapeutic intervention was unsuccessful in eradicating the malignancy. We evaluate the risk of a false-negative biopsy and the clinical factors that influence this risk. Materials and Methods A total of 90 patients undergoing radical prostatectomy for clinically localized disease underwent sextant biopsy of the prostate immediately after removal of the gland. Data collected included prostate specific antigen (PSA), hormonal status, age and biopsy core status. Results Of the total study population 67.8% received neoadjuvant hormonal therapy. While all patients had pathologically confirmed adenocarcinoma within the prostatectomy specimen, 45.6% demonstrated a false-negative rebiopsy. Within a combined predictive model, PSA and hormonal status demonstrated a statistically significant effect on the false-negative rebiopsy rate. Predictive power of this combined model was high across the spectrum of risk for a false-negative rebiopsy. Conclusions This series demonstrates that the risk of a false-negative sextant biopsy in the presence of documented prostate cancer is high and is affected by several factors, including PSA and hormonal status. These data suggest that prostate sextant rebiopsy is an inaccurate method of assessing the therapeutic efficacy of treatments for carcinoma of the prostate in which the gland remains in situ following therapy.

The impact of the inclusion of endorectal coil magnetic resonance imaging in a multivariate analysis to predict clinically unsuspected extraprostatic cancer

The introduction of the endorectal coil magnetic resonance imaging (MRI) technique has improved the accuracy of preoperative staging for prostate cancer. This study quantifies the improvement in the ability to identify clinically unsuspected extraprostatic disease with the use of the endorectal coil MRI. A retrospective review of the pathologic findings of 347 patients with prostate cancer treated with a radical retropubic prostatectomy was performed. The preoperative clinical indicators including prostate specific antigen (PSA), clinical stage, Gleason score, and endorectal coil MRI data were employed in a multivariate analysis to identify patients who were at high risk for seminal vesicle invasion (SVI) or extracapsular extension (ECE). The sensitivity, specificity, and positive and negative predictive values for predicting SVI and ECE were calculated using the significant clinical indicators found on the multivariate analysis. The clinical factors identified on multivariate analysis as significant predictors of SVI include the endorectal coil MRI data (P < 0.0001), PSA (P = 0.0096), and the Gleason score (P = 0.012). Endorectal coil MRI data (P < 0.0001), PSA (P = .0001), and Gleason score (P < .0001) were significant predictors of ECE. In the patient subgroup with PSA (> 10-20 ng/ml) and Gleason score of 5 to 7, the addition of the endorectal coil MRI data enabled an additional 71 and 27% of patients with SVI and ECE, respectively, to be correctly identified. These patients would have been missed based on the prediction obtained from the PSA and Gleason score alone. The use of the endorectal coil magnetic resonance imaging data, in addition to prostate specific antigen and Gleason score, provides a more accurate prediction of the pathologic outcome of seminal vesicle invasion and extracapsular extension than the PSA and Gleason score alone for the patient subgroup with a PSA of greater than 10 to 20 ng/ml and Gleason score of 5 to 7.

Original Articles: Prostate Cancer: Detailed Preliminary Analysis of Iodine-125 Implantation for Localized Prostate Cancer Using Percutaneous Approach

Recent developments have permitted accurate seed placement and dosimetry for interstitial brachytherapy of selected patients with localized prostate cancer. We present our experience with 76 patients divided into 2 groups. Group 1 included 45 patients with smaller, more well differentiated tumors, usually less than 2 cm. in diameter on digital rectal examination or transrectal ultrasound and a Gleason score of less than 7 who were treated with 125iodine alone. Group 2 consisted of 31 patients with localized tumors greater than 2 cm. in diameter and/or a Gleason sum equal to or greater than 7 who were treated with low dose external beam radiation followed by 125iodine boost 4 weeks later. Complete clinical progression-free survival, including prostate specific antigen, digital rectal examination and biopsy, was 51% for group 1 and 63.3% for group 2, with a mean followup of 26.3 months. Prostate specific antigen progression-free survival was 97.7% for group 1 and 94.7% for group 2. These results appear to be superior to external beam radiation only although longer followup is needed to substantiate these favorable early results. The procedures were well tolerated with good potency sparing. They were performed on an outpatient or short stay basis and provided a good alternative to external beam radiation only or hormonal treatment for select patients with localized prostate cancer who may not be candidates for radical prostatectomy.

Original Articles

Recent developments have permitted accurate seed placement and dosimetry for interstitial brachytherapy of selected patients with localized prostate cancer. We present our experience with 76 patients divided into 2 groups. Group 1 included 45 patients with smaller, more well differentiated tumors, usually less than 2 cm. in diameter on digital rectal examination or transrectal ultrasound and a Gleason score of less than 7 who were treated with 125iodine alone. Group 2 consisted of 31 patients with localized tumors greater than 2 cm. in diameter and/or a Gleason sum equal to or greater than 7 who were treated with low dose external beam radiation followed by 125iodine boost 4 weeks later. Complete clinical progression-free survival, including prostate specific antigen, digital rectal examination and biopsy, was 51% for group 1 and 63.3% for group 2, with a mean followup of 26.3 months. Prostate specific antigen progression-free survival was 97.7% for group 1 and 94.7% for group 2. These results appear to be superior to external beam radiation only although longer followup is needed to substantiate these favorable early results. The procedures were well tolerated with good potency sparing. They were performed on an outpatient or short stay basis and provided a good alternative to external beam radiation only or hormonal treatment for select patients with localized prostate cancer who may not be candidates for radical prostatectomy.

Results of a randomized phase-III trial to evaluate the efficacy of strontium-89 adjuvant to local field external beam irradiation in the management of endocrine resistant metastatic prostate cancer

Purpose : A large proportion of the practice of radiotherapy in the management of metastatic adenocarcinoma of the prostate is associated with palliation of pain from osseous metastases and improving quality of life. Radiation therapy is well known to be effective in treating painful sites and may also be effective in reducing the propensity for adjuvantly treated disease to become symptomatic. Strontium-89 is a systemic radionuclide that has clinical efficacy in the palliation of pain from bony metastases. Methods and Materials : The study was a Phase-III randomized placebo control trial performed in eight Canadian Cancer Centers to evaluate the effectiveness of strontium-89 as an adjunct to local field radiotherapy. Patients with endocrine refractory metastatic prostate cancer received local field radiotherapy and either strontium-89 as a single injection of 10.8 mCi or placebo. Results : One hundred twenty-six patients were recruited. No significant differences in survival or in relief of pain at the index site where noted. Intake of analgesics over time demonstrated a significant reduction in the arm treated with strontium-89. Progression of pain as measured by sites of new pain or the requirement for radiotherapy showed statistically significant differences between the arms in favor of strontium-89. Tumor markers including prostate specific antigen, acid phosphatase, and alkaline phosphatase were also reduced in patients receiving strontium-89. A Quality-of-Life analysis was performed as a multivariate data set and demonstrated an overall superiority of strontium-89 with alleviation of pain and improvement in physical activity being statistically significant. Toxicity was evaluated and demonstrated increased hematological toxicity in the group receiving strontium-89. Conclusions : It is concluded that the addition of strontium-89 is an effective adjuvant therapy to local field radiotherapy reducing progression of disease as evidenced by new sites of pain and the requirement of further radiotherapy and improving quality-of-life and need for analgesic support in this group of patients.

A Screening Study of Prostate Cancer in High Risk Families

In a study of the familial risk of prostate cancer 17 sets of 2 brothers with prostate cancer were identified. A total of 34 first-degree relatives of these probands (sons and brothers, 55 to 80 years old) underwent an intensive screening examination that included prostate specific antigen, digital rectal examination, transrectal ultrasound and systematic as well as clinically directed core needle biopsies. Previously unsuspected and clinically relevant cancers were found in 8 men (24%), compared to the approximately 1 expected (p < 0.01). Of these cancers 2 were detected by the systematic biopsies. This study emphasizes the importance of thorough screening in first-degree relatives of prostate cancer patients.