Rising Prostate-specific Antigen Level Research Articles

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.

Treatment of men with rising prostate-specific antigen levels following radical prostatectomy

Approximately one-third of patients who undergo radical prostatectomy for prostate cancer will develop a detectable prostate-specific antigen (PSA) level within 10 years. Biochemical recurrence of disease is defined as a rising PSA level in the absence of clinical or radiographic evidence of disease. Management of PSA recurrence is controversial, as prostate cancer may take an indolent course, or it may aggressively develop into metastatic disease. The only potentially curative treatment for biochemical failure after prostatectomy is salvage radiotherapy. Noncurative treatment options include hormone therapy or clinical trials of a novel systemic agent. This article will address management options for a rising PSA level after prostatectomy, as well as ongoing studies exploring molecular biomarkers as prognostic tumor markers and potential targets for prostate cancer therapy.

The Role of PCA3 Testing in Patients with a Raised Prostate-Specific Antigen Level After Greenlight Photoselective Vaporization of the Prostate

Greenlight(®) photoselective vaporization of the prostate (PVP) is an effective method for treating men with lower urinary tract symptoms. A rise in prostate specific antigen (PSA) levels, however, may be noticed in some patients during follow-up. The aim of this study was to determine whether the prostate cancer gene 3 (PCA3) urinary test would help identify patients who were in need of a prostate biopsy. The PSA of all patients undergoing PVP were analyzed. Patients with an elevated (above reference range) or rising PSA level (defined as > 0.75 ng/mL/year if the PSA was between 4.1 and 10 or a doubling time of less than 2 years) were offered a transrectal ultrasonography (TRUS) guided prostate biopsy. Before the biopsy procedure, all patients had a PCA3 test. The relationships between PSA, PCA3, and TRUS prostate biopsy findings were analyzed to determine sensitivity and specificity for the PCA3 test in this setting. 50 patients were identified. The mean age was 69.97 (range 57-83) years. The mean PSA level was 10.1 ng/mL (range 3.03-44.2 ng/mL). Six patients were found to have prostate cancer. Of those, five patients had a positive PCA3 test. One patient had a negative PCA3 test but positive biopsy findings. This gives a sensitivity of 83.3%, and a positive predictive value of 21.7%. The negative predictive value was 96%. The results suggest that a negative PCA3 test in our group of patients is a good predictor of negative biopsy results. The low positive predictive value may be an artefact of the group size. This will need further investigation and greater patient numbers to determine.

Phase II Study of the Human Anti-Epithelial Cell Adhesion Molecule Antibody Adecatumumab in Prostate Cancer Patients with Increasing Serum Levels of Prostate-Specific Antigen after Radical Prostatectomy

Background: Rising serum levels of prostate-specific antigen (PSA) after radical prostatectomy are indicative of recurrent prostate cancer. This double-blind, placebo-controlled phase II study evaluated the anti-tumour activity of the anti-epithelial cell adhesion molecule (EpCAM) antibody adecatumumab in delaying biochemical disease progression. Patients and Methods: Prostate cancer patients with increasing serum PSA levels following radical prostatectomy were randomized to low- (2 mg/kg) or high-dose adecatumumab (6 mg/kg) or placebo. The primary efficacy endpoint was the mean change from baseline in total serum PSA at week 24. Secondary endpoints included PSA response rate, prolongation of serum PSA doubling time and time to biochemical disease progression. Results: The primary and secondary endpoints of the study were not met in the predefined analyses. In a retrospective analysis of patients with baseline PSA ≤1 ng/ml and a high EpCAM expression, both the mean increase in PSA from baseline to week 24 and the PSA doubling time at week 15 were significantly improved in the high-dose adecatumumab group compared with the placebo group. Most frequent treatment-related clinical adverse events were gastrointestinal (diarrhoea and nausea) or general events (chills), showing a dose dependency but no grade 3/4 intensity in any patient. Conclusion: In men with rising PSA levels after radical prostatectomy and no evidence of clinical relapse, adecatumumab delayed disease progression in a subgroup of patients with baseline PSA levels ≤1 ng/ml and high EpCAM-expressing tumours.

Long-Term Follow-Up and Risk of Cancer Death After Radiation for Post-Prostatectomy Rising Prostate-Specific Antigen

The results of salvage radiation therapy for rising prostate-specific antigen (PSA) levels after radical prostatectomy appear favorable, but the ultimate outcome is uncertain, given the relatively short follow-up in most studies. We report on a group of patients at a median follow-up of 13.9 years after salvage radiation therapy. From 1990 to 1995, 92 patients were referred postoperatively for radiation for a rising PSA level. PSA level at the time of referral ranged from 0.1 to 30.5 ng/ml (median, 1.5 ng/ml). The median time from surgery to radiation was 2.1 years (range,, 0.3-7.4 years). Radiation was directed to the prostatic fossa only with a median dose of 6,500 cGy (range, 6,000-7,000 cGy). Eighty-five patients experienced a PSA drop after radiation, as predicted by Gleason score and PSA level at the start of radiation. Five- and 10-year biochemical failure free survival (BFFS) was 35% and 26%, respectively, and overall survival was 86% and 67%, respectively. Median survival was 12.0 years, and median BFF was 2.3 years. The presurgery PSA level was not predictive, but the PSA level at the start of radiation predicted a response. Patients with Gleason 8 to 9 cancers had a significantly higher progression rate than those with lower Gleason scores. There were no significant differences in outcomes based on pathology findings (none vs. positive margins vs. positive seminal vesicles). Overall, 22 (24%) patients died directly from prostate cancer, resulting in a 10-year cancer-specific survival rate of 82%. Multivariate analysis risk factors for dying of cancer were Gleason's score (8 to 9) and PSA at the start of radiation therapy (>1.0 ng/ml). Patients have a good response to salvage radiation therapy. A small but durable subgroup appears to have permanent control. In those for whom therapy fails, radiation delays the need for other salvage therapy, indicating at least a transient benefit to most patients.

1065 PREDICTORS OF ONCOLOGIC OUTCOMES AFTER SALVAGE RADICAL PROSTATECTOMY FOR RADIO-RECURRENT PROSTATE CANCER: A MULTI-INSTITUTIONAL COLLABORATION

1065 PREDICTORS OF ONCOLOGIC OUTCOMES AFTER SALVAGE RADICAL PROSTATECTOMY FOR RADIO-RECURRENT PROSTATE CANCER: A MULTI-INSTITUTIONAL COLLABORATION

Nanoparticle-based bio-barcode assay redefines “undetectable” PSA and biochemical recurrence after radical prostatectomy

We report the development of a previously undescribed gold nanoparticle bio-barcode assay probe for the detection of prostate specific antigen (PSA) at 330 fg/mL, automation of the assay, and the results of a clinical pilot study designed to assess the ability of the assay to detect PSA in the serum of 18 men who have undergone radical prostatectomy for prostate cancer. Due to a lack of sensitivity, available PSA immunoassays are often not capable of detecting PSA in the serum of men after radical prostatectomy. This new bio-barcode PSA assay is approximately 300 times more sensitive than commercial immunoassays. Significantly, with the barcode assay, every patient in this cohort had a measurable serum PSA level after radical prostatectomy. Patients were separated into categories based on PSA levels as a function of time. One group of patients showed low levels of PSA with no significant increase with time and did not recur. Others showed, at some point postprostatectomy, rising PSA levels. The majority recurred. Therefore, this new ultrasensitive assay points to significant possible outcomes: (i) The ability to tell patients, who have undetectable PSA levels with conventional assays, but detectable and nonrising levels with the barcode assay, that their cancer will not recur. (ii) The ability to assign recurrence earlier because of the ability to measure increasing levels of PSA before conventional tools can make such assignments. (iii) The ability to use PSA levels that are not detectable with conventional assays to follow the response of patients to adjuvant or salvage therapies.

An Open-Label, Single-Arm Phase Two Trial of Gefitinib in Patients With Advanced or Metastatic Castration-Resistant Prostate Cancer

To determine whether the oral epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa has clinical efficacy in patients with castration-resistant prostate cancer (CRPC). Multicenter open-label phase 2 study. Fifty-one male patients with CRPC and rising PSA levels were enrolled to obtain the target enrollment of 38 patients who completed at least 3 months of treatment with continuous gefitinib 500 mg/d. The primary end point was the prostate-specific antigen (PSA) response rate, as defined by a confirmed 50% decline in serum PSA. One patient had a confirmed PSA response, giving a response rate of 2.0% (95% CI 0.1-10.4%). The median time to progression was 28 days and the median time on study was 85 days. The majority of patients had a stable performance status while on study. Of the 51 patients who received at least 1 dose of gefitinib, 13 patients had a dose reduction and 9 patients withdrew because of an adverse event. There was minimal evidence of single-agent gefitinib activity in CRPC. The treatment was associated with clinically relevant toxicities, which responded to dose interruption or reduction.

Long-Term Clinical Outcome of Diagnostic Transurethral Resection of the Prostate in Patients with Elevated Prostate-Specific Antigen Level and Minor Lower Urinary Tract Symptoms

Introduction: In patients with minor lower urinary tract symptoms (LUTS), elevated prostate-specific antigen (PSA) levels and (multiple) negative multi-site biopsies, therapy decision is complex. Long-term outcome of a diagnostic transurethral resection of the prostate (TURP) in these patients needs to be determined. Methods: We retrospectively evaluated patients with minor LUTS, elevated PSA levels (≥4 ng/ml) and no signs of prostate cancer. Patients with bladder outlet obstruction (BOO) underwent TURP. When TURP showed no malignancy, patients were annually evaluated by PSA testing and the International Prostate Symptom Score (IPSS). Results: The study included 82 consecutive patients satisfying the inclusion criteria. All patients underwent TURP. No malignancy was encountered in 74 patients (90.2%). Of this group, 36 patients were followed >3 years (mean 62.1 months). One patient (2.8%) showed a persistently rising PSA level with positive extended multi-site biopsies 4 years after TURP, implying further treatment. 35 patients (97.2%) had a permanent complete normalization of PSA levels (<4 ng/ml) together with normalized IPSS. Conclusions: We consider an elevated PSA level in patients with minor LUTS and (multiple) negative multi-site biopsies as a sign of BOO. If these patients receive a diagnostic TURP, long-term outcome is excellent.

Oncologic outcome after radical prostatectomy in men with PSA values above 20 ng/ml: a monocentric experience

To assess the cancer control afforded by radical prostatectomy (RP) in patients with prostate-specific antigen (PSA) values above 20 ng/ml. We performed a retrospective review of prostate cancer patients who had initial PSA values above 20 ng/ml and were treated with surgery between 1995 and 2006. Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml after surgery. Overall, 41 patients were included. The mean age was 62 +/- 6.43 years. The mean PSA was 27.39 +/- 13.57 ng/ml (range 20.3-80). After pathological analysis, prostate cancer was organ-confined in 21 cases (51.2%) and locally advanced in 20 cases (48.8%). Positive surgical margins were detected in 36.5% of cases (n = 15). Five patients had lymph node involvement (12%). The mean prostate volume was 58 +/- 28.9 cc. The mean length of follow-up after surgery was 94 +/- 37 months. Median time to biochemical recurrence was 44.6 +/- 22 months. The 5-year PSA-free survival rate was 53%. Through univariate analysis, the pathologic stage (p = 0.016), biopsy and pathological Gleason scores (p = 0.013; p = 0.02) and positive margin (p = 0.04) were associated with recurrence. Overall, 24 patients (58.5%) experienced a biochemical recurrence. Only margin status and pathological Gleason were significant in multivariate analysis (p < 0.05). RP can be recommended as a viable primary treatment option in selected cases of the high-risk cohort of patients with pre-operative PSA values above 20 ng/ml. However, the modalities of adjuvant treatments following RP remain to be defined in patients who are likely to evolve unfavourably.

Salvage Radiotherapy for Rising Prostate-Specific Antigen Levels After Radical Prostatectomy for Prostate Cancer: Dose–Response Analysis

To investigate the association between external beam radiotherapy (EBRT) dose and biochemical failure (BcF) of prostate cancer in patients who received salvage prostate bed EBRT for a rising prostate-specific antigen (PSA) level after radical prostatectomy. We evaluated patients with a rising PSA level after prostatectomy who received salvage EBRT between July 1987 and October 2007. Patients receiving pre-EBRT androgen suppression were excluded. Cox proportional hazards models were used to investigate the association between EBRT dose and BcF. Dose was considered as a numeric variable and as a categoric variable (low, <64.8 Gy; moderate, 64.8-66.6 Gy; high, >66.6 Gy). A total of 364 men met study selection criteria and were followed up for a median of 6.0 years (range, 0.1-19.3 years). Median pre-EBRT PSA level was 0.6 ng/mL. The estimated cumulative rate of BcF at 5 years after EBRT was 50% overall and 57%, 46%, and 39% for the low-, moderate-, and high-dose groups, respectively. In multivariable analysis adjusting for potentially confounding variables, there was evidence of a linear trend between dose and BcF, with risk of BcF decreasing as dose increased (relative risk [RR], 0.77 [5.0-Gy increase]; p = 0.05). Compared with the low-dose group, there was evidence of a decreased risk of BcF for the high-dose group (RR, 0.60; p = 0.04), but no difference for the moderate-dose group (RR, 0.85; p = 0.41). Our results suggest a dose response for salvage EBRT. Doses higher than 66.6 Gy result in decreased risk of BcF.

Prostate‐specific antigen ‘bounce’ after permanent 125I‐implant brachytherapy in Japanese men: a multi‐institutional pooled analysis

To examine the incidence, timing, and magnitude of the prostate-specific antigen (PSA) level 'bounce' after permanent prostate brachytherapy (BT) and correlate the PSA bounce with clinical and dosimetric factors in Japanese patients with prostate cancer. A multi-institutional pooled analysis was carried out in 388 consecutive patients with T1-T2N0M0 prostate cancer treated with (125)I-seed implant BT with no hormonal therapy or external beam radiotherapy. All patients had >or=1 year of follow-up and at least three follow-up PSA level measurements. Three definitions of PSA bounce were used: definition A, a PSA level rise of 0.1 ng/mL; definition B, a PSA level rise of 0.4 ng/mL; and definition C, a PSA level rise of 35% over the previous value, followed by a subsequent fall. The actuarial likelihood of having PSA bounce at 24 months was 50.8% for definition A, 23.5% for definition B, and 19.4% for definition C. The median time to develop PSA bounce was 12 months for definition A, 18 months for definition B, and 18 months for definition C. There was a PSA bounce magnitude of 2 ng/mL in 5.3% of patients, and 95.3% of PSA bounce occurred within 24 months after (125)I-BT. Among the before and after (125)I-BT factors, clinical stage, initial PSA level, and Gleason score did not predict for PSA bounce using any definition; only being younger predicted for PSA bounce on multivariate analysis (P < 0.001). PSA bounce is a common phenomenon after (125)I-BT and occurred at a rate of 19-51% in the Japanese men who underwent (125)I-BT, depending on the definition used. It is more common in younger patients, and early PSA bounce should be considered when assessing a patient with a rising PSA level after (125)I-BT, before implementing salvage interventions. Furthermore, PSA bounce magnitude might be lower in Japanese than in Caucasian patients.

Tumor Amount in Prostatic Tissues in Relation to Patient Outcome and Management

The clinical significance of prostate cancer extent in prostatic tissue is dependent on the prostatic tissue sample type. For prostate needle core tissue and prostatic chips from transurethral resection of the prostate (TURP), the amount of cancer is of established clinical significance, whereas the intraglandular extent of cancer in radical prostatectomy tissues, although prognostic, is not routinely used for patient management. In the December 2008 and January 2009 issues of the Journal, Vollmer1,2 contributes important knowledge on the relationship of the amount of prostate cancer in needle core tissue1 and radical prostatectomy tissue2 with patient outcome. Prominent strengths of these investigations include the rigorous statistical analyses, the size of the characterized patient populations (>400 patients in each), and the facts that these were prospective studies and the clinical end point was overall survival. Prospective research studies reduce the capacity for selection bias that is a striking feature of retrospective studies. The pathology literature would benefit by inclusion of more studies that were designed as prospective. Commonly used end points in prostate cancer research studies are pathologic stage and Gleason grade and elevation of the serum prostate-specific antigen (PSA) level after treatment (so-called PSA or biochemical failure). However, PSA failure is a surrogate for survival, and not all men who experience a rising PSA level after treatment will have diminished life expectancy. Survival is often considered the “gold standard” end point for cancer treatment trials and should be the gold standard in characterization of the clinical significance of pathologic features in prostatic tissues, including tumor extent. Overall survival and cancer-specific survival have been used. Cancer-specific survival can be instructive in older patient groups that generally have a high incidence of comorbidities and intercurrent deaths. Few studies have linked tumor extent in prostatic tissue to overall survival …

Phase II trial of weekly docetaxel, zoledronic acid and selenium for hormone refractory prostate cancer

16113 Background: Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results especially when zoledronic acid was included. Moreover, preclinical and clinical trials showed that Selenium significantly reduced malignant prostate cell proliferation and the risk of developing prostate cancer. Methods: We conducted a phase II trial associating weekly Docetaxel, Zoledronic acid and Selenium. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, Docetaxel (25 mg/m2) on days 1, 8 and Selenium orally at 200 microg once daily for 21-day cycle. Results: Thirty one patients were selected but only twenty-seven were enrolled between August 2005 and November 2007. Median age was 67 years (range 53 to 83). A total of 135 cycles were administered with a median of 6 cycles per patient (2–6 cycles). The major toxicities were grades 1 to 2 anemia (37%), alopecia (7.4%) and motor neuropathy (7.4%). Out of the 27 patients assessed for efficacy, only 4 (15%) had a biologic response (>50% PSA decline). A total of 8 patients (30%) experienced clinical benefit with pain reduction. The median survival time was 15 months (95% CI: 11,19) whereas the median progression time was estimated at 6.5 months (95% CI: 5.0,8.1). Conclusions: Combination of weekly Docetaxel, Zoledronic acid and Selenium is a well tolerated regimen but but with limited efficacy. Adding Selenium to chemotherapy does not seem offering any therapeutic advantage. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis

Phase 2 study of granulocyte-macrophage colony-stimulating factor plus thalidomide in patients with hormone-naïve adenocarcinoma of the prostate

Objective To assess the efficacy of granulocyte macrophage colony-stimulating factor (GM-CSF) in combination with thalidomide on prostate-specific antigen (PSA) reduction in hormone-naïve prostate carcinoma (HNPC) patients with rising PSA levels after definitive local treatment. Materials and methods HNPC patients ( n = 21) with evidence of progression demonstrated by 3 consecutive rises in PSA and no evidence of radiographic involvement were treated on a chronic dosing schedule with GM-CSF. Patients received 250 μg/m 2 (maximum 500 μg) 3 times a wk by subcutaneous injection, with injections at least 24 h apart. Thalidomide administration began concurrently with an initial dose of 100 mg daily for 7 consecutive days. During wk 2 to 4, the dose was escalated every 7 d by 100 mg per individual tolerance to a maximum of 400 mg. The maximum tolerated dose of thalidomide was continued without interruption. PSA, testosterone, and routine laboratory parameters were measured every 6 wk. Results One patient was not evaluable because of noncompliance. For the 20 evaluable patients, baseline PSA levels ranged from 1.3 to 61.0 ng/ml. Nineteen patients left the study at 3.0 to 33.3 mo, secondary to individual tolerance, progressive disease, or development of a second primary tumor. One patient continues to receive therapy at 33.8 mo. Two patients did not respond to the therapy. For the 18 patients who did respond, the median reduction in PSA level was 59% (range 26%–89%), and the median duration of response was 11 mo (range 4.5–36). Grades 1–2 toxicity included peripheral neuropathy, fatigue, skin rash, and constipation. One patient had deep-vein thrombosis/pulmonary embolism. Conclusions GM-CSF plus thalidomide can be administered successfully with encouraging antitumor activity and reversible toxicity. This may represent an alternative to hormonal therapy.

Detection of prostate cancer in unselected young men: prospective cohort nested within a randomised controlled trial

Objective To investigate the feasibility of testing for prostate cancer and the prevalence and characteristics of the disease in unselected young men.Design Prospective cohort nested within a randomised controlled trial,...

Genetic changes in pT2 and pT3 prostate cancer detected by comparative genomic hybridization

Prostate-specific antigen (PSA) screening has led to a remarkable increase in prostate cancer cases undergoing operative therapy. Over half of patients with locally advanced cancer (>or=pT3) develop rising PSA levels (biochemical failure) within 10 years. It is very difficult to predict which patients will progress rapidly to advanced disease following biochemical failure (BF). Therefore, a more useful prognostic factor is needed to suggest the most appropriate therapies for each patient. To determine chromosomal aberrations, we examined 30 patients with stage pT2 or pT3 primary prostate adenocarcinomas and no metastases (pN0M0) by comparative genomic hybridization (CGH). Laser capture microdissection (LCM) was used to gather cancer cells from frozen prostate specimens. Common chromosomal alterations included losses on 2q23-24, 4q26-28, 6q14-22, 8p12-22 and 13q21-31, as well as gains on 1p32-36, 6p21 and 17q21-22. Losses at 8p12-22 and 13q21-31 were observed more frequently in pT3 than pT2 tumors (P<0.05 and P<0.01, respectively). Losses at 8p12-22 were more frequent in tumors with BF (P<0.05), and those at 13q12-21 were more frequent in tumors with Gleason score (GS) 7 or more than lower GS (P<0.05). These findings suggest that losses of 8p12-22 and 13q21-31 are important determinants of prostate cancer progression.

Lycopene and Soy Isoflavones in the Treatment of Prostate Cancer

Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen–independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.

Weekly docetaxel, zoledronic acid and estramustine in hormone-refractory prostate cancer (HRPC)

Treatment options for patients with hormone refractory prostate cancer (HRPC) showed unsatisfactory outcomes. Docetaxel-based combinations could offer more promising and tolerated results. A phase II trial was conducted with the combination of zoledronic acid, docetaxel and estramustine. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen levels (PSA) despite androgen deprivation therapy. Zoledronic acid was given at a dose of 4 mg on day 1, docetaxel (25 mg/m2) on days 1, 8 and 15, and estramustine orally at 140 mg two times daily on days 1 to 21 of a 28-day cycle. Twenty-seven patients were enrolled between October 2002 and November 2004. Median age was 68 years (53-83 years). A total of 124 cycles were administered with a median of 4.6 cycles per patient (1-8 cycles). The major toxicities were grades 1 to 3 anemia (55%), fatigue (15%), alopecia (11%) and hypocalcemia (11%). Two patients presented with deep venous thrombosis and died from pulmonary embolism. Another third patient died from Stevens-Johnson syndrome and grade 4 hepatic toxicity. Out of the 25 patients assessed for efficacy, 13 (52%) had a biologic response (>50% PSA decline). Three (21%) patients among the 14 with measurable disease had objective response: 1 complete response (CR) and 2 partial responses (PR). Response duration was 2 months for PR and 4 months for CR. A total of 12 patients (48%) experienced clinical benefit with pain reduction. This combination seemed effective; however toxic deaths especially from venous thrombosis counterbalanced the advantage of this regimen.

Adjuvant radiotherapy after radical prostatectomy

Abstract Background: Within 5 years following radical prostatectomy, between 15 and 60% of patients with pT3 prostate carcinomas show an increasing prostate specific antigen (PSA)as a sign of local and/or systemic tumour progression. Adjuvant radiotherapy (RT)for positive margins (R1)aims to reduce residual tumour cells in the prostatic bed, thus possibly reducing the biochemical progression rate. Apart from a large number of retrospective investigations, available results are presented from three randomised studies which have either been published completely (or in abstract form). Results: For pT3 prostate carcinomas, agreeing data are presented from three randomised studies, which show around a 20% reduced biochemical progression rate (bNED)after 4 to 5 years. With these data the results of numerous retrospective studies were conformed. The majority of the authors used total doses of 60 Gy. From one randomised study an increased local control rate was demonstrated as basis for the extended freedom of biochemical progression. The rate of acute and late side effects after three dimensional (3-D)planned radiotherapy with 60 Gy is very small and the rate of severe side effects is below 2%. The data situation for pT2 prostate carcinomas with positive margins is worse. Here, controversial data are presented, which require further investigation. Only retrospective data demonstrated a 25% advantage for adjuvant RT. Therefore, adjuvant radiotherapy also seems reasonable for pT-2 carcinomas with positive margins. Conclusions: The effectiveness of adjuvant radiotherapy for patients with pT-3 tumours with positive margins with and without undetectable PSA levels with 60 Gy total dose has been demonstrated. A survival advantage has not been shown until now. 3-D treatment planning remains the standard technique for these patients.For patients with positive margins in organ-limited prostate carcinomas (pT2 R 1)randomised studies are recommended.It remains unclear whether the adjuvant RT is superior to the radiotherapy for rising PSA levels out of the undetectable range after radical prostatectomy.