Are bone scans necessary in men with low prostate specific antigen levels following localized therapy?

PURPOSE: The prostate specific antigen level at which to recommend a bone scan after treatment of early prostate cancer is controversial. We identified the incidence of bone metastases at varying prostate specific antigen levels in asymptomatic men following radical prostatectomy, radiation therapy and watchful waiting. MATERIALS AND METHODS: Data were obtained from the Early Prostate Cancer trial comparing placebo with bicalutamide in addition to standard care for localized prostate cancer. As part of the trial patients were required to have routine bone scans regardless of prostate specific antigen levels. The prostate specific antigen levels were divided into subgroups and the incidence of positive bone scans was calculated for each group. RESULTS: The incidence of positive bone scans in patients treated with watchful waiting and given bicalutamide or placebo was low (0.7% to 3.2%) at prostate specific antigen levels less than 20 ng/ml. At greater than this level the sample sizes were smaller but there was a significant increase in the incidence of positive bone scans. In the groups treated with radiation therapy or radical prostatectomy, regardless of the addition of bicalutamide, the incidence of positive bone scans was low (0.2% to 1.4%) at prostate specific antigen levels less than 5 ng/ml. The sample sizes were smaller at prostate specific antigen levels greater than 5 ng/ml so the results are harder to interpret. CONCLUSIONS: Bone scans can be confidently eliminated in the followup of patients with early prostate cancer after standard care of those with prostate specific antigen levels less than 5 ng/ml. This level can be increased to 20 ng/ml with caution in those patients treated with watchful waiting.

Watchful waiting for prostate cancer: a review article.

As earlier detection of prostate cancer increases because of prostate-specific antigen (PSA) testing, appropriate use for watchful waiting warrants re-evaluation. We have drawn together the significant watchful waiting literature and used it to evaluate the use of watchful waiting in the PSA era. We conducted literature searches for studies examining outcomes of watchful waiting and examined new literature emerging about the use of PSA for the follow-up of watchful waiting patients. Watchful waiting has the potential to play an increasingly important role in prostate cancer as less advanced disease is detected and methods are refined for identifying low-risk patients.

Can leakage at the vesico-urethral anastomosis be predicted after radical retropubic prostatectomy?

OBJECTIVES: To determine if low-risk patients can be identified in whom cystography is unnecessary to assess the integrity of the vesico-urethral anastomosis after radical retropubic prostatectomy (RRP), and thus who can have early catheter removal. PATIENTS AND METHODS: In all, 275 RRPs by one surgeon were analysed retrospectively; the surgical technique, blood loss and comorbidity were recorded. Cystograms were taken 8 days after RRP to assess vesico-urethral integrity before catheter removal. RESULTS: Of the 275 patients, 75% and 89% had cystography before 8 and 10 days after RRP, respectively; 71% of patients had no leak on cystography and were catheter-free at 8 days. Eighty-four leaks were identified, of which 25 (9.6%) were moderate or large. Previous transurethral prostatectomy, ischaemic heart disease, blood loss, mucosal eversion and preservation of the prostatic urethra were significant risk factors for developing a leak and were used to create a nomogram to assess the relative risk of leakage. However, none of the variables assessed, either alone or combined, could be used to predict which leaks were clinically significant. CONCLUSIONS: Leakage cannot be reliably predicted at the vesico-urethral anastomosis. Cystograms are necessary to identify clinically significant leaks at 8 days and should be taken if early catheter removal is being considered.

Current trends in the management of radical retropubic prostatectomy: is short-stay RRP feasible in the United Kingdom?

BACKGROUND: Our aim was to review UK practice in the management of radical retropubic prostatectomy and identify opportunities to reduce LOS to American levels. METHODS: A survey was conducted of BAUS members regarding LOS and postoperative management. RESULTS: Out of 551 surveys 126 were returned. Mean LOS in the UK is 5.2 days. Opiate analgesia, PCA and postoperative epidural may delay discharge. Diet and mobilization are commenced at 1.7 and 2.1 days, respectively. CONCLUSION: Care pathways can safely reduce LOS to 2 days. Protocols to reduce LOS in the UK should be assessed and their impact on cost and quality-of-life evaluated.

Will the experience with tamoxifen in breast cancer help define the role of antiandrogens in prostate cancer?

Breast and prostate cancers are the two predominant hormone-responsive tumours. The use of the antioestrogen tamoxifen in the treatment of breast cancer has evolved over the past 30 y from treatment for advanced breast cancer to prevention. Tamoxifen is currently the endocrine treatment of choice for advanced breast cancer and for adjuvant therapy in a broad spectrum of women whose primary tumours have functional oestrogen receptors. It has also been shown to reduce the incidence of breast cancer in high-risk women. Non-steroidal antiandrogen therapy is used in the treatment of prostate cancer, but its role is still being defined. The clinical development of tamoxifen and that of the antiandrogens are reviewed and parallels are uncovered which provide insight into contemporary and future management of hormone-responsive prostate cancer.Prostate Cancer and Prostatic Diseases (2001) 4, 72-80

Using outcome data and patient satisfaction surveys to develop policies regarding minimum length of hospitalization after radical prostatectomy.

OBJECTIVES: Changes in health care economics have prompted new clinical pathways for radical prostatectomy to reduce length of hospitalization after surgery to 1 day. We evaluated satisfaction, outcomes, and short-term morbidity in 187 consecutive patients with overnight hospitalization after radical retropubic prostatectomy (RRP). METHODS: In 1995, we initiated a critical pathway for RRP that included epidural anesthesia with or without spinal anesthesia and postoperative methadone, acetaminophen, and ibuprofen for pain control. Patients were discharged when they were afebrile, tolerating a regular diet, ambulating without assistance, and using oral medications for analgesia. An 18-item satisfaction survey was mailed to each patient 3 weeks after discharge. Responses to the postoperative survey, morbidity, blood loss, and use of transfusions were recorded. RESULTS: Of 252 patients who underwent RRP, 187 (74. 2%) were discharged 1 day after surgery. The mean age of patients was 61.4 years (range 42 to 73). A pelvic lymphadenectomy was performed in addition to the RRP in 32 men (17%). Epidural anesthesia with or without spinal anesthesia was used for all but 3 patients. The mean estimated blood loss was 1166 mL, and 24 patients (12.8%) required transfusion, with a mean of 1.9 U (range 1 to 6) of packed red blood cells. The postoperative complication rate was 11. 8%, of which 2.1% (n = 4) were definitely or probably related to our protocol. These complications included clot retention (n = 2), gastrointestinal bleeding (n = 1), and spinal headache (n = 1). Three of 187 patients were readmitted to the hospital within 30 days but only one (0.5%) required admission because of our protocol. The survey response rate was 91.4%. No patient was dissatisfied with his overall care, and only 10.5% of patients would have preferred to stay in the hospital longer. CONCLUSIONS: One-day hospitalization after RRP is associated with minimal postoperative morbidity and high patient satisfaction. Similar data are needed for RRP from other centers before policy decisions regarding the length of stay after this procedure are made.

Intention to be tested for prostate cancer risk among African-American men.

This study was conducted to identify factors associated with intention to be tested for prostate cancer risk among African-American men. Participants in this study included African-American men (n = 548) who were patients at the University Health Service at the University of Chicago, were 40 to 70 years of age, and did not have a personal history of prostate cancer. Baseline telephone survey data were collected for 413 (75%) men. Respondents were asked if they intended to have a blood test to assess prostate cancer risk. Univariate and multivariate analyses of intention to be tested for risk were performed. Eighty-six percent of the men said that they intended to be tested. Multivariate analysis results show that belief in the efficacy of prostate cancer screening [odds ratio (OR) = 3.6; 95% confidence interval (CI) = 1.4, 9.1] and intention to undergo a prostate cancer-screening (i.e., digital rectal examination and prostate-specific antigen testing; OR = 2.8; 95% CI = 1.3, 6.3) were positively associated with intention to be tested for prostate cancer risk. Being older (OR = 0.4; 95% CI = 0.2, 0.9), having had a prostate cancer-screening examination in the past year (OR = 0.5; 95% CI = 0.2, 1.0), perceiving one's prostate cancer susceptibility to be high (OR = 0.4; 95% CI = 0.2, 0.8), and being fatalistic about prostate cancer prevention (OR = 0.3; 95% CI = 0.2, 0.7) were negatively associated with intention to be tested for risk. Intention to be tested for prostate cancer risk was high among men in the study. Past screening, perceived susceptibility, and beliefs related to early detection might influence receptivity to genetic testing for prostate cancer risk.

Adherence by African American men to prostate cancer education and early detection.

BACKGROUND: This study was designed to identify factors that predict adherence by African American men to prostate cancer education and early detection. METHODS: In the spring of 1995, the authors identified 548 African American men who were patients at the University Health Services of the University of Chicago, were ages 40-70 years, and did not have a personal history of prostate cancer. Baseline telephone survey data were collected from 413 men (75%). Participants were randomly assigned to either a minimal or an enhanced intervention group. Men in the former group were mailed a letter and a reminder that invited them to a urology clinic for prostate cancer education and early detection. Men in the enhanced intervention group were sent the same correspondence and were also given print material and telephone contacts, which were tailored to each recipient. RESULTS: Adherence was significantly higher (OR = 2.6, CI: 1.7-3.9) in the enhanced intervention group than in the minimal intervention group (51% and 29%, respectively). Men who were age 50 years or older (OR = 1.7, CI: 1.1-2.8), were married (OR = 1.8, CI: 1.2-2.9), believed that prostate cancer early detection examination should be performed in the absence of symptoms (OR = 2.3, CI: 1.3-4.0), and self-reported an intention to have an early detection examination (OR = 1.9, CI: 1.2-2.9) were also more likely to adhere. CONCLUSIONS: A tailored behavioral intervention can influence adherence to prostate cancer early detection among African American men. Individual background and cognitive and psychosocial characteristics may also affect behavior. Future studies should assess the impact of this type of intervention on cognitive and psychologic correlates of decision-making and behavior along the continuum of prostate cancer care. [See editorial on pages 1-2, this issue.]

Endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of goserelin acetate administered every 13 weeks to patients with advanced prostate cancer.

OBJECTIVE: To determine the endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of Zoladextrade mark (goserelin acetate, Zeneca Pharmaceuticals, Wilmington, Delaware, USA), a luteinizing hormone-releasing hormone agonist analogue, when administration was extended from every 12 weeks to every 13 weeks in patients with advanced prostate cancer. PATIENTS AND METHODS: Between July 1995 and May 1996, 59 patients with either locally advanced (T3 or T4) or metastatic prostate cancer were enrolled in an open-label, multicentre trial. Primary efficacy endpoints were testosterone measurements, and assessments of prostate specific antigen (PSA) response, subjective and objective response. Quality of life (QoL) was a secondary efficacy endpoint. RESULTS: Mean testosterone concentrations decreased to < 0.3 microgram/L by week 4 and remained so for the duration of treatment. There were no statistically significant differences in mean testosterone levels between weeks 12 and 13, or weeks 25 and 26. Serum testosterone suppression was adequate in all 58 evaluable patients at week 13, and 51 of 52 (98%) patients at week 26. Of the 58 evaluable patients, 52 (90%) had a PSA response. A subjective response was recorded for six of 11 evaluable patients. Of 58 patients evaluable for objective response, 46 (79%) had a partial response, three (5%) had stable disease and nine (16%) had objective progression. Except for a significant (P=0.014) decrease in overall sexual interest, QoL was unchanged during therapy. The most common side-effects, regardless of causality, were hot flushes (67%), pain (31%) and pelvic pain (22%). Mild injection-site complaints occurred with only three of 221 (1.4%) depot injections. CONCLUSIONS: Zoladextrade mark 10.8-mg depot, administered every 13 weeks to patients with advanced prostatic cancer, is well tolerated, provides adequate suppression of serum testosterone and produces PSA, subjective and objective responses.

Improving knowledge about prostate cancer: the development of an educational program for African-Americans.

This study aimed to develop and test a prostate cancer educational program, as well as an electronic keypad survey procedure, among African-Americans. A 1 h seminar and 12-item knowledge questionnaire were reviewed by both professional and lay consultants and then tested among African-American men and women recruited from the city of Chicago. Eight free presentations were delivered to a total of 63 attendees. Mean percent correct rose from 20% pre-program to 57% post-program (P<0.001) and there was an increase on all individual questions. This feasibility study demonstrated: (a) there is a general lack of information about prostate cancer among African-Americans; (b) know-ledge can be significantly increased by means of an hour-long seminar; and (c) electronic keypads provide an easy, acceptable means of collecting data. Finally, the study underscored the need for the development of active and creative recruitment strategies to increase attendance. Such efforts are currently underway.

Overnight hospitalization after radical prostatectomy: the impact of two clinical pathways on patient satisfaction, length of hospitalization, and morbidity.

UNLABELLED: Changes in health care have prompted efforts to reduce length of hospitalization while maintaining quality care. Therefore, we evaluated short-term outcomes after radical retropubic prostatectomy on 100 consecutive men undergoing surgery for clinically localized prostate cancer performed under epidural anesthesia followed by epidural morphine or combined with spinal anesthesia using bupivacaine and fentanyl (25 micrograms) and followed by i.m. methadone (10-20 mg). All patients received oral acetaminophen and ibuprofen beginning 4 h after surgery. Length of hospital stay, responses to written satisfaction survey, postoperative morbidity and readmission to the hospital were recorded. Using either pathway, 83% of the patients were discharged after one night in the hospital. The mean hospital stay was 1.34 +/- 1.10 and 1.28 +/- 1.0 days, respectively. Although three men were rehospitalized, it was not because of the early discharge. More than 95% of patients were satisfied with pain control, and patients discharged after one night were not more likely to be dissatisfied than patients hospitalized longer. IMPLICATIONS: Both clinical pathways provide excellent anesthesia and analgesia and allow discharge 1 day after radical retropubic prostatectomy. Shortened hospital stay does not increase patient dissatisfaction or add to postoperative morbidity. Patients undergoing other pelvic and abdominal operations may also derive similar benefits using these pathways.

Comparison of goserelin and leuprolide in combined androgen blockade therapy.

OBJECTIVES: To perform exploratory analyses of data from a controlled trial that assessed the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with monthly depot preparations of leuprolide or goserelin, in patients with Stage D2 prostate cancer. One analysis compared goserelin plus antiandrogen therapy with leuprolide plus antiandrogen therapy; a second analysis compared the four combined androgen blockade (CAB) regimens. METHODS: This was a randomized, multicenter trial, open-label for luteinizing hormone releasing hormone analogue (LHRH-A) therapy, double-blind for antiandrogen therapy, with a two-by-two factorial design. Eight-hundred thirteen patients were allocated in a ratio of 2:1 to goserelin therapy (3.6 mg every 28 days) or leuprolide therapy (7.5 mg every 28 days) and 1:1 to bicalutamide therapy (50 mg once a day) or flutamide therapy (250 mg three times a day). The end points of time to progression and survival were assessed with a median of 160 weeks of follow-up. RESULTS: The percentages of progression events (70.9% versus 73.3%) and deaths (54.3% versus 56.8%) were similar for goserelin plus antiandrogen and leuprolide plus antiandrogen therapies. The hazard ratios for goserelin plus antiandrogen therapy to leuprolide plus antiandrogen therapy were 0.99 (95% confidence interval [CI] 0.84 to 1.18; P = 0.92) and 0.91 (95% CI 0.75 to 1.11; P = 0.34) for time to progression and survival, respectively. Goserelin plus antiandrogen and leuprolide plus antiandrogen therapies were generally well tolerated, and the side effects associated with depot administration occurred with a low frequency in the two groups. There were no significant differences among the goserelin plus bicalutamide, goserelin plus flutamide, or leuprolide plus bicalutamide therapy groups, but leuprolide plus flutamide therapy had a significantly poorer outcome than the other three therapies. The side-effect profiles for the four CAB groups were generally similar; diarrhea was more common among patients treated with flutamide and hematuria was more common among patients treated with bicalutamide. CONCLUSIONS: Although the results of these exploratory analyses should be interpreted with caution, they indicate that goserelin plus antiandrogen and leuprolide plus antiandrogen therapies are similarly well tolerated and have equivalent time to progression and survival, and that leuprolide plus flutamide therapy appears to be the least effective of the four CAB regimens.

Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms.

OBJECTIVES: To assess the effects of saw palmetto on voiding symptoms and urodynamic parameters in men with lower urinary tract symptoms (LUTS) presumed secondary to benign prostatic hyperplasia (BPH). METHODS: Fifty men with previously untreated LUTS and a minimum International Prostate Symptom Score (IPSS) of 10 or greater were treated with a commercially available form of saw palmetto (160 mg twice per day) for 6 months. The initial evaluation included measurement of peak urinary flow rate, postvoid residual urine volume, pressure-flow study, and serum prostate-specific antigen (PSA) level. Patients completed an IPSS, serum PSA was determined, and flow rate was measured every 2 months during the course of the study. A urodynamic evaluation was repeated at the completion of the 6-month trial. RESULTS: The mean IPSS (+/-SD) improved from 19.5+/-5.5 to 12.5+/-7.0 (P <0.001) among the 46 men who completed the study. Significant improvement in the symptom score was noted after treatment with saw palmetto for 2 months. An improvement in symptom score of 50% or greater after treatment with saw palmetto for 2, 4, and 6 months was noted in 21% (10 of 48), 30% (14 of 47), and 46% (21 of 46) of patients, respectively. There was no significant change in peak urinary flow rate, postvoid residual urine volume, or detrusor pressure at peak flow among patients completing the study. No significant change in mean serum PSA level was noted. CONCLUSIONS: Saw palmetto is a well-tolerated agent that may significantly improve lower urinary tract symptoms in men with BPH. However, we were unable to demonstrate any significant improvement in objective measures of bladder outlet obstruction. Placebo-controlled trials of saw palmetto are needed to evaluate the true effectiveness of this compound.

Evaluation of changes in prostate specific antigen in clinically localized prostate cancer managed without initial therapy.

PURPOSE: We define changes in prostate specific antigen (PSA) measurements with time in 49 men 71.9 +/- 7.0 years old (mean plus or minus standard deviation) with clinically localized prostate cancer who remain untreated. MATERIALS AND METHODS: We retrospectively analyzed PSA changes in prostate cancer patients managed by watchful waiting. In all patients a minimum of 3 PSA levels were measured at intervals of at least 6 months after malignancy was diagnosed. The rate of change in serum PSA level with time (PSA velocity) was determined using an exponential, log linear model. RESULTS: In 49 patients treated conservatively mean initial PSA level plus or minus standard deviation was 12.3 +/- 11.1 ng./ml. and mean PSA followup during which no therapy for prostate cancer was introduced was 32.1 +/- 13.2 months. PSA levels decreased during the observation period in 11 of the 49 patients (22%) and median PSA doubling time in the remaining 38 was 55.7 months (range 15.1 to 994.5). There was no significant correlation between age at diagnosis, Gleason sum, initial PSA level or clinical stage and PSA velocity. The short-term rate of change in PSA during the first 9 months after prostate cancer was diagnosed correlated poorly with overall PSA velocity. The short-term rate of PSA change was greater than the overall rate of change in 14 of 37 patients (38%). CONCLUSIONS: There is significant variability in the rate of change of PSA with time in men with clinically localized prostate cancer who remain untreated. The usefulness of serial PSA measurements in the management of watchful waiting is unclear. Changes in PSA may not be helpful or appropriate in determining the need for therapy after a period of observation.

Improved detection of recurrent bladder cancer using the Bard BTA stat Test.

OBJECTIVES: To evaluate the BTA stat Test in the detection of recurrent bladder cancer. METHODS: Sensitivity and specificity were determined using frozen voided urine samples from patients with recurrent bladder cancer, volunteers, patients with nonurologic conditions, and patients with a history of bladder cancer but free of disease. Results of cytology and the original BTA Test were compared with the sensitivity of the BTA stat Test in a large subgroup of the patients with cancer. RESULTS: The BTA stat Test detected 147 (67%) of 220 recurrent cancers. For those urine samples with previous cytologic and BTA Test results available, cytology had a sensitivity of 23%, the BTA Test 44%, and the BTA stat Test 58% for detection of recurrent cancer (P < 0.001, stat versus cytology). The specificity of the BTA stat Test was 72% for benign genitourinary disease and 95% in healthy volunteers. CONCLUSIONS: The BTA stat Test has high sensitivity and is significantly superior to voided urine cytologic analysis in the detection of recurrent bladder cancer.