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S L Goldenberg

Publications and source records attributed to S L Goldenberg.

At least 19 recordsLinked to original sources
PubMed2001

Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects.

PURPOSE: A prospective phase 3 trial was initiated to determine whether 8 compared with 3-month neoadjuvant hormonal therapy reduces prostate specific antigen (PSA) recurrence rates after radical prostatectomy. Our interim analysis includes secondary end points of differences in biochemistry, pathology and adverse events between the 2 groups. MATERIALS AND METHODS: Men with clinically confined prostate cancer were randomized to receive 7.5 mg. leuprolide intramuscularly monthly and 250 mg. flutamide orally 3 times daily for 3 or 8 months before radical prostatectomy. Our study was powered to detect a 35% decrease in PSA recurrence, assuming a 30% recurrence rate in the 3-month arm after 3 years. RESULTS: A total of 547 men were randomized between August 1995 and April 1998. Men in the 8 and 3-month groups were equally stratified for T stage (29% T1c, 70% T2), Gleason grade (68% less than 4, 32% 4 or greater) and pretreatment PSA (63% less than 10, 27% 10 to 20 and 10% greater than 20 microg./l.). Mean pretreatment PSA was slightly higher in the 8-month compared with the 3-month group (11.64 versus 9.95 microg./l., respectively, p = 0.0539). A total of 44 men withdrew from study before surgery and, therefore, were nonevaluable. Preoperative PSA nadir was less than 0.1 microg./l. in 43.3% versus 75.1% (p <0.0001), and 0.3 microg./l. or greater in 21% versus 9.2% after 3 versus 8 months, respectively (p <0.0006). Mean serum PSA decreased 98% to 0.12 microg./l. after 3 months, with a further 57% to 0.052 microg./l. from 3 to 8 months. Transrectal ultrasound determined that prostatic volume decreased 37% from a mean of 40.6 to 25.4 cc after 3-month neoadjuvant hormonal therapy (p = 0.0001) and a further 13% to 22.2 cc after 8 months (p = 0.03). Mean hemoglobin decreased 15% (148.2 to 125.4 gm./dl.) after 3-month neoadjuvant hormonal therapy but stabilized thereafter. Radical prostatectomy was completed in 500 men, while surgery was aborted intraoperatively in 3. Positive margin rates were significantly lower in the 8 than 3-month group (12% versus 23%, respectively, p = 0.0106). There were no fatal adverse events and no differences between the 2 groups in the severity or causality (p = 0.287, 0.0564) of adverse events, or incidence of increased liver enzymes or diarrhea (p = 0.691, 0.288, respectively). However, men in the 8-month group noticed a higher number of newly reported adverse events (4.5 versus 2.9, p <0.0001) and higher incidence of hot flushes than the 3-month group (87% versus 72%, respectively, p <0.0001). CONCLUSIONS: Ongoing biochemical and pathological regression of prostate tumors occurs between 3 and 8 months of neoadjuvant hormonal therapy, suggesting that the optimal duration of neoadjuvant hormonal therapy is longer than 3 months. Longer followup is needed to determine whether longer therapy alters PSA recurrence rates.

Androgen Antagonists↗
PubMed2001

Rising prostate specific antigen after radical prostatectomy: a case based review.

Prostate specific antigen (PSA) has been proven to be a valuable tool in the diagnosis and staging of early prostate cancer and as a sensitive marker of residual or recurrent cancer after curative therapy. In 1998, 200 000 new cases of prostate cancer were reported in the SEER database. Two-thirds of these, or 134 000 men, underwent definitive therapy for localized cancer, including approximately 75 000 radical prostatectomies. It has been reported that 20%-50% of radical prostatectomy patients will have a PSA only recurrence. One can therefore estimate that every year 15 000 to 38 000 men will have a rising PSA following definitive surgical therapy. This elevation of PSA often precedes clinical failure by many years and poses a difficult management problem for which there are not, as yet, definitive management guidelines. This paper will review the definition of PSA recurrence, the natural history, diagnostic options and the therapeutic choices, as illustrated by several genuine cases.

Adenocarcinoma↗
PubMed2000

Long-term neoadjuvant hormone therapy prior to radical prostatectomy: evaluation of risk for biochemical recurrence at 5-year follow-up.

OBJECTIVES: To assess the effects of 8 months of neoadjuvant therapy on pathologic stage and biochemical recurrence rates. METHODS: One hundred fifty-six men with clinically localized prostate cancer were treated with neoadjuvant combined androgen withdrawal therapy for 8 months prior to radical prostatectomy. Preoperative clinical stage, Gleason score, and serum prostate-specific antigen (PSA) levels were compared with treatment outcome (pathologic stage and PSA recurrence). RESULTS: PSA at diagnosis was 10 microg/L or higher in 36% with a mean of 11.5 microg/L. Clinical stage was T1c in 18%, T2 in 74%, and T3a in 8%. Gleason score was 6 or lower in 76% and 7 or higher in 24%. Pathologic stage was T0 in 13%, T2 in 66%, T3 (specimen confined) in 13%, T3 (margin positive) in 6%, and TxN+ in 2%. Incidence of positive margins increased with clinical stage T3a versus organ-confined disease (25% versus 4%, P <0.05), pretreatment Gleason scores 7 or higher versus Gleason scores 6 or lower (11% versus 4%, P = NS), and pretreatment PSA levels higher than 10 microg/L compared with PSA levels lower than 10 microg/L (15% versus 0%, P <0.01). Overall PSA recurrence rate was 12.2% after a mean postoperative follow-up of 54 months. Risk of PSA recurrence increased with clinical stage (25% T3 versus 11% organ confined, P <0.01), pretreatment PSA (7% if PSA lower than 10 microg/L versus 21% if 10 microg/L or higher, P <0.02), Gleason score (9% if 6 or lower versus 22% if 7 or higher, P <0.02), and pathologic stage (6% of pT2, 24% of pT3M-, and 56% of pT3M+, P <0.01). PSA recurrences occurred in 6% of patients with no adverse preoperative risk factors, 12% with any one of the high-risk factors, and 29% with any two of the high-risk factors. CONCLUSIONS: Risk of PSA recurrence after 8 months of neoadjuvant therapy is low after 5 years of follow-up and remains proportional to the presence of adverse preoperative risk factors. Prospective randomized studies are required to determine whether longer duration of neoadjuvant therapy reduces the risk of biochemical recurrence after radical prostatectomy.

Adult↗
PubMed2000

Practice patterns of Canadian urologists in benign prostatic hyperplasia and prostate cancer. Canadian Prostate Health Council.

PURPOSE: We reviewed the practice patterns of Canadian urologists in benign prostatic hyperplasia (BPH) and prostate cancer, and assessed the changes that occurred between 1995 and 1998. MATERIALS AND METHODS: In 1995 and 1998 questionnaires were mailed to all active members of the Canadian Urological Association who practiced adult urology in Canada. Many questions were similar, allowing for the assessment of changes in practice patterns. RESULTS: A number of changes were observed between 1995 and 1998. Cystoscopy and imaging of the upper urinary tract were used less often to evaluate uncomplicated cases of BPH. However, 39% of respondents continued to perform cystoscopy routinely. Finasteride was no longer administered in men with a smaller prostate. In 1998 before radical prostatectomy 28% of respondents routinely performed a bone scan, 29% cystoscopy and 57% chest x-ray. The number believing that maximal androgen blockade is the most effective hormonal therapy decreased from 90% to 62%, while 24% reported in the 1998 survey that they frequently administered intermittent hormonal therapy. Comparison with an American study from 1995 indicated that American urologists used the American Urological Association symptom score and performed a prostate specific antigen test more frequently than Canadian urologists. However, Canadian urologists performed cystoscopy more frequently. CONCLUSIONS: These surveys provide a useful insight into the variations in clinical practice of Canadian urologists and help to determine whether changes are occurring in regard to the development of practice guidelines. They also indicate the need to develop further guidelines, and ensure that these guidelines are widely promoted and accepted by the urological community.

Adult↗
PubMed2000

Intermittent androgen suppression for prostate cancer: Canadian Prospective Trial and related observations.

The Canadian Prospective Trial of intermittent androgen suppression was a prototype therapeutic initiative started in 1995 for the management of patients in biochemical relapse after radiation for localized prostate cancer. An interim analysis has yielded several observations on the relations between baseline serum prostate specific antigen (PSA), nadir serum PSA, Gleason score, and time off-treatment. In a typical androgen-dependent tumor, the response of serum PSA to androgen withdrawal is biphasic, but with early tumor progression, plateauing of serum PSA is observed. Ligand-independent activation of the androgen receptor, a mechanism subserving the initiation of androgen independence, can be counteracted experimentally with decoy molecules and clinically with nonsteroidal antiandrogens. In some patients, it is possible to lengthen the off-treatment interval by inhibiting the enzyme 5 alpha-reductase, an effect that can be reinforced by lowering serum testosterone with an antigonadotropin. Serial measurements of serum PSA indicate that intermittent androgen suppression engenders a more diverse range of hormone-related responses than previously appreciated. These include: (1) repeated differentiation of tumor with recovery of apoptotic potential; (2) inhibition of tumor growth by rapid restoration of serum testosterone; and (3) restraint of tumor growth by subnormal levels of serum testosterone. These responses are aspects of regulation that should be taken into account when planning long-term treatment of prostate cancer with intermittent androgen suppression.

Androgen Antagonists↗
PubMed2000

Neoadjuvant hormone therapy: the Canadian trials.

The Canadian Urologic Oncology Group has carried out three studies of neoadjuvant hormonal therapy (NHT) in prostate cancer. The first, a study of 3 months of cyproterone acetate (CPA) 100 mg TID in patients undergoing external-beam radiation therapy, showed a benefit with respect to time to biochemical progression. There are no survival or clinical progression data available from this study. The second study involved 3 months of CPA prior to radical prostatectomy compared with radical prostatectomy alone and enrolled 200 patients. The probability of biochemical progression at 36 months was similar in the two groups (CPA 40%; surgery alone 30%; P = 0.3233). More recently, we have carried out a randomized trial of 3 v 8 months of leuprolide plus flutamide prior to radical prostatectomy in 547 patients. Patients were stratified by clinical stage, Gleason grade, and serum prostate specific antigen (PSA) concentration. In the 3- and 8-month groups, presurgery PSA concentrations were <0.1 ng/mL in 35% v 73%, and >0.3 ng/mL in 37% v 10%, respectively. In the 3- and 8-month groups, the positive margin rates were 17% and 5% and the organ-confined rates 71% and 91% (P < 0.01). One-year follow-up is now available on the entire cohort. Data regarding time to biochemical and clinical progression and overall and disease-specific survival will be required to determine whether this change in the pathologic findings translates into a patient benefit.

Androgen Antagonists↗
PubMed1999

CUOG randomized trial of neoadjuvant androgen ablation before radical prostatectomy: 36-month post-treatment PSA results. Canadian Urologic Oncology Group.

OBJECTIVES: To test the hypothesis that neoadjuvant androgen ablation before radical prostatectomy reduces the likelihood of biochemical progression at 36 months. METHODS: Two hundred thirteen patients with localized prostate cancer were randomized to radical prostatectomy alone (Sx, n = 101) or a 12-week course of 300 mg of cyproterone acetate daily followed by surgery (CPA, n = 112). Biochemical progression (two consecutive detectable prostate-specific antigen [PSA] values) was determined for the entire group and by baseline PSA, Gleason score, clinical stage, and pathologic stage. RESULTS: The probability of biochemical progression at 36 months was similar in both groups (CPA 40.2%, Sx 30.1%; P = 0.3233). CPA patients with baseline serum PSA between 25 and 50 ng/mL had a lower probability of biochemical progression (CPA 63.5%, Sx 84.6%; P = 0.0038). No difference in the probability of biochemical progression was seen between groups when analyzed by clinical stage or Gleason score. When analyzed by pathologic margin status, no difference was observed in the probability of biochemical progression in patients with organ-confined disease (P = 0.4484). There was a trend for a higher probability of progression in the neoadjuvant arm in patients with positive and negative surgical margins (P = 0.0105, P = 0.0459; alpha = 0.005 with Bonferroni adjustment). CONCLUSIONS: Neoadjuvant androgen ablation with CPA reduces the positive margin rate significantly but does not result in a difference in biochemical progression at 3 years. This may be due to a lack of sufficient follow-up, insufficient power of the trial to demonstrate a small benefit, or a true lack of benefit of neoadjuvant androgen ablation before radical prostatectomy.

Androgen Antagonists↗
PubMed1999

Impact of a shared decision-making program on patients with benign prostatic hyperplasia.

OBJECTIVES: To determine patient views about the Shared Decision-Making Program (SDP), an interactive videodisk program designed to inform patients with benign prostatic hyperplasia (BPH) about their condition and treatment options and to determine its impact on perceived knowledge and treatment preference. METHODS: Six hundred seventy-eight patients with symptomatic BPH from eight Canadian centers viewed the SDP. Before and after viewing the video, patients answered questionnaires designed to assess treatment preference, knowledge gained, and satisfaction with this educational format. A 1-year follow-up survey was also conducted. RESULTS: Most patients showed a high desire for information and high satisfaction with the SDP; this satisfaction persisted at 1 year. Patients' self-reported knowledge increased significantly (P <0.0001). However, the SDP did not alter initial treatment preferences among those with already formed preferences, although it aided almost half of those initially undecided in forming a preference. Viewing the SDP also appeared to enhance the physician-patient relationship. CONCLUSIONS: Patients saw the SDP as an effective method for teaching patients about BPH and the risks and benefits of various treatments, clarifying particular areas about which many patients appear to have a desire for more information than is often provided. Patients were enthusiastic about the educational value of the program, and their active participation in the decision-making process may actually enhance the physician-patient relationship. Contrary to other studies, we found no significant alterations in treatment preferences. Problems relating to the cost and timely updating of the software need to be addressed for these kinds of programs to realize their full potential.

Aged↗
PubMed1998

Prostate cancer: 6. Surgical treatment of localized disease.

A 65-year-old man undergoes a routine checkup before retiring. His wife has urged him to have his prostate examined, because she has read about testing for prostate cancer and a friend has just died of this disease. During the rectal examination, the man's physician discovers some firmness in the right lobe of the prostate gland. The patient has had no urinary symptoms and is in excellent general health. Sexual function is normal. There is no history of prostate cancer; his father died of a stroke at age 86 years. Testing shows that the patient's prostate-specific antigen level is 9.3 ng/mL, and he is referred to a urologist. Transrectal ultrasound-guided needle biopsy reveals adenocarcinoma with a Gleason score of 7 (intermediate grade). At a follow-up meeting with his physician, the patient says, "I have been doing some research, and it appears that I should have treatment. However, what is less clear to me is what form of therapy is best--surgery or radiation treatment. Please tell me what you can about the state of the art with respect to surgery."

Adenocarcinoma↗
PubMed1998

Transurethral electrovaporization of the prostate versus transurethral prostatic resection: a comparison of postoperative hemorrhage.

OBJECTIVES: To determine the acute and delayed hemorrhage rate of transurethral electrovaporization of the prostate (TEVP) versus standard transurethral resection of the prostate (TURP). METHODS: A retrospective review of 524 consecutive patients who underwent TURP and 302 consecutive patients who underwent TEVP was conducted. The indications for both procedures were identical and based on history, physical examination, American Urological Association symptom score, and uroflowmetry. Parameters of evaluation included the incidence of both initial and delayed hemorrhages, the time until a delayed bleed occurred, blood transfusion rates, and the average length of stay in hospital after a bleed. RESULTS: The overall hemorrhage rate for TURP and TEVP was 4.8% and 4.0%, respectively. In the TURP group, there was a 1.1% incidence of acute bleeds and 3.6% incidence of delayed bleeds. For the TEVP group, 0.3% had an acute hemorrhage, and 3.6% were readmitted for clot retention. The average length of time from original discharge to readmission was 12.9 days for the TURP group with a mean repeat stay of 5.7 days. For the TEVP group, the average interval to readmission was 15.4 days with a stay of 3.1 days. CONCLUSIONS: The overall rate of hemorrhage for the TEVP group was slightly lower than for the TURP group due to fewer acute bleeds. However, the incidence of delayed bleeds and clot retention between the two was identical at 3.6%. Because of improved hemostasis intraoperatively with similar functional results in the long term as shown by other investigators, we foresee TEVP continuing as a viable alternative to TURP.

Acute Disease↗
PubMed1998

Retroperitoneal lymphadenectomy for post-chemotherapy residual masses: is a modified dissection and resection of residual masses sufficient?

OBJECTIVE: To determine if post-chemotherapy retroperitoneal lymphadenectomy for residual masses can be limited to resection of the residual masses and a modified template dissection, without loss of therapeutic efficacy. PATIENTS AND METHODS: Between 1985 and 1995, 50 patients underwent one of three types of retroperitoneal lymphadenectomy for a residual mass after cisplatin-based chemotherapy for stages II and III testicular non-seminomatous germ cell tumour. The pre-operative imaging, operative record and pathology reports were reviewed to determine the location of the residual masses and whether tumour, defined as teratoma or viable carcinoma, was within the boundaries of the modified template and/or residual masses. The median (range) follow-up was 56 (1-140) months. RESULTS: Of 39 patients undergoing a bilateral dissection, one (2.6%) with a left testicular cancer had teratoma identified outside the boundaries of the modified template and the residual masses. The nine patients who underwent resection of residual masses and a modified-template dissection were relapse-free at a median follow-up of 55 months. One of two patients undergoing resection of residual mass alone had two recurrences arising from incomplete resection. Four of eight patients undergoing a modified dissection retained ejaculation, compared with seven of 25 (28%) undergoing a non-nerve sparing bilateral dissection. CONCLUSION: This retrospective study suggests that in patients whose tumour markers become normal and have a residual mass after chemotherapy, residual masses can be resected with a modified-template dissection with no significant risk of leaving tumour in the retroperitoneum.

Adolescent↗
PubMed1998

Delayed hypersensitivity and systemic arthralgia following transurethral collagen injection for stress urinary incontinence.

PURPOSE: During a prospective cohort study to determine the effectiveness of and adverse effects associated with transurethral collagen injection for treatment of stress urinary incontinence in women, we observed 3 cases of delayed allergic reaction at the skin test site associated with arthralgia. MATERIALS AND METHODS: A total of 337 women with at least a 1-year history, physical findings and urodynamic abnormalities consistent with stress urinary incontinence, who required pads or protective clothing and who had no or only grade 1 cystocele were enrolled in this prospective cohort study. Adverse effects were documented by a third party at each followup. RESULTS: Delayed reaction at the skin test site occurred in 3 patients (0.9%), and was associated with arthralgias in 2. CONCLUSIONS: The incidence and systemic nature of this type of reaction suggest that gluteraldehyde cross-linked collagen injection is not as innocuous as previously believed. Patients should be counseled regarding the unknown long-term outcome of this complication. Before treatment clinicians should consider double skin testing.

Adult↗
PubMed1998

Intermittent androgen suppression for prostate cancer: rationale and clinical experience.

The rationale behind intermittent androgen suppression (IAS) is based on: (1) observations that androgen ablation is palliative, not curative, in most patients with prostate cancer, and that quality of life must be considered; (2) the assumption that immediate androgen ablation is superior to delayed therapy in improving survival; (3) the hypothesis that if tumour cells surviving androgen withdrawal are forced into a normal pathway of differentiation by androgen replacement, then apoptotic potential might be restored and progression to androgen independence delayed. Several centres have now tested the feasibility of IAS therapy in non-randomized groups of prostate cancer patients using serum of prostate-specific antigen levels as trigger points. Clinical data suggest that prostate cancer is amenable to control by IAS and offers clinicians an opportunity to improve patients' quality of life by balancing the benefits of immediate androgen ablation (delayed progression and prolonged survival) while reducing treatment-related side effects and expense. Whether time to progression and survival is affected in a beneficial or adverse way is being studied in randomized, prospective protocols.

Androgen Antagonists↗
PubMed1998

Complications of periurethral collagen injection for stress urinary incontinence.

PURPOSE: Periurethral collagen injection has been advocated as a safe and effective method of treatment for stress urinary incontinence. This study was conducted to determine the complications associated with transurethral collagen injection for treatment of stress urinary incontinence in women. We report the incidence and management of adverse effects. MATERIALS AND METHODS: A total of 337 women with at least a 1-year history, physical findings and urodynamic abnormalities consistent with stress urinary incontinence, who required pads or protective clothing, and who had no or only grade 1 cystocele were enrolled in this prospective cohort study. A third party documented adverse effects at each followup. RESULTS: De novo urinary urgency with incontinence was the most frequent and serious complication, occurring in 12.6% of patients, and in many the symptoms were irreversible. Hematuria (5% of patients) and urinary retention (1.9%) were short-lived and resolved spontaneously. Delayed reaction at the skin test site occurred in 0.9% of the patients (3) and was associated with arthralgias in 2. CONCLUSIONS: Contrary to previous reports that periurethral collagen injection is complication-free, we found an overall incidence of 20% risk of complications in any given individual.

Biocompatible Materials↗
PubMed1998

Predictors of pathological stage before neoadjuvant androgen withdrawal therapy and radical prostatectomy. The Canadian Urologic Oncology Group.

PURPOSE: This prospective randomized trial was used to compare predictive factors for organ confined margin negative status after radical prostatectomy with and without a 3-month course of neoadjuvant androgen withdrawal therapy. MATERIALS AND METHODS: A total of 213 patients with localized adenocarcinoma of the prostate were randomized to radical prostatectomy with or without a 3-month course of 300 mg. neoadjuvant cyproterone acetate daily. Multivariate logistic regression analysis was used to determine significant predictors of organ confined margin negative status after radical prostatectomy in both groups. Parameters evaluated included baseline prostate specific antigen (PSA 4 or less, 4.1 to 10, greater than 10 ng./ml.), clinical stage (T2c versus T2b or less), biopsy Gleason score and percentage of surface area of biopsies involved with cancer. The multivariate analysis was repeated with PSA density and the natural logarithm of PSA to optimize the model. RESULTS: In the radical prostatectomy alone arm a model incorporating only PSA density was the best predictor of organ confined margin negative status. In the neoadjuvant androgen withdrawal therapy arm a model incorporating biopsy Gleason score, PSA density and clinical stage was the best predictor. CONCLUSIONS: The conventional predictors of pathology at radical prostatectomy, biopsy Gleason score, PSA density and clinical stage retain significance as predictors in patients treated with a 3-month course of neoadjuvant androgen withdrawal therapy before radical prostatectomy.

Adenocarcinoma↗
PubMed1997

Neoadjuvant androgen deprivation therapy before radical prostatectomy: who is unlikely to benefit?

OBJECTIVE: To determine which patients undergoing radical prostatectomy for localized cancer are unlikely to benefit from neoadjuvant androgen withdrawal therapy. PATIENTS AND METHODS: Over a 5-year period, 173 patients underwent radical retropubic prostatectomy: 87 patients received no pre-operative androgen withdrawal therapy, for whom the clinical stages were T1b (17 patients), T1c (3), T2a (31) and T2b/c (36). Pre-operative prostate biopsies contained well-differentiated cancer in 43 and moderately differentiated cancer in 44 patients. Serum prostate-specific antigen (PSA) ranged from 0.4 ng/mL to 110.1 ng/mL (median 5.0). The presence of extracapsular disease, positive surgical margins and seminal vesicle involvement were correlated with pre-operative PSA, PSA density (PSAD), the natural logarithm of PSA [In(PSA)], biopsy grade, clinical stage, and sparing of neurovascular bundles. RESULTS: Patients with a PSA < or = 4.0 ng/mL had a rate of extracapsular disease and positive margins of 8.3% and none had seminal vesicle invasion; corresponding rates for patients with a PSA > 4.0 ng/mL were 57%, 51% and 12%, respectively. Multivariate analysis revealed In(PSA) to be the best predictor of extracapsular disease (P < < 0.001), margin positivity (P < < 0.001) and seminal vesicle invasion (P = 0.0019). CONCLUSIONS: These results suggest that in patients who have clinically localized, well or moderately differentiated prostate cancer, a PSA < or = 4.0 ng/mL is predictive for organ-confined disease. This group is unlikely to benefit from neoadjuvant androgen deprivation. Ln(PSA) may be able to improve the accuracy of mathematical multivariate models predicting the presence of extracapsular disease or margin positivity, but this will require verification in larger population-based studies.

Aged↗
PubMed1997

Neoadjuvant androgen withdrawal therapy decreases local recurrence rates following tumor excision in the Shionogi tumor model.

PURPOSE: The role of neoadjuvant androgen withdrawal before radical prostatectomy continues to be defined and remains investigational. It is unknown whether decreases in positive margin rates will translate into lower biochemical and local recurrence rates until long-term followup is available. We determined whether local recurrence rates after tumor excision were less with neoadjuvant compared to adjuvant androgen ablation in the Shionogi tumor model. Androgen withdrawal in this model triggers apoptosis and complete tumor regression but rapidly growing androgen independent tumors inevitably recur after 1 month. Conceptually, the ideal time for excision is after maximal castration induced tumor involution but before outgrowth of androgen resistant clones. MATERIALS AND METHODS: Shionogi tumors were allowed to grow to 1 to 2 gm. before mice were randomly assigned to group 1-tumor excision with wide margins and castration at tumor recurrence and group 2-neoadjuvant castration for 10 days followed by wide excision of the regressed tumor. RESULTS: Tumors recurred locally in 87% of group 1 mice after a median of 17 days (range 6 to 24) and all regressed completely with adjuvant castration. However, androgen independent tumors recurred in 92% of mice after a median of 36 days. In group 2 androgen independent disease recurred in 44% of mice after a median of 40 days. Tumor-free survival was significantly greater in group 2 than in group 1 (56 versus 20%, respectively, p <0.05). Inked surgical resection margins were positive in two-thirds of group 1 and one-third of group 2 mice. CONCLUSIONS: Neoadjuvant androgen withdrawal decreases local recurrence and positive margin rates by 50% after tumor excision in the Shionogi tumor model. Although this model cannot address the issue of effect of neoadjuvant therapy on subclinical metastases, extrapolation of these results to the clinical disease suggests that neoadjuvant therapy may help to decrease not only the positive margin rates but also the subsequent risk of local recurrence following radical prostatectomy.

Animals↗