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Radical retropubic prostatectomy plus orchiectomy versus orchiectomy alone for pTxN+ prostate cancer: a matched comparison.

PURPOSE: Untreated stage pTxN+ prostate cancer is associated with a poor outcome. Monotherapy (surgery, radiation, hormonal therapy) alone is associated with a high progression rate. We evaluate whether radical prostatectomy and pelvic lymphadenectomy plus early adjuvant orchiectomy impart a survival advantage compared to pelvic lymphadenectomy and orchiectomy alone in a matched cohort of patients. MATERIALS AND METHODS: Between 1966 and 1995, 382 and 79 patients with stage pTxN+ prostate cancer underwent pelvic lymphadenectomy and radical prostatectomy plus early adjuvant orchiectomy (within 3 months of prostatectomy), and pelvic lymphadenectomy and orchiectomy only, respectively. We selected 79 matched controls from the prostatectomy plus orchiectomy group for the orchiectomy group. Patients were matched according to the number of positive nodes, clinical grade, clinical stage, age, year of surgery and preoperative prostate specific antigen (after 1987). The Kaplan-Meier method and stratified Cox proportional hazards model were used to estimate overall and cause specific survival for the 2 groups. RESULTS: There was an overall survival advantage at 10 years for the prostatectomy plus orchiectomy (66+/-6%) compared to the orchiectomy (28+/-6%) group (p <0.001, risk ratio 0.36, 95% confidence interval 0.20 to 0.66). There was also an advantage in cause specific survival at 10 years in the prostatectomy plus orchiectomy (79+/-5%) versus the orchiectomy (39+/-7%) group (p <0.001, relative risk 0.28, 95% confidence interval 0.13 to 0.59). After 1987, when matched on preoperative prostate specific antigen, the apparent survival advantage at 5 years with radical prostatectomy was smaller (79+/-8 versus 63+/-9% orchiectomy) and not significant (p = 0.19). CONCLUSIONS: This retrospective study of patients with stage pTxN+ PC suggests that radical prostatectomy with early adjuvant orchiectomy may provide a significant advantage in overall and cause specific survival compared to orchiectomy alone.

Aged↗

Orchiectomy and orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognosis: the final results of a European Organization for Research in Cancer Therapy Genitourinary Group Trial.

PURPOSE: The outcome of patients with symptomatic metastatic prostate cancer is poor and improved treatment regimens are urgently needed. Theoretically, the combination of orchiectomy and chemotherapy could reduce androgen sensitive and insensitive cells in the prostate. This European Organization for Research in Cancer Therapy Genitourinary Group randomized, multicenter phase III trial demonstrates the outcome of orchiectomy alone versus orchiectomy followed by intravenous mitomycin C. MATERIALS AND METHODS: A total of 189 patients with metastatic prostate cancer and poor prognostic factors were randomized in this trial by 42 institutions. Of these patients 184 (97%) were eligible for study, including 90 treated with orchiectomy alone (orchiectomy only arm) and 94 treated with orchiectomy followed by 15 mg./m.2 mitomycin C in 1 week (combined treatment arm). Mitomycin C was administered every 6 weeks and treatment was continued as long as tolerance and patient compliance allowed, and no progression was observed. Objective and subjective criteria for progression were clearly defined in the protocol. RESULTS: Patient and tumor characteristics were well balanced between the 2 treatment arms. At a median followup of 4.2 years 144 patients had died, including 112 of prostate cancer. No significant differences for time to overall (p = 0.17), subjective (p = 0.25) and objective (p = 0.08) progression were found between the 2 treatment groups. For progression-free survival no difference was noted (p = 0.67) between the 2 treatment groups but a trend in favor of orchiectomy alone was observed for overall survival (p = 0.04). Mitomycin C induced considerable hematological, gastrointestinal, renal and pulmonary toxicity leading to discontinuation in 31% of patients with pulmonary toxicity and 7% with renal deterioration. In addition, the quality of life evaluation revealed significant reduction in the combined treatment arm. CONCLUSIONS: Based on the results of this randomized phase III study orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognostic factors cannot be recommended due to failure of improvement in survival and reduced quality of life parameters.

Antibiotics, Antineoplastic↗

Experience in advanced prostatic cancer: orchiectomy and flutamide versus orchiectomy and estramustine phosphate.

OBJECTIVE: To compare pure hormonal treatment (orchiectomy plus flutamide) versus hormonal plus cytostatic treatment (orchiectomy plus estramustine phosphate [EMP]) as first-line therapy for advanced prostatic cancer. METHODS: From October 1985 to December 1991 a total of 99 patients were enrolled: 49 received orchiectomy plus EMP, 2 x 280 mg/day; 50 received orchiectomy plus flutamide, 3 x 250 mg/day. RESULTS: Of the 99 enrolled patients, 93 were evaluable for toxicity and 82 for efficacy. The median time to progression was 161 weeks for EMP versus 120 weeks for flutamide (p = 0.75, not significant). For distant metastases, bone pain, and poor performance status, treatment with EMP showed significantly better results than the flutamide group. The most frequent side effects were gastrointestinal for EMP and hot flushes for flutamide. CONCLUSIONS: For patients with advanced undifferentiated prostatic cancer and poor prognostic factors, treatment with EMP seems to show significant benefit.

Aged↗

Combined hormono/chemotherapy as primary treatment for metastatic prostate cancer: a randomized, multicenter study of orchiectomy alone versus orchiectomy plus estramustine phosphate. The Dutch Estracyt Study Group.

OBJECTIVES: Based on the theory that hormone-resistant cells are present in all metastatic patients, early administration of chemotherapy appears to be logical and its use is supported by experimental studies. Therefore, trials with combined hormonal and cytotoxic treatment as primary therapy should be conducted. In the present trial, the efficacy and tolerance of estramustine phosphate (EMP) as a chemotherapeutic agent in addition to hormonal treatment (orchiectomy) was studied in patients with metastatic and nonmetastatic prostate cancer not previously treated. EMP was chosen because it produces few serious adverse reactions and no cumulative toxicity. METHODS: Four hundred nineteen patients were included in a 1.5-year period starting in January 1989. Patients with locally advanced prostate cancer or with bone metastases were randomized to orchiectomy (O) or orchiectomy followed by EMP (O + E), given until progression. RESULTS: Analysis of the total group showed no significant difference in time to progression between the treatment groups. Because the course of the disease is different in patients with either T4 tumor only or with lymph node metastases only (M0) as compared with patients with bone metastases (M1) and because the number of progressions in the M0 patients was low, corresponding analyses were performed for these subgroups as well. In the M1 patients, there was a tendency for a longer time to progression in the O + E group than in the O group, but there was no indication of a difference between the groups with regard to survival. In the M0 patients, there was no indication of any difference in results between the treatments. Multivariate analysis of prognostic factors showed pain, alkaline phosphatase, metastasis status, and tumor stage to be significant factors. There was a relation between age and drug treatment in that a significant beneficial effect of EMP in terms of prolonged progression-free interval as well as survival was evident in younger patients (aged less than 73 years) with metastatic disease. Tumor stage was also of importance for the drug effect; T0 to T3 patients who received EMP survived longer than those who were treated with orchiectomy only. The most common adverse reaction was nausea in the O + E group, which led to discontinuation of the drug in 7 patients. Cardiovascular problems are not uncommon in this age group, and there was a higher incidence of cardiovascular events, predominantly cardiac failure, in the O + E group, leading to treatment interruption in 16 patients. CONCLUSIONS: Our results indicate that future studies of hormono/chemotherapy should focus on younger patients with bone metastases.

Aged↗

[Complete androgen blockade (orchiectomy + flutamide) versus androgen blockade with cytostasis (orchiectomy + estramustine) in the treatment of virginal advanced prostate cancer].

The results of orchiectomy + flutamide (n = 28) versus orchiectomy + estramustine (n = 27) in the initial therapy of advanced prostatic cancer were compared in a prospective randomized study. The minimum observation period was one year. In the group orchiectomy + flutamide the incidence of side effects was 25%, the response rate (complete + partial remission) was 28% and the progression rate was 18%. 5 patients (18%) died within the first year. In the group orchiectomy + estramustine the incidence of side effects was 22%, the response rate (complete + partial remission) was 29% and the progression rate was 33%. 2 patients (7%) died within 1 year of treatment. There is no significant difference either in the response rate or the progression rate between the two groups.

Aged↗

A comparison of diethylstilbestrol or orchiectomy with buserelin and with methotrexate plus diethylstilbestrol or orchiectomy in newly diagnosed patients with clinical stage D2 cancer of the prostate.

From April 1983 to March 1985, 265 patients with newly diagnosed metastatic prostate cancer were randomized to one of three treatment protocols: (1) diethylstilbestrol (DES) or bilateral orchiectomy, (2) the leutinizing hormone-releasing hormone (LHRH) analog buserelin, or (3) methotrexate plus DES or orchiectomy. In 261 evaluable patients there was no significant difference in survival between the three groups. However, progression-free survival (PFS) was significantly different (P less than 0.0005, log-rank test). Of the possible pairwise comparisons for PFS, two showed significance; buserelin was inferior to DES/orchiectomy (P less than 0.05) and buserelin was inferior to methotrexate plus DES/orchiectomy (P less than 0.0001).

Antineoplastic Combined Chemotherapy Protocols↗

Testicular function in patients with testicular cancer treated with orchiectomy alone or orchiectomy plus cisplatin-based chemotherapy.

Gonadal function was evaluated in 25 patients with metastatic testicular cancer who were treated with orchiectomy plus chemotherapy with cisplatin, vinblastine, and bleomycin (PVB) and in 21 patients with clinical stage I disease who were treated only with orchiectomy and then kept under surveillance. Four years after PVB treatment, none of the patients were azoospermic; after 5 years, the total sperm counts in 46% of the patients had reached their pretreatment levels. In the group under surveillance, sperm counts below the reference level persisted or developed in 55% of the patients. Sperm production was similar in the two groups of patients 1.5 years after treatment and beyond. We conclude that spermatogenesis is not restored in all patients treated with PVB because of both preexisting germ cell defects and treatment toxicity.

Adolescent↗

Hormonal effect of subcapsular orchiectomy versus total orchiectomy.

We conducted a controlled comparison to determine if subcapsular orchiectomy is as effective as conventional total orchiectomy in lowering serum testosterone in male rats. Both methods were effective. Our data refute earlier clinical reports and substantiate recent clinical studies.

Animals↗

Improved subjective responses to orchiectomy plus nilutamide (anandron) in comparison to orchiectomy plus placebo in metastatic prostate cancer. International Anandron Study Group.

Patients with advanced prostate cancer have a beneficial effect from maximal androgen blockade in terms of the subjective and objective delay of progression and median duration of survival, although side effects do occur more often in the combination treatment than in testicular suppression alone. Significant improvement or delayed deterioration in subjective parameters such as metastatic pain, performance status and urinary disorders strongly suggest (in the absence of validated questionnaires of quality of life at the time of this study) that orchiectomy plus nilutamide improves the quality of life as assessed by the subjective delay of progression, according to NPCP criteria, to an extent which outweighs the majority of adverse events.

Adult↗

[Therapy of metastatic prostatic cancer by orchiectomy plus Anandron versus orchiectomy plus placebo. Initial results of a randomized multicenter study].

In the course of a randomized double blind trial conducted by 7 Swiss urological centres, 51 patients with advanced, not pretreated carcinoma of the prostate were included. Following orchiectomy the patients were either administered 300 mg Anandron daily (Roussel RU 23908) or Placebo. Twelve months later the Anandron-group shows a slightly better objective response whereas there is no difference in survival rates. The adverse effects of Anandron-treatment are described.

Aged↗

Semen quality and reproductive hormones before and after orchiectomy in men with testicular cancer.

PURPOSE: We clarify the impact of removal of the tumor bearing testis on semen quality and reproductive hormones in men with testicular cancer. MATERIALS AND METHODS: Semen quality and levels of reproductive hormones were investigated in 48 men before and after orchiectomy for testicular cancer. Semen analysis was done in 35 of these men and hormone analyses were done in 47. The hormone data of patients with (14) or without (33) elevated values of human chorionic gonadotropin (HCG) were analyzed separately. RESULTS: Median sperm concentration and total sperm count decreased from 17 x 10(6)/ml. (range 0 to 117) and 39 x 10(6) (0 to 433), respectively, before to 7 x 10(6)/ml. (0 to 69) and 30 x 10(6) (0 to 200), respectively, after orchiectomy. After orchiectomy sperm concentration was decreased in 30 of 35 men (p = 0.001) and azoospermia developed in 3 (9%). In men without detectable HCG median follicle-stimulating hormone levels increased (p <0.001) from 5.7 IU/l. (range 0.01 to 30) before to 10.0 IU/l. (4.6 to 48) after orchiectomy in 33 of 33 patients. Median inhibin B significantly decreased (p = 0.003) from 108 pg./l. (range 60 to 193) before to 95 pg./l. (less than 20 to 141) after orchiectomy. Median luteinizing hormone increased significantly from 3.1 IU/l. (range 1.1 to 9.9) before to 5.2 IU/l. (2.1 to 27) after treatment (p <0.001). Testosterone and sex hormone-binding globulin did not change significantly after orchiectomy. Patients with detectable serum HCG before orchiectomy had a considerable increase in follicle-stimulating hormone after orchiectomy, and a concomitant decrease in testosterone and estradiol. CONCLUSIONS: Semen quality was poor at diagnosis and deteriorated further after orchiectomy compared with pretreatment values. Our findings indicate that in some patients the most appropriate time for cryopreservation of semen is before orchiectomy. Androgen production was maintained by increased luteinizing hormone stimulation after orchiectomy.

Adult↗

Pituitary function after orchiectomy in patients with or without earlier estrogen treatment for prostatic carcinoma.

Testosterone, FSH, LH and prolactin were measured before, and up to 36 months after orchiectomy in 62 patients with prostatic carcinoma; 36 were treated by primary orchiectomy, 10 by orchiectomy after prior estrogen treatment for less than 3 yr (short-term) and 16 for more than 3 yr (long-term). Before orchiectomy serum levels of testosterone, FSH and LH were significantly lower in estrogen-treated than in untreated patients. Following orchiectomy serum FSH and LH increased in all patients studied. However, long-term estrogen-treated patients had significantly lower FSH and LH both before orchiectomy and during the follow-up period than those treated by primary orchiectomy or orchiectomized after short-term estrogen treatment. In addition, in those long-term estrogen-treated patients, serum testosterone did not significantly decrease after orchiectomy, whereas in patients treated by primary orchiectomy or orchiectomized after short-term estrogen treatment serum testosterone fell significantly. At follow-up comparable levels of testosterone were found in the three patient groups studied. Prolactin levels did not differ significantly between the patient groups and were not elevated either before or after orchiectomy. It is suggested that patients with carcinoma of the prostate treated with estrogen for more than 3 yr have impaired, but slowly increasing, pituitary gland function, possibly caused by long-term effect of estrogen on the pituitary gland.

Aged↗

Orchiectomy during herniorrhaphy: what should we tell the patient?

Although orchiectomy is rarely required during inguinal herniorrhaphy, it is frequently a topic of preoperative concern. Our study disclosed a concomitant orchiectomy rate of 2 percent during 1,817 groin herniorrhaphies. The risk of orchiectomy was greatest in patients with incarceration (relative risk 22 times) but was also increased by herniorrhaphy for recurrence (relative risk 8 times) (Table II). On the other hand, patients undergoing repair of a primary reducible hernia were at low risk. Of the 29 patients undergoing orchiectomy, only 12 of the procedures were performed for specifically recorded testicular or spermatic cord abnormalities. The precise reason for orchiectomy was often not stated or was vague. We conclude that orchiectomy is more likely to be associated with repair of complicated hernias and that permission for possible orchiectomy should be obtained from these patients preoperatively. On the other hand, consent for orchiectomy and detailed discussion is unwarranted for patients with primary reducible hernias. In addition, orchiectomy during herniorrhaphy should be limited to cases of specific testicular and cord abnormalities, and the reason for orchiectomy should be clearly documented in the operative record.

Adult↗

Biphasic effect of orchiectomy on pro-opiomelanocortin gene expression in the hypothalamus.

Previous studies have shown that the hypothalamic concentration of pro-opiomelanocortin (POMC) mRNA and several POMC-derived peptides increases in the rat 4 weeks after orchiectomy and that this increase can be prevented by testosterone replacement. In this study, we have examined the short-term effects of orchiectomy on POMC gene expression in the medial basal hypothalamus (MBH). Adult male rats were studied at various time points between 1 day and 4 weeks after orchiectomy and compared to sham-orchiectomized rats. The MBH was homogenized and, after an aliquot was removed for beta-endorphin (beta-EP) radioimmunoassay, the RNA was isolated and the amount of POMC mRNA was measured using a solution hybridization S1 nuclease protection assay. In the first experiment, POMC mRNA was significantly higher 4 weeks after orchiectomy compared to that of the intact controls: 1.34 +/- 0.14 vs. 0.86 +/- 0.04 pg/micrograms RNA (p less than 0.01). Three days after orchiectomy, POMC mRNA was somewhat lower, 0.71 +/- 0.06 pg/micrograms RNA, but not significantly different from the controls. In a second experiment, POMC mRNA levels were measured 1, 2, 3, 4 and 7 days after orchiectomy. At 1 and 2 days after orchiectomy, POMC mRNA was lower than the controls: 0.51 +/- 0.02 and 0.52 +/- 0.06 vs. 0.70 +/- 0.09 pg/micrograms RNA. Levels then steadily increased to 0.61 +/- 0.04, 0.70 +/- 0.09 and 0.78 +/- 0.11 pg/micrograms RNA at 3, 4 and 7 days after orchiectomy, respectively. The mean level at 1-2 days after orchiectomy was significantly less than the controls (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗