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Currently there is no global agreement as to how extensively a radical prostatectomy specimen should be sectioned and histologically examined. We analyzed the ability of different methods of partial sampling in detecting positive margin (PM) and extraprostatic extension (EPE)-2 pathologic features of prostate cancer that are most easily missed by partial sampling of the prostate. Radical prostatectomy specimens from 617 patients treated with open radical prostatectomy between 1992 and 2011 were analyzed. Examination of the entirely submitted prostate detected only PM in 370 (60%), only EPE in 100 (16%), and both in 147 (24%) specimens. We determined whether these pathologic features would have been diagnosed had the examination of the specimen been limited only to alternate sections (method 1), alternate sections representing the posterior aspect of the gland in addition to one of the mid-anterior aspects (method 2), and every section representing the posterior aspect of the gland in addition to one of the mid-anterior aspects, supplemented by the remaining ipsilateral anterior sections if a sizeable tumor is seen (method 3). Methods 1 and 2 missed 13% and 21% of PMs and 28% and 47% of EPEs, respectively. Method 3 demonstrated better results missing only 5% of PMs and 7% of EPEs. Partial sampling techniques missed slightly more PMs and EPEs in patients with low-risk to intermediate-risk prostate cancer, although even in high-risk cases none of the methods detected all of the studied aggressive pathologic features.

Objectives: Routine placement of a pelvic drain may be avoided after total prostatectomy, traditionally known as "radical retropubic prostatectomy", with lymph node dissection (TP/LND). From our experience with 846 patients, we contend that patient safety and efficacy is not compromised by selectively omitting a pelvic drain., Materials and Methods: TP/LND was performed in 846 patients with clinically localized prostate adenocarcinoma. Patient demographics, clinical and pathological data were recorded and relevant data was analyzed. After the prostate was removed and the anastomotic sutures tied, saline was instilled into the bladder through the urethral catheter. If there was no significant leakage, hemostasis was adequate, and there was no injury to adjacent organs, a drain was omitted., Results: A drain was omitted in 624 (74%) of the 846 patients. The postoperative complication rates were compared between those with (D+) and without (D-) a drain. In the latter group, there were 24 (4%) immediate postoperative complications without a significant difference between the two groups (D+, 6%; D-, 4%; p = 0.25). When comparing the incidence of urinary retention, hematuria, anastomotic stricture, pelvic fluid collections, hematuria, and thrombolic events, there was no significant difference between patients with and without a drain., Conclusions: The morbidity of TP/LND is low when performed by an experienced surgeon. When the urethrovesical anastomosis is watertight and hemostasis is assured, a pelvic drain may be omitted without compromising patient safety and efficacy.

Purpose: Pre-prostate specific antigen era series demonstrated an increased risk of bladder cancer and rectal cancer in men who received radiotherapy for prostate cancer. We estimated the risk of secondary bladder cancer and rectal cancer after prostate radiotherapy using a contemporary population based cohort., Materials and Methods: We identified 243,082 men in the Surveillance, Epidemiology and End Results database who underwent radical prostatectomy or radiotherapy for prostate cancer between 1988 and 2003. We estimated the incidence rate, standardized incidence ratio and age adjusted incidence rate ratio of subsequent bladder cancer and rectal cancer associated with radical prostatectomy, external beam radiotherapy, brachytherapy, and a combination of external beam radiotherapy and brachytherapy., Results: The relative risk of bladder cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.88, 1.52 and 1.85, respectively. Compared to the general United States population the standardized incidence ratio for bladder cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.99, 1.42, 1.10 and 1.39, respectively. The relative risk of rectal cancer developing after external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy compared to radical prostatectomy was 1.26, 1.08 and 1.21, respectively. The standardized incidence ratio for rectal cancer developing after radical prostatectomy, external beam radiotherapy, brachytherapy and external beam radiotherapy-brachytherapy was 0.91, 0.99, 0.68 and 0.86, respectively., Conclusions: Men who receive radiotherapy for localized prostate cancer have an increased risk of bladder cancer compared to patients undergoing radical prostatectomy and compared to the general population. The risk of rectal cancer is increased in patients who receive external beam radiotherapy compared to radical prostatectomy. Patients should be counseled appropriately regarding these risks.

Objectives: The routine placement of a pelvic drain following radical retropubic prostatectomy (RRP) may not be required. We describe our experience in 552 consecutive RRPs to emphasise the safety of this approach and explain our rationale for avoiding a drain when possible., Methods: RRP was performed in 552 consecutive patients with clinically localised adenocarcinoma of the prostate between January 2002 and June 2005. Clinical and pathologic information was documented for each patient. After the prostate was removed and the anastomotic sutures tied, the bladder was gently filled with approximately 50 ml of saline through the urethral catheter. If there was no leak, a drain was not placed., Results: A drain was not placed in 419 (76%) of the 552 patients. We compared the postoperative complication rates in those with (D+) and without (D-) a drain. There were 27 (5%) immediate postoperative complications and no significant difference between the two groups (D+, 6%; D-, 5%; p=0.629): three (1%) patients who did not have a drain had a urinoma, one (1%) who had a drain had a lymphocele, and two (2%) who had a drain had a small pelvic haematoma., Conclusions: If the bladder neck is preserved or meticulously reconstructed, there may be little extravasation and, thus, routine drainage is unnecessary. Our 4-year experience indicates that morbidity is not increased by omitting a drain from the pelvic cavity after RRP in properly selected cases.

Purpose: We assessed biochemical and pathological factors as predictors of recurrence in men with seminal vesicle invasion., Materials and Methods: A consecutive series of 812 men who underwent radical retropubic prostatectomy between 1992 and 2000 included 106 (13%) with seminal vesicle invasion. Disease recurrence was defined as prostate specific antigen (PSA) 0.4 ng./ml. or greater. Patients with less than 12 months of followup, salvage radical retropubic prostatectomy, lymph node metastases and adjuvant therapy were excluded from study. Data on the remaining 66 cases were analyzed using the chi-square test, bivariate logistic regression, Kaplan-Meier analyses and Cox proportional regression. Variables included demographics, recurrence, time from surgery to recurrence, positive margins, capsular invasion, extracapsular extension, Gleason score (2 to 6, 7 and 8 to 10), and dichotomized values of preoperative PSA (10 or less versus 10 ng./ml.) and tumor volume (20% or less versus greater than 20%)., Results: Mean patient age was 62 years (range 48 to 74). At an average followup of 47.7 months (range 13 to 109) 53% of the patients were free of biochemical recurrence. Mean time to recurrence was 18.6 months (range 1.7 to 51.6). Univariate analyses revealed a statistical significant increased risk of recurrence in patients with PSA greater than 10 ng./ml. (p <0.0001), capsular invasion (p = 0.01) and age (p = 0.036). When adjusting for potential covariates, Cox proportional regression analysis indicated that higher PSA (hazard ratio 7.33, 95% CI 2.57 to 20.95), larger tumor volume (hazard ratio 5.64, 95% CI 1.97 to 16.19) and higher age (hazard ratio 1.13, 95% CI 1.04 to 1.22) were significantly associated with shorter time to recurrence., Conclusions: PSA greater than 10 ng./ml., tumor volume greater than 20% and age are significant predictors of recurrence after radical retropubic prostatectomy in patients with prostate cancer and seminal vesicle invasion. Hopefully future randomized trials may show a survival benefit of adjuvant therapy in patients at high risk.

Objectives: To correlate the extent and location of positive surgical margins after radical prostatectomy with disease progression., Methods: Data on 495 patients who underwent radical prostatectomy by one surgeon were analyzed. All radical prostatectomy specimens were sectioned entirely using 2 to 3-mm step sections by one pathologist. One hundred fifty-one patients (30.5%) had one or more positive surgical margins and were subjected to further detailed analysis. Recurrence was defined as a serum prostate-specific antigen (PSA) level of 0.2 ng/mL and rising on at least two postoperative measurements., Results: The mean follow-up was 25.3 months (range 3 to 73). The overall recurrence rate was 13.3%. Neoadjuvant hormonal treatment was given to 37 (25%) of those with a positive margin. Patients with positive surgical margins had a significantly higher incidence of recurrence compared with those with negative margins (27.8% versus 6.9%, P = 0.001). The recurrence rate for various locations was 29% apex/urethra, 30% posterior, 33% anterior, 36% lateral, 48% posterolateral, and 57% bladder neck. Time to recurrence was shorter in patients older than 70 years (P<0.055); with a preoperative PSA greater than 10 ng/mL (P<0.0001); with a biopsy Gleason score greater than 7 (P = 0.02); with a prostatectomy Gleason score greater than 7 (P<0.001); with seminal vesicle invasion (P = 0.0001); having more than 1 location of a positive margin (P = 0.002); or having a positive margin at the bladder neck (P = 0.0003) or the posterolateral surface of the prostate (P = 0.02) compared with other locations. Multivariate proportional hazards analyses indicated that age older than 70 (P = 0.005), a prostatectomy Gleason score of 7 (P = 0.015) or 8 to 10 (P = 0.003), and positive margin(s) at the bladder neck (P = 0.003) were independently associated with a shorter time to recurrence among patients with a positive margin., Conclusions: In our study, among patients with positive surgical margins, those with multiple positive margins, or a margin involving the bladder neck or the posterolateral surface of the specimen carried a higher risk of progression. A positive margin at the bladder neck appears to be the most significant adverse prognostic indicator. This information may help in decisions regarding additional therapy.

Background: Black race has been associated with a significantly increased risk of prostate cancer mortality. This exploratory analysis investigated the effect of race on the clinical outcome of combined androgen blockade (CAB)., Methods: Data for analysis were obtained from a double-blind, randomized, multicenter trial comparing CAB in the form of bicalutamide (50 mg once daily) or flutamide (250 mg three times daily) plus luteinizing hormone-releasing hormone analogs (LHRHa; goserelin acetate 3.6 mg, or leuprolide acetate 7.5 mg) in 813 patients with stage D(2) prostate cancer (median follow-up, 160 weeks). Patients were analyzed according to race (African American [AA], white, or other). The primary clinical events were disease progression and survival., Results: Four hundred and four patients received bicalutamide/LHRHa and 409 received flutamide/LHRHa. Although treatment with bicalutamide/LHRHa resulted in slightly longer time to progression and survival time in white and AA males than treatment with flutamide/LHRHa, the differences between the treatment groups were not statistically significant., Conclusions: No marked effect of race on clinical outcome was observed regardless of antiandrogen, suggesting that similar treatment benefits are to be expected in either race., (Copyright 1999 Wiley-Liss, Inc.)

Purpose: We determine the role of digital rectal examination in the followup of patients after radical prostatectomy., Materials and Methods: We retrospectively analyzed data on 501 consecutive patients who underwent radical retropubic prostatectomy between 1992 and 1998, and were followed at the University of Miami. Patients were evaluated at 3 to 6-month intervals after surgery with serum prostate specific antigen (PSA) and digital rectal examination. Biochemical recurrence was defined as PSA greater than 0.2 ng./ml. and increasing on at least 2 consecutive measurements. Local recurrence, detected by an abnormal digital rectal examination, was defined as an induration or nodularity in the prostatic fossa., Results: Mean followup plus or minus standard deviation was 25.4+/-20.8 months. Disease recurred in 72 patients (14.4%) and was biochemical in all. An abnormal digital rectal examination was noted in 4 patients, none of whom had an undetectable PSA at the time of a palpable abnormality., Conclusions: Our results suggest that an abnormal digital rectal examination after radical prostatectomy is always associated with a detectable PSA, which implies that performing a digital rectal examination in the absence of a detectable PSA may not be necessary.

Objectives: To assess whether age has an impact on biochemical recurrence after radical prostatectomy for localized adenocarcinoma of the prostate., Methods: Four hundred eighty-nine consecutive patients who underwent radical retropubic prostatectomy and did not have metastases to the lymph nodes were retrospectively analyzed. Disease recurrence was defined as a serum prostate-specific antigen greater than 0.2 ng/mL and rising on at least two postoperative measurements. Biochemical progression was compared in patients 70 years old or younger and older than age 70. The Kaplan-Meier estimator and Cox's proportional hazards model were employed to investigate the impact of age on time to recurrence. Neoadjuvant androgen deprivation was treated as a stratification variable in the Cox models., Results: The mean follow-up was 25.4 +/- 20.8 months. The Gleason score and extent of cancer in the pathologic analyses of the prostatectomy specimen was not significantly different between the two groups. Biochemical recurrence was detected in 12% of patients 70 years old or younger and in 25% of those older than 70 (P = 0.01). In multivariate analyses, after adjusting for all prognostic factors, younger age (70 years or younger) was independently associated with a longer time to recurrence (P <0.02)., Conclusions: Our results suggest that age per se may be an independent prognostic factor for disease recurrence after radical prostatectomy. This implies that patients 70 years old or younger are more likely to benefit from surgery. This information may be useful when counseling patients with clinically localized carcinoma of the prostate.

Background: A randomized, multicenter trial, double-blind for antiandrogen therapy, compared the antiandrogens bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue therapy (LHRH-A) in 813 patients with Stage D2 prostate carcinoma. An analysis of time to progression (median follow-up, 95 weeks) was performed to augment previous analyses of time to treatment failure and time to death., Methods: Patients were randomly assigned 1:1 to double-blind antiandrogen therapy, receiving either bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), and were assigned 2:1 to LHRH-A with goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). The primary endpoint of the trial was time to treatment failure, defined as an adverse event leading to withdrawal of randomized therapy, objective progression, death, or withdrawal from study therapy for any reason. Secondary endpoints were time to death, quality of life, and subjective response. The current analysis of time to progression included progression data collected prospectively for 561 patients (69%) and retrospectively for 252 patients (31%)., Results: Disease progression occurred for 223 of 404 patients (55%) in the bicalutamide plus LHRH-A group and for 235 of 409 patients (58%) in the flutamide plus LHRH-A group. The hazard ratio for time to progression of bicalutamide plus LHRH-A to that of flutamide plus LHRH-A was 0.9 (two-sided 95% confidence interval [CI], 0.75 to 1.08; P = 0.26). The upper one-sided 95% CI was 1.05, which met the definition of equivalence (< 1.25)., Conclusions: At a median follow-up time of 95 weeks, bicalutamide plus LHRH-A and flutamide plus LHRH-A had equivalent time to progression.

Thanks to earlier detection of clinically significant prostatic adenocarcinoma by measurement of serum prostate-specific antigen (PSA) levels, increasing numbers of patients are undergoing radical prostatectomy. However, the curative potential of this procedure is seriously limited by clinical understaging, which results in positive surgical margins and a marked increase in disease progression. In a multicenter study, histopathologic evaluation of radical prostatectomy specimens showed that presurgical androgen deprivation with leuprolide plus flutamide reduced the incidence of surgical margin involvement by 62%. In patients who received androgen deprivation therapy, characteristic and recognizable histopathologic changes in nontumor glands included atrophy, basal cell prominence, vacuolated luminal cell layers, and squamous and transitional cell metaplasia. Androgen deprivation markedly reduced the incidence of prostatic intraepithelial neoplasia (PIN) to 35%. The effects of androgen deprivation on prostatic carcinoma included smaller tumor glands, pyknosis and empty glandular spaces, and vacuolization and degeneration of tumor cells with an inflammatory response. Similar but less pronounced changes with no decrease in PIN were observed in finasteride-treated patients. It is important for pathologists to be aware of these histological changes and process tissue appropriately, because the changes affect the recognition and histological grading of tumors in radical prostatectomy specimens.

We report a primary squamous cell carcinoma of the prostate that developed in a 57-year-old man, 3 years after treatment with leuprolide and flutamide for Stage D1 adenocarcinoma of the prostate. This is the first case that describes this transformation from adenocarcinoma to squamous cell carcinoma following the use of luteinizing hormone agonists.

Prostate cancer has an unpredictable natural history if left untreated, particularly if the neoplasm is discovered when it is apparently organ confined. To our knowledge we report the first case of organ confined adenocarcinoma of the prostate in a cardiac transplant recipient. The therapeutic decision is complicated by the uncertainty of the impact of continued immunosuppression on tumor growth. Although the effect of immunosuppression on the growth of prostate cancer is unknown, our patient was treated within the accepted guidelines for similarly affected nonimmunosuppressed individuals. Improvements in long-term survival rates of patients undergoing cardiac transplantation warranted radical surgical ablation as treatment for this man with clinically organ confined prostate cancer.

When presented with a post-TURP patient with pathologically confirmed Stage T1a disease, several points should be considered (Fig. 1). Is the patient's anticipated longevity and quality-of-life likely to be affected by the confirmed diagnosis? From current knowledge, men over the age of seventy or with co-morbid risk factors probably will not be adversely affected, and no treatment is required apart from expectant follow-up with semiannual DRE and serum PSA determinations. The group at risk seems to be the young patient with a Stage T1a tumor who is likely to survive more than ten years after the diagnosis. Data showing progression rates without treatment as high as 16-25 percent at eight to ten years seem to indicate the need for additional therapy. If the patient belongs to this category and is ready to pursue more aggressive treatment, reestablishing the diagnosis might be suggested, as well as an evaluation of the pre- and post-TUR PSA levels. This can be done by TRUS-guided biopsies of the prostate (or repeat TURP, which we regard as less preferable). If residual tumor is not found, we would counsel a "wait and see" approach. If subsequent tissue sampling identifies other than well-differentiated cancer or indicates the likelihood of more extensive cancer than the T1a staging, treatment would be suggested. If the restaging reveals some residual well-differentiated disease that would not alter the initial staging of T1a, the patient should be offered the alternatives of close monitoring, radical prostatectomy, or radiation therapy. Until prognostic factors such as DNA ploidy and nuclear roundness are better studied, we are unable to counsel the patient on the biologic significance/aggressiveness of his Stage T1a disease.

Patients with Stage D2 prostate cancer relapsing on endocrine treatment have a grim prognosis. The role of a second-line hormonal treatment is debatable. We analyzed retrospectively, response and survival among 119 men (57 black, 62 white) progressing on a variety of first-line hormonal therapy. Sixty-one received a second-line hormonal treatment. Fifty-eight received only supportive therapy after first line therapy was discontinued. Age and race were not a factor in survival. Based on this retrospective study the optimal management for progressive metastatic prostate cancer cannot be delineated. However, the best results were in patients treated with diethylstilbestrol (DES) as a single treatment or when employed as either first or second treatment in patients receiving two therapies. The other modalities, e.g., bilateral orchiectomy, LH-RH analogues, and anti-androgens resulted in comparable outcomes when used either as single treatment or in combinations. Further clarification of the trends shown in this report require randomized controlled studies.

There are conflicting data on the effect of cigarette smoking on serum levels of the various sex hormones. Some studies suggest that cigarette smoke produces an antiestrogenic effect. Smoking may also affect the metabolism of other sex steroids such as testosterone and adrenal hormones, and thereby influence the incidence of benign and malignant growth of the prostate. Epidemiologic studies analyzing a possible association between cigarette smoking and prostate cancer are not conclusive, although some show a positive relationship. The etiology of BPH is undoubtedly multifactorial. Estrogens as well as androgens may be involved in the pathogenesis of BPH. There are several studies that indicate that cigarette smokers have a lower likelihood of requiring surgery for BPH. Growth of the prostate may not correlate with serum levels of androgens and estrogens. The local hormonal milieu of the target cells in the prostate are probably more critical than the more easily measured serum levels. This review examines the literature dealing with cigarette smoking and both BPH and prostate cancer. If there is an effect, then elucidation of the mechanism by which smoking affects the growth of the prostate may improve our understanding of BPH and prostate cancer, and may suggest preventive strategies for high risk groups.

One hundred eleven patients with endocrine-refractory Stage D prostate cancer were treated with weekly administration of 20 mg/m2 body surface area of doxorubicin hydrochloride (Adriamycin). Fifty-seven were part of a randomized study comparing doxorubicin and prednisone to prednisone alone. There were significantly more subjective responders in the doxorubicin group than in the prednisone group (p less than 0.01). The number of patients with evidence of stable disease was also higher during the chemotherapy arm compared with prednisone alone (p = 0.02). Patients taking doxorubicin had a slightly longer period of stable disease than did those taking prednisone (p = 0.08). Overall survival, however, was not prolonged (p = 0.26). Fifty-four patients took part in an open trial and 69 percent responded to treatment. All of these had clinical improvement. Side effects were minimal with cardiotoxicity noted in less than 15 percent among patients with side effects. Over 35 percent had no side effects. Thus single agent, weekly doxorubicin therapy as evaluated in our experience, while well tolerated and of subjective benefit, does not provide the patient with a significant longer progression-free survival or improved overall survival.

The resurgence of radical retropubic prostatectomy as a commonly employed treatment for organ-confined prostate cancer is largely a result of the reduction in morbidity related to the procedure. One aspect of this reduced morbidity is the potential to preserve potency. The technical points required to perform this procedure must be followed precisely or there is the potential for performing an inadequate cancer operation if these steps are not faithfully followed. We recently encountered a patient with local tumor recurrence because the initial urologist failed to adhere to these principles. A "salvage" procedure was performed.

We report preliminary results for the first 164 patients enrolled in a multicenter study comparing the endocrine effects, efficacy, and safety of 3.6 mg of goserelin acetate (Zoladex) and orchiectomy in patients with Stage D2 prostate cancer. Eighty-one patients were randomly allocated to receive Zoladex and 83 to orchiectomy. The median follow-up time for all patients was two hundred ten days. Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dL) within four weeks in both groups and remained suppressed for up to sixty weeks. An objective response according to modified criteria of the National Prostatic Cancer Project was observed in 81 percent and 78 percent of patients in the Zoladex and orchiectomy groups, respectively. There were no statistically significant differences between treatment groups in the distributions of time to treatment failure or time to disease progression. The most commonly reported adverse events in both treatment groups were hot flashes, cancer-related pain, unspecified pain, and urinary symptoms. These results suggest that Zoladex may offer an alternative to orchiectomy in the treatment of advanced prostate cancer.

Of 15 women with primary urethral carcinoma 2 had tumors confined to the urethra and were managed successfully by an operation. Of the 9 patients with tumor extending to the surrounding structures 6 (67 per cent) died of complications related to inadequate control of the primary tumor. The last 4 patients had stage D1 disease or greater at initial diagnosis and died of distant metastases. Our current approach for patients with locally advanced disease is combined brachytherapy and operation in an effort to eradicate the primary tumor, since morbidity and mortality result from failure to control the local tumor.

Transrectal ultrasound (TRUS) was used to predict tumor stage in 43 patients prior to radical prostatectomy. For assessing extracapsular extension, the sensitivity was 54 percent, specificity 58 percent, and accuracy 56 percent. For detecting seminal vesicle involvement, the sensitivity was 60 percent, specificity 89 percent, and accuracy 82 percent. The predominant tumor echo pattern was isoechoic in 37 percent of cases, mixed (hyper-, iso-, and hypoechoic) in 47 percent, and hypoechoic in 16 percent. An anterior-posterior to transverse dimension ratio of greater than 0.8 suggested diffuse involvement of the prostate with an increased chance of extracapsular spread.

Hydroxyproline is excreted in urine as a breakdown product of normal bone turnover: A dialyzable (D) fraction (90% of total) reflects active bone destruction and a nondialyzable (ND) fraction reflects bone growth/regrowth. In metastatic prostate cancer where blastic osseous metastases predominate, disease progression on bone scan correlated with elevation of both total hydroxyproline excretion (7.84 + 1.28, P less than 0.001) and the ND urinary level (0.94 +/- 0.20, P less than 0.01). In patients with a serially stable/improving scan, urinary excretion of each fraction (2.18 + 0.27 and 0.27 +/- 0.01) was similar to that of men with no evidence of disease. For Stage D2 prostate cancer, these two markers satisfactorily monitor osseous activity in the intervals between serial bone scintigraphy.

We have described a patient in whom complete regression of pulmonary metastases from renal cell carcinoma (RCC) followed treatment with medroxy-progesterone acetate (Depo-Provera). Although the reported rate of objective response to progesterone therapy in RCC is only 10% to 15%, the occasionally dramatic results, especially in men, warrant a trial of this agent. Other more toxic agents have consistently failed to provide significant responses.

Combination chemotherapy consisting of cyclophosphamide, doxorubicin hydrochloride and 5-fluorouracil was evaluated in 21 patients with metastatic adenocarcinoma of the prostate who were unresponsive to conventional therapy. All patients had extensive bone metastases. Of the 21 patients 5 (29 per cent) had a subjective response and an additional 12 (57 per cent) remained stable for 2 to 13 months after initiation of therapy. The median survival of patients with a subjective response was 60 weeks compared to 40 weeks for the stable patients. Patients who progressed on therapy had a median survival of 22 weeks. The significant response rate with a corresponding improvement in survival for patients on this 3-drug regimen suggests a need for additional trials to determine the response rate and survival compared to single agents.

At least 80 per cent of prostatic tumors exhibit some degree of hormone responsiveness. The preferred method of hormonal alteration has yet to be determined because new agents are currently undergoing clinical trials. The compounds tested have included cyproterone acetate, a progestational agent; flutamide, an antiandrogen that blocks the DHT-receptor complex in the tumor cell; and aminoglutethimide, which inhibits adrenal steroid production and, therefore, might further lower the level of circulating androgen following bilateral orchiectomy. The introduction of potent, synthetic analogues of gonadotropin-releasing hormone (GnRH) has provided another method of reducing the level of circulating androgen. A recent report on the efficacy of one of these analogues--leuprolide--in men with newly diagnosed metastatic prostatic cancer has revealed an initial response rate of 76 per cent (4% complete remissions, 32% partial remissions, and 40% stable) using National Prostatic Cancer Project criteria.

Sixty patients with prostatic carcinoma localized to the pelvis have been treated by external beam radiation therapy: 2 patients (2%) were Stage A, 12 (20%) Stage B, 14 (23%) Stage C, and 32 (53%) Stage D1. Twenty-two patients received adjuvant therapy (11 estramustine phosphate [Estracyt] and 11 cyclophosphamide [Cytoxan]) after radiation. Progression occurred in 22 patients (37%): 6 (10%) had local recurrence while 16 (27%) failed distally. The incidence of late major complications was 12 percent.

A case of osteogenic differentiation in a prostate gland associated with high-dose x-irradiation for adenocarcinoma is reported. Heterologous cancerous elements in adults are extremely unusual in the prostate and their occurrence after treatment has rarely been documented. The relationship of this lesion to the primary glandular neoplasm is discussed.

Carcinoma of the male urethra is infrequent. To date approximately 600 cases have been reported. We reviewed 16 cases of carcinoma of the male urethra seen at the University of Tennessee and the Memphis Veterans Administration Hospital. The mean patient age was sixty-three years (range 38 to 84). The most common presentation was a palpable mass followed by symptoms of urinary obstruction. Five urethral carcinomas arose distal to the suspensory ligament of the penis while 11 were of bulbar or bulbomembranous origin. The histology was squamous cell carcinoma in 8 patients (50%), mixed squamous and transitional cell carcinoma in 5 (31%), transitional cell carcinoma in 2 (13%), and adenocarcinoma in 1 (6%). The mean patient survival was fifteen months following diagnosis of a proximal urethral tumor and seventy-seven months for tumors arising distally. Neoplasms of the distal urethra can be surgically managed successfully even if regional lymph nodes are involved. The prognosis for proximal urethra tumors remains poor and is best treated by a combination of surgery and radiotherapy.

One hundred ten patients with metastatic prostate cancer (Stage D2) were analyzed to determine the associations among time until progression and the pretreatment testosterone level, extent of bone metastases as indicated by a semiquantitative grading scale for extent of disease, performance status, race, age, and the pretreatment level of prostatic acid phosphatase (PAP). The median follow-up period was twenty-one months, with a range of four to eighty-nine months. All patients received androgen deprivation at the time metastases were identified. A multivariate analysis demonstrated that pretreatment serum testosterone was the most significant variable associated with time until progression (P less than 0.01) and that the extent of bone metastases observed on the bone scan was the second most important variable (P less than 0.05). The following factors did not significantly correlate with progression-free intervals: age, race, and PAP. The performance status was significantly correlated, but was nonsignificant in the multivariate analysis when the model already included the testosterone level and the extent of bone metastases. Patients with a pretreatment testosterone level of less than 300 ng/dL and with more than six areas of increased uptake on the bone scan progressed more rapidly.

The best treatment for adenocarcinoma of the prostate depends on the patient's age, general medical condition, life expectancy, and willingness to accept such side effects as impotence. Radical prostatectomy or full-dose radiation therapy are usually curative when cancer is confined to the gland. The technique of prostatectomy has been improved and potency often can be preserved. Once the tumor extends beyond the gland, treatment alternatives are radiation or endocrine therapy. If lymph nodes are negative, radiation therapy may result in a long period without progression. If lymph nodes are positive, the expense and morbidity of radiation therapy may not be worthwhile because the likelihood of cure is low. Androgen deprivation, or endocrine manipulation, is preferred for metastatic disease. Response is varied and may depend on the patient's testosterone level when therapy is initiated. Survival is shorter in those with levels below normal.

An increasing incidence of bladder neoplasms temporally associated with chemotherapy, usually cyclophosphamide, is being reported. These secondary primary bladder malignancies are characteristically found in two groups of patients: those with lymphoproliferative or myeloproliferative tumors, and those with immunosuppression after organ transplantation. A case of adenocarcinoma of the bladder associated with malignant lymphoma is reported, and the known cases of second primary bladder malignancies after cyclophosphamide therapy as reported in the literature are reviewed. Studies relating to the enhanced occurrence of second primary cancers in lymphoproliferative disorders are presented. The recognized urologic toxicities of cyclophosphamide, including cytopathologic changes in animals and humans, are discussed. The observed association between immunosuppression and second primary malignancies is explored, as supported by studies on congenital immunodeficiency in humans, viral oncogenesis in experimental animals, and neoplasia after organ transplantation. Possible mechanisms of carcinogenesis associated with cyclophosphamide are reviewed, including suppression of humoral and cell-mediated immune defense mechanisms, direct carcinogenesis, or cocarcinogenesis. A plea is made for the orderly reporting and careful documentation of bladder tumors in patients receiving cyclophosphamide. It is suggested that prospective studies in these patients and in patients receiving cyclophosphamide for nonmalignant disorders would be of value in assessing the culpability of cyclophosphamide as a carcinogen.

The safety and efficacy of buserelin, a luteinizing hormone-releasing hormone (LH-RH) agonist, was tested in 33 evaluable patients with Stages C or D adenocarcinoma of the prostate. With a minimum follow-up duration of 10 months, there was one complete response and 22 partial responses (69%) by National Prostatic Cancer Project criteria, with a median duration greater than 18 months. Six patients (18%) had stable disease, median duration greater than 25 months, and only 12 patients have progressed. Performance status improved in 67%, patient-scored pain improved in 75%, and quality of life improved in 58%. Symptoms occurring during treatment consisted of hot flashes, loss of libido, and impotence. Buserelin produces a high frequency of durable objective and subjective responses in patients with advanced prostatic carcinoma.

Analysis of urinary hydroxyproline levels offers a marker to monitor osseous involvement in patients with metastatic malignancies. Such a marker is needed in patients with prostatic cancer when bone metastases predominate. Thirty-two men with stage D2 prostatic cancer were monitored by bone scan, acid and alkaline phosphatase values, and urinary hydroxyproline, beginning from 4 to 36 months after initiation of hormonal manipulation and/or systemic chemotherapy. In patients with disease progression determined by bone scan serial urinary hydroxyproline values progressively increased and were significantly elevated compared to urinary values obtained from patients with a stable or improving scan (p less than 0.001). Simultaneous alkaline phosphatase determinations showed less significant differences between patient groups. Acid phosphatase did not reliably indicate osseous response to therapy. These data suggest that urinary hydroxyproline values are predictive as an early objective sign of osseous response in patients receiving therapy for stage D2 prostatic cancer.