Long-term autopsy findings following radical prostatectomy

In reviewing the Johns Hopkins Hospital records of over 1,000 radical prostatectomies performed since 1904, only 10 men have had a subsequent autopsy. All were managed by radical perineal prostatectomy without adjunctive therapy; 4 individuals had pathologic Stage B disease, and 6 men had pathologic Stage C cancer. The mean time interval between surgery and death was 8.9 years and 8.8 years for pathologic Stages B and C patients, respectively. Four patients (2 pathologic Stage B and 2 pathologic Stage C) had no evidence of disease, either local or distant, at autopsy. Two men (1 pathologic Stage B and 1 pathologic Stage C) had only microscopic foci of local recurrence without distant metastases. Four other patients (1 pathologic Stage B and 3 pathologic Stage C) had bulky distant metastases; of these, 1 had no local disease, and 3 patients had only microscopic recurrence in the pelvis. No patient had gross pelvic recurrence, and no individual with microscopic local disease had symptoms secondary to that recurrence. Four patients (1 pathologic Stage B and 3 pathologic Stage C) died of prostatic cancer secondary to distant metastases. These data suggest: radical prostatectomy alone provides excellent local control of the primary tumor, irrespective of the pathologic stage; in patients where bulky metastatic disease was responsible for death, distant dissemination may have occurred prior to radical prostatectomy since all patients had either no pelvic disease or only microscopic local recurrence.     

Treatment options for patients with stage D1 (T0-3,N1-2,M0) adenocarcinoma of prostate

Three hundred six patients with adenocarcinoma of the prostate underwent pelvic lymphadenectomy and had Stage D1 (T0-3,N1-2,M0) disease; 171 patients underwent radical retropubic prostatectomy with or without immediate adjuvant therapy (hormonal or radiation or both) or conservative (hormonal or radiation or both) treatment alone (n = 135). Follow-up was one-half to eighteen and one-half years (mean, 5 yrs). Immediate adjuvant orchiectomy significantly (P = 0.01) improved survival (87.4% at 10 years) and nonprogression rates for patients who underwent radical prostatectomy, but not for those who had lymphadenectomy. Overall patient survival was significantly better (P = 0.005) after prostatectomy than lymphadenectomy. Residual disease (n = 43) in patients who underwent prostatectomy and received adjuvant treatment (orchiectomy or radiation or both) did not affect disease outcome. Bilateral pelvic lymphadenectomy and radical prostatectomy with immediate adjuvant orchiectomy provided survival comparable to the expected survival; conservative treatment alone was associated with rapid disease progression and poor survival and significantly (P = 0.02) higher local morbidity.     

Perioperative complications of pelvic lymphadenectomy and radical retropubic prostatectomy for Stages C and D1 prostate cancer

The complications experienced by 205 consecutive patients who underwent bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for surgical Stages C and D1 prostate cancer were analyzed. One hundred five patients had pathologic Stage C disease, and 100 patients had pathologic Stage D1 disease. Seven patients had thromboembolic complications. Wound or pelvic hematomas developed in 6 patients. Only two lymphoceles were detected. Rectal injuries occurred in 6 patients, of whom 4 required colostomies. The overall incidence of perioperative complications was 17 per cent. There was one postoperative death.     

Salvage cystectomy

This report presents the results of 40 salvage cystectomies performed after failure of radiation therapy to control the disease in patients with bladder cancer. All patients had failure or recurrence after 7,000 rad. The time between end of radiation therapy and cystectomy was three to six months in 11 patients, seven to twelve months in 15, thirteen to twenty-four months in 8, and longer than thirty-six months in 6. There were two immediate and four late postoperative deaths. A total of twenty-two complications occurred in 16 patients. The five-year survival rate was 100 per cent for patients with in situ carcinoma, 58 per cent for Stage A disease, 50 per cent for Stage B1, and 40 per cent for Stage B2 disease. There were no survivors among patients with Stages C and D1 disease. Salvage cystectomy, although associated with significant morbidity, remains a viable form of therapy for patients in whom definitive radiotherapy fails.     

Symptomatic stage c carcinoma of prostate: Traditional therapy

Of 119 consecutive patients with adenocarcinoma of the prostate, 54 patients had clinical Stage C disease and are the subject of this study. Of these 54 patients, 52 underwent transurethral prostatectomy and bilateral orchiectomy as their initial treatment; estrogens were not prescribed. The mean age of the patients with Stage C disease was seventy-three years, the average survival 6.4 years, and the five and ten-year survivals were 66 and 20 per cent, respectively. Stage C patients treated in this series did as well as those treated with radiation or radical extirpation.     

Bilateral pelvic lymphadenectomy and radical retropubic prostatectomy for stage C adenocarcinoma of prostate

A series of 105 patients with surgical Stage C adenocarcinoma of the prostate underwent pelvic lymphadenectomy and radical retropubic prostatectomy and were followed up from one and one-half to fifteen years; 33 (31%) of the 105 had clinical Stage C disease. Of the 105 patients, 92 were at risk for greater than or equal to two years, 42 for greater than or equal to five years, and 12 for greater than or equal to ten years. Survival and disease progression were related to tumor grade (Mayo grades 1 through 4) and tumor bulk (less than 3, 3 to 10, greater than 10 cm3) but not to seminal vesicle involvement. Twenty-seven patients received adjuvant treatment (orchiectomy, DES, radiation, or combinations of these); it was administered to patients with higher tumor grades, larger tumor bulk, and/or residual cancer. Overall actuarial survival at five and ten years was 85 per cent and 72 per cent, respectively; five-year nonprogression rate was 64 per cent. Local recurrence was noted in only 8 patients (7.6%). Radical surgical treatment for nonbulky Stage C disease of the prostate is associated with favorable survival results and good local control. Adjuvant treatment may favorably affect disease outcome. Clinical seminal vesicle involvement with negative urethrocystoscopy should not necessarily deter the surgeon from planning radical prostatectomy. Prospective adjuvant treatment protocols need to be developed to identify the value of adjuvant hormone and/or radiation therapy.     

Radical prostatectomy. Patterns of local failure and survival in 67 patients

Sixty-seven patients with localized carcinoma of the prostate were treated by radical prostatectomy unaided by adjunctive hormonal therapy. Seven patients (10%) have been lost to follow-up, and 13 patients (19%) have died of other causes without evidence of prostate cancer. The crude or direct survival free of disease for traced patients with clinical Stage B1 nodules (11) and clinical B2 lesions (20) followed for at least fifteen years is 36 per cent and 25 per cent, respectively; the crude or direct survival free of disease for pathologic B (29) and C (12) tumors followed for fifteen years is 31 per cent and 8 per cent, respectively. The local failure incidence at fifteen years for pathologic Stage B tumors is 17 per cent and for pathologic C tumors 31 per cent. Capsular invasion alone on histologic examination did not increase the rate of local or distant failure above that noted for tumors that were entirely intracapsular. However, seminal vesicle invasion is associated with a 44 per cent local failure and 66 per cent distant failure rate. The interval between radical prostatectomy and first failure averaged sixty-nine months (median 56 months) and with hormonal therapy the interval between first failure and death averaged seventy months (median 62 months). The patients who underwent radical prostatectomy in this series represent 22 per cent of the 318 patients presenting with localized prostate cancer between 1960 and 1974. A 1.5-cm nodule was found in 5.5 per cent of the presenting population, and all but one of these patients were treated by radical prostatectomy.     

Understaging and undergrading of prostate cancer. Argument for postoperative radiation as adjuvant therapy

This report reviews the staging and grading errors that occurred in a consecutive series of 14 patients treated for prostate cancer by radical prostatectomy and of 58 patients treated by both radical prostatectomy and pelvic lymphadenectomy. Almost half of the patients who were in Stages A2, B1, or B2 by clinical criteria were in pathologic Stage C when both capsular perforation and seminal vesicle invasion were used as the criteria for Stage C disease. Seminal vesicle invasion was the more important prognostic factor. Moreover, the pathologic grade of cancer, as determined by needle or transurethral biopsy, was underestimated in 39 per cent of the cases; when the grade was corrected, the patient often was in a worse prognostic group than the one originally assigned. Thus, in this series, more than 40 per cent of the patients were at high risk of persistent or recurrent disease after radical prostatectomy. Radiation was given after operation to 22 such high-risk patients and was well tolerated.     

Comparison of whole pelvis versus small-field radiation therapy for carcinoma of prostate

One hundred thirty-six patients with adenocarcinoma of the prostate gland Stage A2 (12 patients), Stages B1 and B2 (26), Stage C (64), and Stages D1 and D2 (34 patients) were evaluated clinically and treated in a similar fashion at three hospitals. Megavoltage radiation therapy units were employed to deliver 4,600-5,000 cGy to the whole pelvis, and the prostatic area was treated for an additional 2,000 cGy (boost). Local recurrence was infrequent (8/136 = 6%), and the five-year actuarial survival and disease-free survival rates were 85 and 42 per cent, respectively. Adverse clinical parameters included poor histologic differentiation, age younger than sixty years, and diagnosis by transurethral resection of the prostate rather than needle biopsy in Stage C patients. Severe acute reactions occurred in only 2 patients, and only 2 patients were hospitalized for severe chronic (late) reactions. Whole pelvis radiation yielded a statistically significant improved five-year survival and three-year disease-free survival for similarly evaluated patients for Stage C but not for Stages A and B when compared with 116 patients treated with small-volume radiation (prostate area), previously reported from these three hospitals.     

Transurethral resection versus needle biopsy prior to radical prostatectomy for stage C prostate cancer. Influence on progression and survival

Previous reports have claimed that transurethral resection of the prostate (TURP) preceding definitive radiation therapy for patients with Stage C prostate cancer promotes the risk of distant metastasis and increases the mortality rate. A total of 490 patients with pathologic Stage C adenocarcinoma of the prostate treated by radical prostatectomy were studied. Median time to follow-up was 4.6 years. Comparison was made between patients who had TURP within the six months preceding prostatectomy (n = 54) and those who had needle biopsy (n = 437) prior to operation. No significant differences were noted in local recurrence of disease, systemic progression of disease, disease-free interval, and overall and cause-specific survival, even after adjustment for clinical (adjuvant treatment) and pathologic prognostic variables. Our data suggest that for patients with pathologic Stage C prostate cancer treated by radical surgery, preoperative TURP is not associated with unfavorable outcome.     

Adjuvant radiotherapy following radical prostatectomy: results and complications

Between 1954 and 1978, 148 patients underwent radical perineal prostatectomy for adenocarcinoma clinically confined to the prostate gland. This report is based on 45 of these patients with microscopic extension of disease beyond the gland and a minimum 5-year followup. Of the patients 22 received adjuvant external beam radiation therapy and 23 did not. The groups were comparable with regard to significant prognostic variables. Patient selection was by surgeon preference. Local recurrences were seen in 1 of 22 patients (5 per cent) receiving adjuvant radiotherapy and 7 of 23 (30 per cent) undergoing an operation alone (p less than 0.05). Of 8 patients with local recurrence 7 died of the disease. Delayed radiotherapy of a local recurrence generally was not effective in controlling the disease. Of the 11 patients who died of prostatic cancer with a mean followup of 9.2 years 3 received adjuvant radiotherapy and 8 did not. Severe but nonfatal long-term complications were seen in 14 per cent of the irradiated patients and 6 per cent of those treated with an operation alone. Most of the complications occurred in the earlier years of the study in patients who received 60cobalt radiotherapy. When clinical stage B cancer of the prostate is found to be pathological stage C following radical perineal prostatectomy, adjuvant radiotherapy can decrease the incidence of subsequent local recurrence. The potential risk of adjuvant radiation therapy should be weighed and its use considered, particularly in patients whose tumor extends to the surgical margins or who have seminal vesicle invasion.     

Predictors of secondary cancer treatment in patients receiving local therapy for prostate cancer: data from cancer of the prostate strategic urologic research endeavor

PURPOSE: Secondary cancer treatment is common after definitive local therapy for prostate cancer and it may be an indicator of the efficacy and cost of primary local treatment. We determined predictors of secondary cancer treatment in patients initially treated with radical prostatectomy or external beam radiation. MATERIALS AND METHODS: We examined 2,336 patients in Cancer of the Prostate Strategic Urologic Research Endeavor, a longitudinal registry of patients with prostate cancer, who underwent initial treatment with radical prostatectomy (1,744) or external beam radiation (592). Patients had at least 1 month of followup and all pretreatment information was available. The percent of patients receiving secondary cancer treatment, time to secondary treatment and type of secondary treatment delivered was determined. Multivariate analysis was done to determine independent predictors of secondary cancer treatment. In patients initially treated with prostatectomy a similar analysis was performed to identify predictors of receiving androgen deprivation versus radiation. RESULTS: A total of 590 patients (25%) received secondary cancer treatment, including prostatectomy in 391 (22%) and radiation in 199 (34%). Secondary cancer treatment was equally divided between radiation and androgen deprivation in 52% and 47%, respectively, of those initially treated with prostatectomy, while 92% initially treated with radiation received androgen deprivation. Predictors of any secondary treatment included patient age, biopsy Gleason score and prostate specific antigen at diagnosis. There was a trend toward increased secondary treatment more than 6 months after local therapy in patients initially treated with radiation. Increased age and lymph node metastases were independent predictors of receiving androgen deprivation after prostatectomy, while there was increased use of radiation in patients with positive surgical margins or extracapsular disease extension. CONCLUSIONS: Secondary treatment differs in patients initially treated with radical prostatectomy and radiation. Pretreatment factors can be used to counsel patients regarding the likelihood of secondary treatment, while age and prostatectomy results appear to determine the type of secondary treatment in those initially treated with prostatectomy.     

Adjuvant radiation therapy in stages C and D1 prostatic adenocarcinoma: preliminary results

Twenty patients with adenocarcinoma of the prostate underwent postradical prostatectomy adjuvant external beam megavoltage radiation therapy because of periprostatic disease in histologic evaluation of the resected specimen. Fourteen of these patients had pathologic Stage C and 6 pathologic Stage D1 disease. Treatment in most patients consisted of 5,000 rad delivered to the true pelvis. The five-year recurrence-free survival was 75 per cent for pathologic Stage C and 41 per cent for Stage D1 disease. The median time to first evidence of treatment failure was fifty months for D1 patients and has not been reached by the C group. Minor complications occurred in 85 per cent of patients and major complications in 5 per cent. In 1 patient with mild, postoperative stress incontinence total urinary incontinence developed after radiation therapy. These preliminary observations suggest a prolonged disease-free interval with an acceptable morbidity is obtained utilizing this regimen.     

Controversies in management of stages I and II testicular seminomas

The general success in treating seminoma (Stages I and II) of the testicle has prompted questions regarding the extent of treatment that these patients require. We reviewed 79 patients treated at NYU/Bellevue Medical Center from 1965 to 1984 to establish a data base from which the controversies surrounding this disease can be viewed. Standard treatment involved a radical inguinal orchiectomy as primary therapy. Stage I patients received adjuvant radiation to para-aortic and ipsilateral iliac nodes, with additional radiation given routinely to the mediastinum of patients with Stage II disease. No major complications were observed. All Stage I patients remain free of recurrent tumor with a median follow-up of eight years. There were 4 deaths from seminoma among the Stage II patients. The use of prophylactic mediastinal radiation for Stage II patients, and observation only for Stage I patients are reviewed in light of our results and other published series. While early evidence suggests that both approaches may be reasonable, their adoption awaits confirmation by prospective trial.     

Intermediate-term survival results in clinically understaged prostate cancer patients following radical prostatectomy

To determine the natural history of clinically understaged prostatic cancer patients who were followed without adjuvant therapy for at least 6 years after radical prostatectomy we reviewed the clinical courses of 21 patients (1 with clinical stage A and 20 with clinical stage B disease). All patients underwent radical retropubic prostatectomy and 9 had pathological stage C disease (6 with capsular penetration only and 3 with seminal vesicle invasion). A total of 12 patients had pathological stage D1 disease by virtue of positive nodes on permanent sections after frozen sections were read as negative. Among the patients with pathological stage C disease 67 per cent were free of recurrence 6 years after radical prostatectomy. Of the patients with seminal vesicle invasion 33 per cent had recurrence compared to 17 per cent of those with capsular penetration only. Among the 12 stage D1 cancer patients 75 per cent were free of recurrence at 6 years. In both groups patients who were followed beyond 7 years had a diminished survival free of tumor owing to late tumor recurrences. The results indicate that the intermediate survival rates free of tumor in patients with clinically understaged A or B prostatic cancer are remarkably good without adjuvant therapy. However, survival without recurrence appears to decrease after 7 years. All patients who failed treatment did so distantly; no patient failed with local recurrence alone. These results may be important in the evaluation of adjuvant therapy protocols currently under investigation for patients with clinically understaged prostate cancer.     

Early results of radical prostatectomy and adjuvant endocrine therapy for prostate cancer with or without preoperative androgen deprivation

Background : The effects of preoperative androgen deprivation were explored in the patients who received radical prostatectomy and subsequent adjuvant endocrine therapy for prostate cancer.
Methods: Stage A₂, B or C prostate cancers were randomized to one of two groups: (i) group I ( n = 90), who received androgen deprivation (leuploride and chlormadinone acetate) for 3 months preoperatively followed by radical prostatectomy and adjuvant endocrine therapy (leuploride only); and (ii) group II ( n = 86), who underwent the surgery followed by 3 month androgen deprivation and subsequent adjuvant endocrine therapy. The effects of preoperative androgen deprivation on clinical relapse (serum prostate specific antigen (PSA) > 1.98 ng/mL, local recurrence or distant metastasis) and PSA relapse (PSA > 0.2 ng/mL) were evaluated at 2 years after randomization.
Results: There was no significant difference in clinical or PSA relapse-free survival and quality of life measures between the two groups, although relapses occurred significantly more frequently in patients who had more advanced stages, higher pretreatment PSA values or lower histologic differentiation in either group. Subgroup analysis indicated that clinical relapse-free survival in stage C cancer tended to be better in patients with preoperative androgen deprivation than in those patients without it ( P < 0.1).
Conclusions : Preoperative androgen deprivation may be beneficial for stage C prostate cancer patients receiving radical prostatectomy and adjuvant endocrine therapy over the 2 year observation period. A longer follow up is needed to clarify the exact extent of benefit in terms of survival and quality of life.     

Long-term survival in men with high grade prostate cancer: a comparison between conservative treatment, radiation therapy and radical prostatectomy--a propensity scoring approach

PURPOSE: We performed a retrospective cohort study using propensity score analysis to calculate long-term survival in patients with prostate cancer with Gleason score 8 or greater who were treated with conservative therapy, radiation therapy and radical prostatectomy. MATERIALS AND METHODS: Between January 1, 1980 and December 31, 1997, 3,159 patients in the Henry Ford Health System were diagnosed with clinically localized prostate cancer. Of these patients 453 had a Gleason score of 8 or greater in the biopsy specimen and they were the cohort. The end points were overall and prostate cancer specific survival. Propensity score analysis was used to more precisely compare the 3 treatments of observation, radiation and radical prostatectomy. Median patient followup was longer in the radical prostatectomy arm than in the conservative treatment and radiation therapy arms (68 months vs 52 and 54, respectively). RESULTS: Of the 453 patients 197 (44%) were treated conservatively, 137 (30%) received radiation therapy and 119 (26%) underwent radical prostatectomy. Using propensity scoring analysis median overall survival for conservative therapy, radiation and radical prostatectomy was 5.2, 6.7 and 9.7 years, respectively. Median cancer specific survival was 7.8 years for conservative therapy and more than 14 years for radiation therapy and radical prostatectomy. The risk of cancer specific death following radical prostatectomy was 68% lower than for conservative treatment and 49% lower than for radiation therapy (p<0.001 and 0.053, respectively). CONCLUSIONS: Survival of men with high grade prostate cancer can be improved by radical prostatectomy or radiation therapy.     

Does radical prostatectomy in the presence of positive pelvic lymph nodes enhance survival?

Summary A retrospective review was performed on all patients with stage D1 prostate cancer treated at Duke University Medical Center between 1975 and 1989. A total of 156 patients underwent staging pelvic lymph-node dissection for clinically organ-confined prostate cancer (stage A or B) but were found to have disease metastatic to the pelvic lymph nodes (stage D1). Of this population, 42 patients also underwent radical prostatectomy (group 1), leaving 114 who did not have their prostate removed (group 2). The median cancer-specific survival was 11.2 years for group 1 versus 5.8 years for group 2 (P=0.005). In patients with one or two positive lymph nodes the median cancer-specific survival was 10.2 years for group 1 versus 5.9 years for group 2 (P=0.015). There was no difference in survival if three or more lymph nodes were positive. Adjuvant treatment with immediate androgen deprivation and/or postoperative radiation therapy failed to improve the survival experience. The incidence of local problems, including stricture formation, bleeding, or regrowth of cancer requiring dilation or surgical intervention (transurethral prostatectomy) averaged 9.5% in group 1 and 24.6% in group 2. These data show that patients with limited node-positive disease selected for radical prostatectomy experience a survival advantage over those denied such therapy and that this advantage is independent of adjunctive therapy.This research was performed while Dr. Frazier was serving as a fellow in Urologic Oncology with funding from the United States Navy. The opinions herein represent those of the authors and do not necessarily reflect those of the United States Navy or the Department of Defense     

Evaluation of partial cystectomy for carcinoma of bladder.

We reviewed 117 patients who had undergone partial cystectomy for primary carcinoma of the bladder. The recurrence rate was 78 per cent. Treatment of recurrences included transurethral resection, radiation therapy, and total cystectomy. The five-year survival rate of patients treated for recurrent disease was 68 per cent for Stages 0 and A, 31 percent for Stage B, and 6 per cent for Stages C and D1. Total cystectomy gave the best salvage rate. The five-year survival rate of patients without recurrences was 4 per cent.     

Salvage radical prostatectomy for radiorecurrent prostate cancer: morbidity revisited

PURPOSE: With the advent of prostate specific antigen (PSA) testing and transrectal ultrasound guided prostate biopsy there has been stage migration in the diagnosis of prostate cancer, so that more younger men are being diagnosed with organ confined prostate cancer. Many patients elect radiation therapy, while some have recurrent or new prostate cancer with absent systemic disease and life expectancy greater than 10 years. We present our experience with salvage radical prostatectomy in these cases. MATERIALS AND METHODS: Between 1995 and 2000, 6 men treated with curative intent with radiotherapy for prostate cancer were subsequently treated with salvage surgery for clinically localized prostate cancer. All men had biopsy proved recurrent or persistent prostate cancer, increasing serum PSA, no evidence of systemic disease at surgery and life expectancy greater than 10 years. We assessed the morbidity associated with this procedure and compared results to those in the contemporary literature. RESULTS: Six patients underwent salvage radical prostatectomy. Initial pre-radiation PSA was 4.5 to 15.7 ng./ml. Pre-radiation disease was clinical stage T1c in 5 cases and B2 in 1. The interval from radiotherapy to repeat biopsy was 12 to 48 months. A mean of 6.3 months after local recurrence was detected and before salvage radical prostatectomy was performed 4 patients underwent androgen deprivation therapy. Mean operative time was 195 minutes, intraoperative blood loss was 680 cc, and hospital stay and catheterization time were 3.2 and 13.8 days, respectively. There were no rectal injuries. All 6 patients are impotent, 5 are continent and 1 has mild stress incontinence. There was biochemical failure in 1 case 36 months after salvage radical prostatectomy and no evidence of recurrence in the remaining 5 at a mean followup of 27 months. CONCLUSIONS: Salvage radical prostatectomy is a technically challenging procedure. In the past it was associated with a high incidence of rectal injury, urinary incontinence and anastomotic stricture. The results of our relatively small series are encouraging and concur with those of recent studies that the morbidity of salvage radical prostatectomy is lower than previously reported. We believe that salvage radical prostatectomy may be considered a reasonable treatment option in appropriate patients with radiorecurrent prostate cancer.