Harold A. Frazier

Radical Cystectomy for Stages TA, TIS and T1 Transitional Cell Carcinoma of the Bladder

Between January 1969 and January 1990, 531 patients underwent bilateral pelvic lymph node dissection and radical cystectomy for the management of transitional cell carcinoma of the bladder. Of these procedures 220 were performed for clinical stage Ta (31 patients), Tis (23) or T1 (166) disease, which was either high grade or recalcitrant to transurethral resection and/or intravesical chemotherapy. This subgroup of patients was studied to evaluate the outcome of recurrent or chemotherapy resistant superficial transitional cell carcinoma of the bladder after radical cystectomy. The operative mortality rate for the group was 2.3% and the overall complication rate was 20.4%. The pelvic recurrence rate was 5.9%. The 5-year cancer-specific survival rates for patients with pathological stage Ta (11), Tis (19), T0 (43) and T1 (91) disease were 88%, 100%, 80% and 76%, respectively. The 10-year cancer-specific survival rates were 75%, 92%, 66% and 62%, respectively. A total of 74 patients received preoperative radiation therapy (2,000 rad) but they had no better 5-year cancer-specific survival rates than did nonirradiated patients. Transurethral resection and/or preoperative radiation therapy resulted in a pathological status of T0 in 43 patients but this did not confer a survival advantage. Although bladder preservation is preferable, low operative mortality and pelvic recurrence rates, as well as new methods of continent urinary diversion continue to make radical cystectomy the definitive form of therapy for patients with superficial disease recalcitrant to transurethral therapy.

The value of pathologic factors in predicting cancer‐specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate

Background. A recent consensus conference on bladder carcinoma highlighted the need for pathologic predictors of outcome for patients with transitional cell carcinoma of the bladder. This review was undertaken to determine the pathologic features predictive of cancer‐specific survival after a radical cystectomy and urinary diversion for transitional cell carcinoma of the bladder and prostate.

Complications of Radical Cystectomy and Urinary Diversion: A Retrospective Review of 675 Cases in 2 Decades

A retrospective review was performed on all 675 patients who underwent radical cystectomy and urinary diversion during 2 decades. Of the patients 197 were treated from 1969 to 1979 (group 1) and 478 were treated from 1980 until 1990 (group 2). The mean age of patients in group 1 was 56.7 years versus 64.2 years in group 2 (p < 0.001). The overall operative mortality rate in both groups was 2.5%. A total of 215 patients (31.9%) experienced postoperative complications (within 30 days of surgery). The morbidity rate was nearly identical between the 2 groups (32.0% for group 1 versus 31.8% for group 2, p = 0.962). Of note, however, there was a decreased incidence of wound infections and wound dehiscence among the patients in group 2 compared to group 1. Long-term complications occurred in 198 of the 675 patients (29.3%). At followup group 1 had a 35.5% incidence of long-term complications versus 26.8% in group 2 (p = 0.022). Most notably there was significant improvement in the incidence of ureteroenteric anastomotic strictures when comparing groups 1 (11.2%) and 2 (5.2%) (p = 0.006).

Immunoreactive prostatic specific antigen in male periurethral glands.

Prostatic specific antigen (PSA) is considered an antigen unique to benign and malignant prostatic tissue. Recent evidence in the literature has raised serious doubts about the specificity of this antigen. In this study twenty male urethral specimens were evaluated for PSA and prostatic acid phosphatase (PAP) from patients without evidence of prostatic cancer. Eight of these 20 urethral specimens exhibited strong immunostaining for both PSA and PAP, localized in the periurethral glands. Five of the 17 urethral biopsies were positive for both antigens, while all three of the whole mount autopsy specimens stained positive for PSA and PAP. Within the autopsy series, there was heterogenous staining of the periurethral glands within the same specimen. This evidence disproves the fact that PSA and PAP are organ specific as previously described. More than likely any tissue of cloacal origin has potential for staining positive for prostatic specific antigen and prostatic acid phosphatase.

Radical Prostatectomy: the Pros and Cons of the Perineal Versus Retropubic Approach

Radical prostatectomy is frequently recommended for the treatment of localized adenocarcinoma of the prostate. The use of the perineal versus the retropubic approach is mostly dependent upon the experience of the individual surgeon. This study was performed to evaluate the short-term differences between the 2 operations. Between 1988 and 1989, 173 patients were identified with organ confined prostate cancer (stage A or B) who were treated with radical prostatectomy. Of this total population 122 patients underwent radical perineal prostatectomy (group 1) and 51 patients underwent radical retropubic prostatectomy (group 2). The median estimated blood loss for group 1 was 565 cc and for group 2 it was 2,000 cc (p less than 0.001). Group 1 received a median of 0 units of blood during hospitalization, while group 2 received a median of 3 units of blood (p less than 0.001). The total operative time was slightly shorter for group 1 but the anesthesia time was similar for both patient populations. There was no difference in the incidence of positive surgical margins, and in in-hospital and long-term complication rates between the 2 groups. In light of these significant findings it is our belief that the radical perineal prostatectomy is an excellent approach for the treatment of adenocarcinoma of the prostate.

Clinical variables which serve as predictors of cancer-specific survival among patients treated with radical cystectomy for transitional cell carcinoma of the bladder and prostate

Background. Studies have demonstrated conclusively that the stage and grade of transitional cell tumors at presentation are major determinants of survival for those with the disease in the bladder and prostate. The authors initiated a review of 531 patients with transitional cell carcinoma of the bladder and prostate treated with radical cystectomy between 1969 and 1990 to identify other clinical features predictive of cancer‐specific survival.

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

SummaryA 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.

Does a Stage pT0 Cystectomy Specimen Confer a Survival Advantage in Patients with Minimally Invasive Bladder Cancer

Controversy exists regarding the clinical significance of a pathological stage T0 (pT0) specimen found at cystectomy or after repeat transurethral resection for transitional cell carcinoma of the bladder. Many investigators cite this subpopulation of patients as a reason to consider more conservative management, based on the premise that the patient may have benefited from the original transurethral resection. However, we questioned whether outcome would be improved in stage pT0 cancer patients or whether outcome in stage pT0 cases would parallel that noted when the original stage was equivalent to the final pathological stage. To test this hypothesis, we examined the survival advantage occasioned by a stage pT0 finding in 66 of 433 patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. Of the 433 patients studied 54 had clinical stage Tis or Ta, 166 clinical stage T1 and 213 clinical stage T2 disease. Within each of the 3 clinical groups (clinical stage Tis/Ta, clinical stage T1 and clinical stage T2) Kaplan-Meier survival projections were generated comparing patients with stage pT0 disease to those whose pathological stage was identical to the original clinical stage. Among the 54 clinical stage Tis/Ta cancer patients 11 with stage pT0 and 24 with stage pTis/pTa had survival projections of 90% of 5 years. Of 166 patients with clinical stage T1 disease 32 with stage pT0 and 78 with stage pT1 tumor had survival projections of 75% at 5 years. Among 213 patients with clinical stage T2 cancer 23 with stage pT0 and 71 with stage pT2 disease had survival projections of 68% at 5 years. The data suggest that a stage pT0 cystectomy specimen does not confer a survival advantage over that noted from the initiating population in which the final pathological stage and initial clinical stage are equivalent. A patient with a stage pT0 specimen functions, by survival analysis, in a manner similar to one with the stated clinical stage.

Androgen Receptor-Target Genes in African American Prostate Cancer Disparities

The incidence and mortality rates of prostate cancer (PCa) are higher in African American (AA) compared to Caucasian American (CA) men. To elucidate the molecular mechanisms underlying PCa disparities, we employed an integrative approach combining gene expression profiling and pathway and promoter analyses to investigate differential transcriptomes and deregulated signaling pathways in AA versus CA cancers. A comparison of AA and CA PCa specimens identified 1,188 differentially expressed genes. Interestingly, these transcriptional differences were overrepresented in signaling pathways that converged on the androgen receptor (AR), suggesting that the AR may be a unifying oncogenic theme in AA PCa. Gene promoter analysis revealed that 382 out of 1,188 genes contained cis-acting AR-binding sequences. Chromatin immunoprecipitation confirmed STAT1, RHOA, ITGB5, MAPKAPK2, CSNK2A,1 and PIK3CB genes as novel AR targets in PCa disparities. Moreover, functional screens revealed that androgen-stimulated AR binding and upregulation of RHOA, ITGB5, and PIK3CB genes were associated with increased invasive activity of AA PCa cells, as siRNA-mediated knockdown of each gene caused a loss of androgen-stimulated invasion. In summation, our findings demonstrate that transcriptional changes have preferentially occurred in multiple signaling pathways converging (“transcriptional convergence”) on AR signaling, thereby contributing to AR-target gene activation and PCa aggressiveness in AAs.

Total Prostatoseminal Vesiculectomy in the Treatment of Debilitating Perineal Pain

Persistent perineal pain, unresponsive to antibiotics and analgesia, sufficient to produce an inability to function in any work or social environment is occasionally encountered. A total of 5 such patients underwent total prostatoseminal vesiculectomy: 3 experienced complete relief of the pain and 1 experienced symptomatic relief to the extent that he ranks the residual discomfort as 1 on a scale of 1 to 10. The remaining patient had complete absence of pain for approximately 4 months but thereafter mild, intermittent proximal urethral discomfort developed during voiding. Total prostatoseminal vesiculectomy may be occasionally applicable in the patient disabled by chronic perineal pain. We believe that psychiatric evaluation and concurrence should be a preoperative prerequisite.