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The purpose of the present study was to examine the outcome profiles of a large number of patients with locally advanced adenocarcinoma of the prostate following radical perineal prostatectomy (RPP) for clinically organ-confined disease. Of 1662 men who underwent RPP performed by a single surgeon between January 1972 and January 1999, 692 patients (41.6%) aged a median of 66.1 years were found to have extracapsular disease on pathological evaluation. The extent of disease was categorized as either specimen-confined (n = 355) or margin-positive (n = 337). The histological grade of the cancer was characterized using the Gleason score. Time to biochemical failure, defined as a prostate-specific antigen (PSA) level ofor = 0.5 ng/ml, and cancer-associated survival were the end points of our outcome analysis using the Kaplan-Meier product-limit method. The median time to cancer-associated death for patients with specimen-confined and margin-positive disease was 18.5 and 13.1 years, respectively. After 5 years, 37% and 54% of the patients with specimen-confined and margin-positive disease, respectively, had PSA failure. Prostate cancer patients with a Gleason score of 5-6, 7, and 8-10 experienced a median time to cancer-associated death of 19.9, 19.2, and 10.5 years, respectively. A subset of patients undergoing adjunctive radiation therapy (XRT) relapsed biochemically after a median period of approximately 18 months. RPP provides a substantial disease-control benefit in patients with specimen-confined cancer. The time to biochemical failure and the time to cancer-associated death are significantly influenced by the biology of the underlying disease, necessitating long-term follow-up in the outcome analysis of any modality of treatment for prostate cancer. A benefit of early adjunctive XRT for local failure remains to be determined.

We examined 4 postulates: 1) radical perineal prostatectomy provides a substantial disease control benefit in men with clinically confined prostate cancer, 2) postoperative prostate specific antigen (PSA) levels are an excellent surrogate end point for defining disease control, 3) the biology of primary malignancy defines the interval to death after recurrence and 4) the interval from intervention to death from recurrence is so long that current series of alternative curative therapies have insufficient duration of observation to permit a comparison with the results of surgery.A total of 1,242 men with a median age of 65.2 years who had stage cT1 to 2 N0M0 disease underwent radical perineal prostatectomy. The final pathology specimen was characterized in regard to disease extent, and Gleason grade and score. Patients were followed at 2 weeks, at 2 months and then at 6-month intervals for biochemical, physical and radiographic evidence of disease recurrence. Outcome was evaluated by determining time to biochemical failure (PSA 0.5 ng./ml. or greater) and cancer associated death.Median time to noncancer death was 19.3 years. Median cancer associated death end point was not reached by patients with organ and specimen confined disease, while it was 12.7 years for margin positive disease. At 5 years 8, 35 and 65% of the patients with organ confined, specimen confined and margin positive disease, respectively, had PSA failure. This served as an excellent surrogate end point, preceding cancer associated death by 5 to 12 years depending on the biological aggressiveness predicted by Gleason grade or score. Biologically aggressive organ confined disease that had been surgically removed was associated with a high percentage of disease-free survival.Our study confirms our postulates. It also provides guidelines for comparing therapies among institutions and emphasizes that enthusiasm for new treatments may be based on insufficient followup. Patient selection may severely bias outcome independent of treatment when death is used as the end point. Our study establishes the value of PSA as a surrogate end point.

Few studies have compared the outcome of radical prostatectomy between African-American males (AAM) and white males, and the results of the few studies that have are conflicting. Therefore, the authors examined the impact of radical surgery on localized prostate carcinoma in both patient populations, and assessed whether stratification by pathologic extent of local disease would yield an equivalent outcome.

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.

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.

SUMMARY. The purposes of the present work were to identify the initial characteristics associated with long-term survival in chronic granulocytic leukaemia (CGL) and to analyse the accuracy of prognostic models in identifying long-term survivors. 813 Philadelphia (Ph) chromosome-positive, nonblastic CGL patients from six American and European institutions, the majority treated conventionally, with a minimum follow-up < 10 years, were studied. Stepwise logistic regression was performed to ascertain the association between the initial clinicohaematological variables and survival ≤8 years, and a prognostic index was derived. The usefulness of both Sokal's and the new prognostic index to identify long-term survivors was assessed by calculating their positive and negative predictive accuracies, sensitivity and specificity. Median survival of the series was 45 months (range 1-255), with 784 patients (96.4%) having died and 109 (13.4%) surviving 8 years or longer. Younger age, smaller spleen, platelets ≤600 × 109/I, and lower blood blast percentage were associated with survival ≤8 years; platelets ≤ 600 × 109/I and lower blood blast percentage were the predictive factors in patients 50 years old or younger. Two-thirds of long survivors belonged to Sokal's low-risk group, but the positive predictive accuracy and specificity for prolonged survival of Sokal's index were very low. This was also the case for the new predictive index. In 366 patients with information on the presence or not of additional karyotypic abnormalities at diagnosis, younger age, platelets ≤ 600 × 109/I, lower blood blast percentage, and absence of additional cytogenetic abnormalities were associated with survival ≤8 years. The addition of the cytogenetic data improved the positive predictive accuracy and specificity of the model, albeit modestly. We conclude that, although most CGL long survivors show favourable prognostic features at presentation, clinicohaematological data do not allow a precise definition of such a subpopulation.

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. Materials and Methods. Inpatient and clinical medical records were analyzed for age, race, gender, clinical T stage, medical history, and presenting symptoms and signs, and admission laboratory values were correlated with the patient's cancer-specific outcome. Both univariate and multivariate analyses of the various clinical factors were performed to identify variables predictive of cancer-specific survival. Results. Univariate analysis indicated that clinical T classification, preoperative hemoglobin, tumor grade, irritative voiding symptoms, age, preoperative creatinine, obstructive hydronephrosis on preoperative excretory urography, a history of bladder tumors or nephrour-eterectomy for transitional cell cancer, prior urinary tract infections, prior pelvic irradiation, and obstructive symptoms were all predictive of poor cancer-specific survival. Multivariate analysis demonstrated that higher clinical T classification (T2, T3a, T3b, T4 versus Ta, Tis, T1) (P 65 years versus 12 gm/dl) (P < 0.001), higher preoperative creatinine level (≥ 1.5 mg/dl versus < 1.5 mg/dl) (P = 0.002), a history of nephroureterectomy for transitional cell cancer (P = 0.016), and a history of pelvic irradiation (P = 0.002) were all predictive of poor cancer-specific survival. Conclusions. Although clinical T classification and tumor grade remain the best predictors of survival in patients with transitional cell carcinoma of the bladder or prostate, clinical variables such as age, preoperative creatinine and hemoglobin levels, a history of nephroureterectomy or pelvic irradiation, and irritative voiding symptoms at presentation may provide additional prognostic information independent of tumor grade and stage.

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.

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. Methods. Between 1969 and 1990, 531 patients with transitional cell carcinoma of the bladder and prostate were treated with radical cystectomy at the Duke University Medical Center. Records and pathologic specimens were analyzed and correlated with outcome. Both univariate and multivariate analyses of the pathologic staging were performed to identify variables predictive of cancer-specific survival. Results. Univariate analysis indicated that pathologic tumor (pT) stage, positive nodes, positive surgical margins, prostatic stromal involvement, grade, age, ureteral involvement, squamous cell carcinoma, and squamous cell differentiation in the specimen all were predictive of poor cancer-specific survival. Carcinoma in situ (CIS) in the specimen was not an adverse prognostic indicator. Multivariate analysis demonstrated that the pT stage, nodal involvement, positive surgical margins, patient's age at surgery, and loss of histologic differentiation were predictive of poor cancer-specific survival. CIS was found again not to have a negative influence on cancer-specific survival. Conclusions. If any of these features are noted in the final pathologic specimen, patients should be considered for some form of additional postoperative treatment such as chemotherapy or radiation therapy in an attempt to improve their chances for cancer-free survival. These factors will become more important in selecting which patients should be placed in developing adjuvant clinical trials.

A total of 44 patients with renal cell carcinoma and vena caval tumor thrombus underwent surgical resection. Of these patients 27 had primary tumor confined within Gerota's fascia, negative lymph nodes and no distant metastases (stage T3cN0M0). Patients who underwent extraction of a mobile tumor thrombus from the vena cava had a 69% 5-year survival rate (median 9.9 years) but patients with tumor thrombus directly invading the vena cava had a 26% 5-year survival rate (median 1.2 years), which improved to 57% (median 5.3 years) if the involved vena caval side wall was resected successfully. Of these patients 17 had renal cell carcinoma with vena caval thrombus as well as extrafascial extension, regional lymphadenopathy or distant metastases, and the 5-year survival rate was less than 18% in all groups (median survival less than 0.9 years). Prognosis was determined by the pathological stage of the renal cell carcinoma and by the presence or absence of vena caval side wall invasion but not by the level of tumor thrombus extension. Patients with incomplete resection of localized renal cell carcinoma with tumor thrombus do not survive any longer than those with extensive cancer, positive lymph nodes or distant metastases. However, when partial venacavectomy establishes negative surgical margins then survival markedly improves.

A group of 159 patients previously reported as having margins positive for disease after radical prostatectomy with or without adjunctive postoperative radiation was reanalyzed to determine whether the reported benefit did indeed exist. Upon re-examination of the 159 patients 15 were identified who did not receive radical prostatectomy but who were analyzed as if they had received this therapy. An updated review of the total pool of 159 patients with analysis as to failure, death of any cause or death of prostatic cancer demonstrated no benefit of postoperative radiation therapy for margin positive disease. Exclusion of patients who did not receive radical prostatectomy and analysis as described also failed to identify any benefit of postoperative adjunctive radiation therapy.

Current bias would conclude that elevation of serum prostate specific antigen (PSA) after radical prostatectomy infers failure of the procedure. Since April 1987 preoperative and postoperative serum PSA levels have been obtained on 226 patients who underwent radical perineal prostatectomy for presumed organ confined prostate cancer (stage T1-2N0M0). Clinical failure as defined by elevation of serum acid phosphatase, biopsy proved local recurrence or evidence of malignant disease on bone scan has occurred in 3.9% of the patients with organ confined, 7.0% with specimen confined and 13.2% with margin positive disease. However, when a PSA elevation of greater than 0.5 ng./ml. was used as an indicator of failure the failure rate became 9.8% for the organ confined group, 39.4% for the specimen confined group and 66.0% for margin positive group. Of the patients who failed clinically the interval from initial elevation of postoperative PSA to clinical detection of failure ranged from 2 to 28 months (median 16). Among the patients with an elevated postoperative PSA level but who have not clinically failed followup ranged from 4 to 46 months (median 23). A total of 11 patients had no evidence of failure at greater than 36 months despite the elevated postoperative serum PSA level. These PSA elevations in patients who undergo supposed curative therapy are distressing. However, at this time the majority of these patients have not failed. In the clinically cured patient biochemical evidence of failure may not be sufficient to change the treatment course.

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 (p0.001). 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).

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.

The records of all testicular cancer patients evaluated and treated at our medical center during two consecutive 9-year periods were reviewed and analyzed for prognostic factors, particularly the impact of cisplatin-based combination chemotherapy. The data base of 244 patients was divided into two eras: 1970–1978, defined as the “pre-cisplatin era” (n=101) and 1979–1987, the “cisplatin era” (n=143). Statistically improved survival (P=0.024) was noted for the 165 nonseminoma patients and for a grouping of 143 patients treated with combination chemotherapy (P=0.004) during the cisplatin era. Stratification by stage revealed that stage II patients had the most significant survival advantage (P=0.001) during the cisplatin era; cancer mortality improved from 48% to 9%. Cancer death rates for stage III patients decreased from 58% to 39% which is clinically but not statistically significant (P=0.497). Stage I patients and the seminoma population did well during both eras, and the impact of cisplatin could not be statistically confirmed in this study for these subgroups. Multivariate statistical analysis confirmed the importance of the era of treatment for the nonseminoma population.

A total of 76 patients (18 with stage A1 and 58 with stage A2 cancer) underwent radical perineal prostatectomy. No perioperative deaths occurred and no patient suffered rectal injury or was incontinent postoperatively. Five patients (3 with stage A1 and 2 with stage A2 disease) had negative surgical specimens, while 6 (4 with stage A1 and 2 with stage A2 cancer) had a single microscopic focus in the radical prostatectomy specimen. Outcome was assessed by first evidence of disease recurrence as a function of the Gleason sum and the local anatomical extent of disease. Of 41 patients 4 (9.7 per cent) with organ-confined disease failed at 2.5, 2.6, 4.3 and 11.9 years. None of 11 patients with specimen-confined disease failed, and 6 of 24 (25 per cent) with positive margins failed at 0.9, 1.2, 2.1, 3.1, 3.2 and 8.0 years. Radiation after an operation for margin-positive disease did not seem to alter the incidence of failure. The distribution frequency of the Gleason sum was noted to shift to a higher total sum as the extent of local disease increased. Kaplan-Meier analysis of the failure rate of patients with organ-confined and organ-nonconfined disease with a Gleason sum of 7 or less versus greater than 7 demonstrated an advantage for those with a sum of 7 or less (p less than or equal to 0.018).

The prognostic significance of disease features recorded at the time of diagnosis was examined among 813 patients with Philadelphia chromosome- positive, nonblastic chronic granulocytic leukemia (CGL) collected from six European and American series. The survival pattern for this population was typical of “good-risk” patients, and median survival was 47 mo. There were multiple interrelationships among different disease features, which led to highly significant correlations with survival for some that had no primary prognostic significance, such as hematocrit. Multivariable regression analysis indicated that spleen size and the percentage of circulating blasts were the most important prognostic indicators. These features, and age, behaved as continuous variables with progressively unfavorable import at higher values. The platelet count did not influence survival significantly at values below 700 X 10(9)/liter but was increasingly unfavorable above this level. Basophils plus eosinophils over 15%, more than 5% marrow blasts, and karyotypic abnormalities in addition to the Ph1 were also significant unfavorable signs. The Cox model, generated with four variables representing percent blasts, spleen size, platelet count, and age, provided a useful representation of risk status in this population, with good fit between predicted and observed survival over more than a twofold survival range. A hazard function derived from half of the patient population successfully segregated the remainder into three groups with significantly different survival patterns. We conclude that it should be possible to identify a lower risk group of patients with a 2-yr survival of 90%, subsequent risk averaging somewhat less than 20%/yr and median survival of 5 yr, an intermediate group, and a high- risk group with a 2-yr survival of 65%, followed by a death rate of about 35%/yr and median survival of 2.5 yr.

Of 244 patients with testis cancer seen between January 1970 and December 1987 (mean followup 70 months) 88 (36.1%) experienced 1 or more early complications (within 1 year), while 16 (6.6%) had a late (greater than 1 year) complication. Chemotherapy-related complications occurred in 55 of 141 patients (39%), including 6 (4.3%) treatment-related deaths. Chemotherapy-related complications were correlated to the initial extent of disease (p equals 0.021) and to more than 4 cycles of cisplatin-based therapy (p equals 0.001). Retroperitoneal lymphadenectomy-related complications occurred in 48 of 148 patients (32.4%) without surgical mortality and were not statistically increased in those performed after chemotherapy. Kidney loss occurred in 6 patients (4.1%) after retroperitoneal lymphadenectomy. Nine of 110 patients (8.2%) treated with radiotherapy experienced an early therapy-related complication, while late complications included 3 gastrointestinal strictures requiring surgical intervention 8 to 10 years after radiotherapy. Only 1 secondary malignancy (other than contralateral testis cancer) was discovered in this review. Initial extent of disease was the best predictor for over-all complication rate and higher over-all complications were noted in the cisplatin era (1979 to 1987) but these associations were not necessarily present for complication rates of individual therapies.