David F. Paulson

Surgical Management and Prognosis of Renal Cell carcinoma Invading the Vena Cava

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 Gerotas 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.

Immediate Adjuvant Chemotherapy versus Observation with Treatment at Relapse in Pathological Stage II Testicular Cancer

Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study comparing two regimens for patients with completely resected pathological Stage II testicular cancer (that is, with positive retroperitoneal lymph nodes). All patients had undergone orchiectomy and dissection of the retroperitoneal lymph nodes. They were randomly assigned to be treated with two cycles of immediate adjuvant cisplatin-based chemotherapy or to be observed monthly with treatment at relapse. The median follow-up period was four years. Of the 97 patients assigned to adjuvant chemotherapy, 6 (6 percent) had a recurrence; however, only 1 had received adjuvant chemotherapy before the recurrence. Three died (one of testicular cancer), and 94 of the 97 survived. Of the 98 patients who were observed, 48 (49 percent) had a relapse. However, almost all patients with relapses were effectively treated, and 93 of the 98 are alive and disease-free; 3 have died of testicular cancer. No identifiable factors were strongly associated with the risk of relapse. We conclude that two courses of cisplatin-based adjuvant chemotherapy will almost always prevent relapse in pathological Stage II testicular cancer treated with orchiectomy and retroperitoneal-lymph-node dissection. However, when surgery, follow-up, and chemotherapy are optimal, observation with chemotherapy only for relapse will lead to equivalent cure rates.

Radical Surgery Versus Radiotherapy for Adenocarcinoma of the Prostate

AbstractThere were 97 patients with clinical stage A2 or B (T1-2N0M0) prostatic adenocarcinoma and normal serum prostatic acid phosphatase levels, negative isotopic bone scans and no pelvic nodal extension as determined by staging pelvic lymphadenectomy assigned randomly to either radical prostatectomy or megavoltage radiation therapy. While 56 patients received radiation, 41 underwent radical prostatectomy. With time to first evidence of treatment failure used as the end point for determination of treatment efficacy, radical prostatectomy was shown to be more effective than megavoltage radiation in establishing disease control.

Radical Prostatectomy for Clinical Stage T1-2N0M0 Prostatic Adenocarcinoma: Long-Term Results

A total of 441 stage T1-2N0M0 and 11 stage T1-2N0M0 cancer patients with an elevated acid phosphatase level only, and 18 stage T1-2N+M0 cancer patients underwent radical prostatectomy. Analysis of the 441 stage T1-2N0M0 cancer patients demonstrated that failure and survival were a function of the disease being organ-confined, specimen-confined or margin-positive, with 10-year failure rates of 12, 30 and 60%, respectively. Of the patients with positive margins 44 were and 79 were not irradiated postoperatively. Postoperative radiation produced no survival advantage. No difference in interval to failure or of survival could be identified between 105 patients whose disease was diagnosed by transurethral resection and 328 who had a palpable abnormality. Eleven patients had negative bone and node findings but they had an elevated acid phosphatase level. All 8 patients not treated with immediate androgen deprivation failed within 36 months.

Impact of Radical Prostatectomy in the Management of Clinically Localized Disease

The cancer specific death rate following radical prostatectomy in patients with organ confined and specimen confined disease was 10% at 13.5 years, less than the noncancer death rate of 20% for patients in these disease extent categories. The median age of all patients in these categories was 65 years. Cancer remains the dominate cause of death in patients with margin-positive disease, being 40% at 13.5 years. Disease detected by prostate specific antigen (PSA) rather than digital rectal examination appears to be of smaller volume and to have a higher probability of negative margins. Data argue that early detection of PSA will shift patients to a more favorable disease category at surgical intervention. Disease recurrence or persistence by PSA detection seems to precede clinical detection of disease by 3 to 5 years. Disease recurrence by PSA detection does not predict survival outcome, probably does not differentiate between local and distant microscopic recurrence, and is not predictive of biological aggressiveness.

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.

PILOT STUDY OF DIETARY FAT RESTRICTION AND FLAXSEED SUPPLEMENTATION IN MEN WITH PROSTATE CANCER BEFORE SURGERY: EXPLORING THE EFFECTS ON HORMONAL LEVELS, PROSTATE-SPECIFIC ANTIGEN, AND HISTOPATHOLOGIC FEATURES

OBJECTIVES Dietary fat and fiber affect hormonal levels and may influence cancer progression. Flaxseed is a rich source of lignan and omega-3 fatty acids and may thwart prostate cancer. The potential effects of flaxseed may be enhanced with concomitant fat restriction. We undertook a pilot study to explore whether a flaxseed-supplemented, fat-restricted diet could affect the biomarkers of prostatic neoplasia. METHODS Twenty-five patients with prostate cancer who were awaiting prostatectomy were instructed on a low-fat (20% of kilocalories or less), flaxseed-supplemented (30 g/day) diet. The baseline and follow-up levels of prostate-specific antigen, testosterone, free androgen index, and total serum cholesterol were determined. The tumors of diet-treated patients were compared with those of historic cases (matched by age, race, prostate-specific antigen level at diagnosis, and biopsy Gleason sum) with respect to apoptosis (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP-biotin nick end-labeling [TUNEL]) and proliferation (MIB-1). RESULTS The average duration on the diet was 34 days (range 21 to 77), during which time significant decreases were observed in total serum cholesterol (201 +/- 39 mg/dL to 174 +/- 42 mg/dL), total testosterone (422 +/- 122 ng/dL to 360 +/- 128 ng/dL), and free androgen index (36.3% +/- 18.9% to 29.3% +/- 16.8%) (all P <0.05). The baseline and follow-up levels of prostate-specific antigen were 8.1 +/- 5.2 ng/mL and 8.5 +/- 7.7 ng/mL, respectively, for the entire sample (P = 0.58); however, among men with Gleason sums of 6 or less (n = 19), the PSA values were 7.1 +/- 3.9 ng/mL and 6.4 +/- 4.1 ng/mL (P = 0.10). The mean proliferation index was 7.4 +/- 7.8 for the historic controls versus 5.0 +/- 4.9 for the diet-treated patients (P = 0.05). The distribution of the apoptotic indexes differed significantly (P = 0.01) between groups, with most historic controls exhibiting TUNEL categorical scores of 0; diet-treated patients largely exhibited scores of 1. Both the proliferation rate and apoptosis were significantly associated with the number of days on the diet (P = 0.049 and P = 0.017, respectively). CONCLUSIONS These pilot data suggest that a flaxseed-supplemented, fat-restricted diet may affect prostate cancer biology and associated biomarkers. Further study is needed to determine the benefit of this dietary regimen as either a complementary or preventive therapy.

Experience with Gleason’s Histopathologic Grading in Prostatic Cancer

The inaccuracy of clinical staging as a predictor of the biologic potential of prostatic cancer has prompted evaluation of additional methods of assessment. We reviewed 228 patients with prostatic adenocarcinoma who presented during a 4-year period. Of the 228 patients 144 with no detectable bony disease underwent staging pelvic lymphadenectomy with or without preliminary bilateral pedal lymphangiography. Histopathologic specimens of the primary diagnostic prostatic biopsy were classified with Gleasons grading system of tumor differentiation. Of the patients with Gleasons sum of 8, 9 or 10, 93 per cent had regional nodal metastases, regardless of preliminary clinical stage. Furthermore, no patient with Gleasons sum of 2, 3 or 4 had nodal metastatic disease. The incidences of falsely positive and falsely negative lymphangiograms were 29 and 35 per cent, respectively, reflecting the unreliability of pedal lymphangiography to predict nodal involvement accurately in patients with prostatic cancer. The Gleason system of histopathologic grading was reliable and reproducible, and afforded an accurate prediction of the surgical stage of disease.

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).