Current Status of Classification and Staging of Prostate Cancer.

The international TNM classification system for prostatic cancer has been recently revised and is most helpful for comparisons between various groups of patients. Today in the United States, the evaluation of certain factors related to clinical and pathologic staging are being further altered. These include primary grade of tumor and the extent and techniques of tumor staging. New tests for acid phosphatase and alkaline phosphatase isozymes are being concurrently evaluated. Advances in the past six years have contributed to further redefinition and subgrouping of previous conventional staging or prognostic assessment of prostatic cancer. Localized (Stage B, C), occult (Stage A), or generalized (Stage D) tumors are being subdivided. Although grade of the primary tumor has been thought to be important only recently has a consensus been achieved by the National Prostatic Cancer Project for a system of assessment that uses cellular patterns and nuclear changes. Aspiration cytology may be a useful adjuvant. The role and type of pelvic lymph node assessment, whether operative, radiographic, or by thin needle percutaneous aspiration, is undergoing additional study. In dealing with the so-called occult (Stage A) lesions, a further subdivision, Stage A,/A2 has been employed. Similar changes in so-called B1 /B2 , C1 /C2 , and D1 /D2 also exist. These are valid attempts to further define extent of disease and overall true tumor burden. Nevertheless, it is still the privilege of the physician to determine the necessity and extent of the use of such classification. Today, the decision to provide therapeutic care based only on a clinical stage must be made with the knowledge of these variations of classification and staging as well as of other developments.

Intraoperative autotransfusion in urologic oncology.

The value of autotransfusion is widely recognized in the surgical community and may be of increasing importance in prevention of acquired immunodeficiency syndrome and hepatitis. The concern of potential contamination of the blood with viable tumor cells has resulted in limited use of autotransfusion in cancer surgery. The objective of this study was to examine the benefits and safety of autotransfusion in patients undergoing major surgery of genitourinary tumors. Autotransfusion was used in 49 consecutive patients. Twenty-four patients had radical cystectomy, ten had radical prostatectomy, 13 had radical nephrectomy, and two had other types of operations. An autotransfusion machine (Haemonetics Cell Saver) was used. The follow-up included physical examination, chest roentgenogram every three months, and bone scan and computed tomographic scan if clinically indicated. Liver and renal profiles were routinely performed every three months. Five of 49 patients developed metastases during follow-up examination from 12 to 23 months. The low incidence of metastatic spread and the pattern of spread fall to implicate autotransfusion as a cause of tumor dissemination. Autotransfusion and predeposited blood banking may result in elimination of or significant reduction in homologous transfusions.

Use of predeposit autologous blood and intraoperative autotransfusion in urologic cancer surgery.

A total of 20 patients underwent major urologic cancer surgery with the combined use of predeposit autologous blood and intraoperative autotransfusion with the Haemonetics Cell Saver. The estimated blood loss ranged from 400 to 2,000 mL (mean 1,208 mL). Total transfusion requirements for the 20 patients were 85.5 units of which 82.5 (96%) were autologous. Predeposit autologous blood accounted for 53 percent, intraoperative autotransfusion blood 43 percent, and homologous blood 4 percent of the total transfusion requirements. Of the 20 patients in the study, only 1 received homologous blood. There were no complications related to either modality of autotransfusion. Our data suggest that using the combined modalities of predeposit autologous blood donation and intraoperative autotransfusion, major urologic cancer surgery can be performed without homologous blood in most cases.

Transitional cell carcinoma of ileal loop following cystectomy.

This is the second case reported in the literature involving transitional cell carcinoma in an ileal loop. The case is described and the literature reviewed.

Bladder wall fibrosis following intravesical mitomycin treatment for superficial bladder cancer.

Mitomycin is used extensively for the prevention of recurrence of superficial bladder cancer. Most treatment regimens of mitomycin are long term, since this seems more effective in preventing recurrence. During treatment some patients develop cystitis of variable severity, which may lead to mucosal ulcerations and cessation of treatment. We report a case in which long-term treatment with mitomycin, following a single episode of transitional cell bladder cancer, has led to bladder fibrosis and loss of its function, without evidence of tumor recurrence.

Preliminary reticulum cell sarcoma of prostate gland.

A case of primary reticulum cell sarcoma of the prostate gland is presented. This is the seventh well-documented case we have found in the literature. No evidence of extraprostatic extension has been found two and a half years after diagnosis was made, despite no chemotherapy nor radiotherapy.

Insulin-induced growth hormone responses in patients with prostatic carcinoma.

Insulin-induced pituitary growth hormone (GH) response was studied in 12 patients with prostatic carcinoma. Three patients demonstrated significant abnormal GH release associated with concentrations which remained on a high plateau during the study. The patients subsequently presented clinically with rapidly progressing disease. Such observations are compatible with the viewpoint that abnormally high or low GH levels systemically present, may be associated with a particularly bad clinical prognosis. Further studies will clarify this relationship.

Further study of fibrinogen degradation products in bladder cancer detection.

A new, rapid immunoassay kit for assaying fibrinogen degradation products (FDP) was studied in 56 patients with cancer of the bladder and in 48 control patients. The specificity of the kit was demonstrated with a small number of false positive results. In bladder cancer patients with low-stage, small superficial tumors, FDP was positive in 32.2 per cent. The combination of urinary cytologic examination with FDP increased the accuracy of the positive results to 80 per cent. The rapid FDP test supplements the urinary cytology in the follow-up and detection of early bladder cancer.

Estramustine phosphate with multiple cytotoxic agents in treatment of advanced prostatic cancer.

Twenty-five patients with histologically proved adenocarcinoma of the prostate were divided into two groups and submitted to combination therapy with estramustine (Estracyt), cyclophosphamide (Cytoxan), 5-fluorouracil, and Cisplatin. Group A consisted of 10 patients newly diagnosed Stage D disease with no prior treatment. Group B consisted of 15 Stage D patients who had become hormonally unresponsive. Group A patients demonstrated an initial 100 per cent response rate including 70 per cent partial objective responses and 30 per cent stabilizations. Group B patients had a 46 per cent response with 39 per cent complete and partial responses and 6 per cent as stabilized. Toxicity was tolerable judged by the NPCP criteria. Both groups of patients are still under study for up to two years to determine if this therapy is superior to other traditional therapies.

Bladder-sparing multimodality treatment of muscle-invasive bladder cancer: a five-year follow-up.

OBJECTIVES: To determine the long-term results of a bladder-sparing approach in the treatment of muscle-invasive bladder cancer. METHODS: Ninety-four patients with invasive transitional cell carcinoma of the bladder were treated by transurethral resection followed by 2 or 3 cycles of cisplatin-based chemotherapy. Patients were then treated with 6480 cGy of radiation in 49 patients, segmental cystectomy in 8, or surveillance only in 7. Patients who failed to respond to chemotherapy or radiation therapy, or who developed recurrent muscle-invasive disease in follow-up, underwent salvage cystectomy. Patients were then carefully followed for a median follow-up of more than 5 years. RESULTS: After initial therapy, 53 patients (56%) were alive with their bladder preserved. Thirty of those 53 (57%) developed a local recurrence in follow-up. After a median follow-up of more than 5 years, the ultimate relapse-free survival is 49% (Stage T2, 84%; T3, 53%; and T4, 11%; P < 0.01). Of all patients enrolled, 53% had bladder preservation; however, of the currently surviving patients, 16 of 39 (41%) have their bladders intact (T2, 50%; T3, 37%; T4, 0%). Only 18% of the initially enrolled population is alive with a preserved bladder. The 5-year survival of patients who had cystectomy at some point during the study, compared with those who have had their bladders preserved, was 65% versus 40%, respectively (P < 0.01). CONCLUSIONS: Our long-term results with multimodality therapy with attempted bladder preservation showed no definitive improvement in survival compared with modern series of cystectomy alone, and a disappointingly low rate of disease-free bladder preservation. We found a high rate of locally recurrent disease in the preserved bladders. We also noted a decrease in survival in our patients with bladder preservation compared with those without preservation. Bladder preservation, although possible, should be limited to a very select group of patients.

Neuroblastoma presenting as renal cell carcinoma in an adult.

A rare case of a fifty-six-year-old female with neuroblastoma is presented. Possible implications as to etiology are discussed, and the radiographic similarities between renal cell carcinoma and neuroblastoma are presented.

Paradoxical increase of renal blood flow in anesthetized hypertensive dog treated with indomethacin.

To evaluate the effect of prostaglandin inhibition on the renal blood flow of the ischemic kidney, we administered indomethacin to 10 anesthetized dogs with renal artery stenosis and contralateral nephrectomy. Following the operation to produce renal ischemia, there was an increase of blood pressure associated with an increase of renin and the prostaglandins F1 (PGF1), and E (PGE). The administration of indomethacin to the intact, normotensive animals caused the anticipated decrease of prostaglandin E, renin, and renal blood flow. However, in the hypertensive dogs, indomethacin caused a paradoxical 45 per cent increase in the renal blood flow, despite a 44 per cent decrease of prostaglandin E. PGF1, PGE, renin, and erythropoietin exhibited the anticipated decreased levels. The study suggests that prostaglandins may not be the sole important factor in the regulation of renal blood flow in the presence of ischemia. Other important factors likely include the renin-sensitive angiotensin, the adrenergic, and the kallikrein-kinin systems.

Sisomicin in urinary tract infection: Tolerance and efficacy study.

Twenty-one patients with gram-negative urinary tract infections were treated with sisomicin, a new aminoglycoside antibiotic. Bacteriologic cure was achieved in 62 per cent of patients, and improvement in another 33 per cent. Mild transient elevation of serum creatinine occurred in 3 patients. No other toxicity was observed. Further clinical trials with more frequent dose administration and in combination with other antibiotics is suggested.

Nonhormonal chemotherapy for disseminated renal cell carcinoma.

Twenty-five patients with disseminated renal cell carcinoma have been followed for eleven months. These patients have been treated with CCNU, bleomycin, methotrexate, and platinum in various combinations. The results have been discussed in light of other studies using chemotherapeutic agents against this disease process.

Relationship of prior hormonal therapy to subsequent estramustine phosphate treatment in advanced prostatic cancer.

The relationship of prior hormonal therapy to subsequent response on estramustine phosphate (Estracyt) was examined in 107 patients with advanced prostatic cancer treated in two different Phase II chemotherapy trials. In both trials patients with the longest prior hormonal treatment were the least likely to respond to estramustine phosphate. Patients in the series from the National Prostatic Cancer Project with a response classification to prior hormonal therapy had only a 26 per cent response to subsequent estramustine phosphate therapy, whereas 40 per cent of those with no prior response to hormonal therapy responded to estramustine phosphate. This latter group had the shortest average disease duration from diagnosis. The sample of prostate cancers studied appeared to include groups that were sensitive to both hormones and cytotoxic activity as well as to either of these two alone. These data support the contention that estramustine phosphate may act both as an estrogenic and a cytotoxic agent.

Two new, direct, and specific methods of acid phosphatase determination. National field trial.

A national study of the new specific assays for prostatic acid phosphatase was conducted by the National Prostatic Cancer Project. The results of the study have confirmed that the counterimmunoelectrophoretic method is easily reproducible, highly specific, and sufficiently sensitive. Based on tests as performed by different institutions, the counterimmunoelectrophoretic (CIEP) method was also shown to have high reproducibility and was found to be of much greater sensitivity than the conventional biochemical methods for the detection of earlier stages of prostatic cancer. The national study of the radioimmunoassay (RIA) has shown that although being a highly sensitive method, it could not be readily distributed at this time from one specialized center. It requires highly specific, expensive technical assistance and is not yet available nationwide. CIEP is recommended at this time to be used as the preferred method in the evaluation and diagnosis of prostatic cancer. The value of counterimmunoelectrophoresis in detecting early prostatic cancer as a screening method is promising, but still under study.

Fine-needle aspiration of metastatic lesions and regional lymph nodes in genitourinary cancer.

A percutaneous fine-needle aspiration biopsy of metastatic tumor and/or retroperitoneal, pelvic, or abdominal lymph nodes was accomplished in 101 patients. A diagnosis of metastatic disease was confirmed by this method in 49 patients. In 26 patients, surgical excisional biopsy or exploratory laparotomy was avoided. An unknown pelvic mass causation was diagnosed in 3 patients. In 15 of 57 patients with localized bladder, prostate, or testis cancer, involvement of regional lymph nodes was confirmed by transabdominal find-needle aspiration. All 57 transabdominal aspirations were performed without complications. The method is inexpensive, safe, and can have a high accuracy in diagnosing a local tumor spread or distant metastases.

High-dose tamoxifen in metastatic renal cell carcinoma.

The effectiveness of high-dose Tamoxifen in the treatment of metastatic renal cell carcinoma was evaluated. Fifteen patients were treated for eight weeks with 80 mg of Tamoxifen daily. Side effect were minimal. Results showed progression of disease in 47 per cent of the patients, no change in disease was seen in 40 per cent, and 13 per cent showed a partial objective response. Twenty per cent of patients showed deterioration of performance status. High-dose Tamoxifen does not appear to be useful in the treatment of advanced renal cell carcinoma.

Intravesical bacillus Calmette-Guerin for patients with high-risk superficial bladder cancer.

Intravesical bacillus Calmette-Guérin (BCG) was employed in the treatment of 55 patients with aggressive superficial transitional cell carcinoma of the bladder (cTa, cT1, cTis). All of the patients had a previous history of recurrent superficial disease, and 41 (75%) were treatment failures following other intravesical therapy. Thirty-six (66%) patients responded to treatment, and 19 (34%) were treatment failures. Twenty-seven (66%) of 41 patients with cTa-cT1 tumors and 9 (64%) of 14 patients with cTis responded, with a mean follow-up period of 30.5 months. Disease progression was noted in 8 (15%) of the patients and muscle invasive disease in 6. Patients with a history of three or more previous events of tumor recurrence, positive urinary cytology, and multicentric disease, all fared worse than patients without these characteristics (p less than 0.05). BCG is an effective agent in controlling superficial transitional cell carcinoma of the bladder, even in a high-risk group of patients who failed previous intravesical therapy. BCG should be employed in this group of patients prior to radical surgery.

Neoadjuvant hormonal therapy and radical prostatectomy in the treatment of clinical stage T3 cancer of the prostate.

We evaluated the results of a treatment protocol that consisted of neoadjuvant hormonal therapy followed by radical retropubic prostatectomy (RRP) for clinical stage T3 (cT3) prostate cancer. Sixty-six patients with cT3 prostate cancer underwent staging procedures that included metastatic work-up and evaluation under anesthesia. Neoadjuvant hormonal treatment was given for 3 to 6 months, followed by re-evaluation under anesthesia. Patients considered to have a resectable prostate following neoadjuvant treatment underwent operation. Disease-free survival [prostate-specific antigen (PSA) < 0.1 ng/ml] was calculated by the Kaplan-Meier method for cT3 patients and for a group of patients with clinical stage 1 and 2 disease (cT1-2), who underwent RRP without neoadjuvant hormonal therapy. Patients with pT3 disease in both groups received early adjuvant radiation treatment. Patients in the cT3 group who were not clinically downstaged were treated with radiation. Patients with positive lymph nodes continued hormonal therapy. The pretreatment PSA for the cT3 group was 43.6 ± 55.6 ng/ml, and 10.64 ± 7.18 ng/ml for the cT1-2 group (p < 0.05). Of 66 cT3 patients, 53 (80%) were clinically downstaged and operated on and 47 (71%) underwent RRP. At 36 months, there was no significant difference in the PSA relapse rate between these two groups; both had significantly lower rates than did patients in the cT3 without RRP. At 48 months, 79% (21 patients) of the patients in the cT3-RRP group were disease free compared with 50% of those in the cT3 without RRP (4 patients). Neoadjuvant hormonal therapy for stage cT3 prostate cancer selects patients whose cancer can be controlled by RRP for an extended period of time.