NCCN Practice Guidelines for Prostate Cancer.

Systemic therapies for prostate cancer are likely to improve, and as they do, they will have enormous impact on the treatment of high-risk and locally advanced cancers. Further technical improvements in radiotherapy and alternative local modalities, such as cryoablation, are also likely, and will bring even more options for local control. It is certain these guidelines will continue to evolve.

Cryosurgical ablation of the prostate.

Cryosurgery for the treatment of prostatic disease, a technique that originated in the mid-1960s and was almost abandoned in the mid-1970s, has re-emerged in the 1990s for the treatment of cancer of the prostate. This renewed interest is due to several factors, including the development of intraoperative ultrasound, the refinement of percutaneous access techniques, and improvements in cryosurgical apparatus. The modern technique features the transperineal percutaneous placement of several (generally five or six) metal probes, each 3 mm in diameter, in the prostate under ultrasound guidance. After insertion, the probes are cooled in a manner that produces complete freezing of the prostate and, if required, extraprostatic extensions of disease. The freezing process is monitored by ultrasound, which provides an image of the boundary of freezing as it advances through the prostate and thereby provides control of the extent of freezing. This review describes the historical background of prostatic cryosurgery and the current status of this new procedure, including the important issues of case selection, technique, and results. The recent nature of this experience precludes judgment of long-term merit, but the favorable short-term results of cryosurgical ablation of the prostate encourage further selective use of this technique in the treatment of prostate cancer. Definition of appropriate patient selection and optimal technique are needed to improve treatment by cryosurgery.

If you 'watch and wait,' prostate cancer may progress dramatically.

PURPOSE: Observation has been proposed as an option for localized prostate cancer. However, most series reporting on 'watch and wait' include patients treated by TUR or hormones that may affect results. We retrospectively reviewed the natural history of truly untreated prostate cancer and report the outcome for these patients. METHODS AND MATERIALS: From 1976 to 1992, 34 patients of median age 70 years (range 56-88) with biopsy proven localized adenocarcinoma of the prostate refused therapy. All had negative bone scan and none underwent TUR or hormone treatment. No patient was lost to follow-up (median 76 months). Failure patterns and survival were analyzed. RESULTS: At diagnosis 27 patients had palpable nodules (T2), of which 13 were well differentiated and 14 moderately differentiated. Seven had moderately differentiated T3 lesions. Mild prostatitis including nocturia, hesistancy, and urgency were reported in 16 T2 and 6 T3 patients. Within 36 months, local progression requiring therapy occurred in all T3, all T2 moderate and 5 of 13 T2 well-differentiated patients. Systemic progression occurred in 6 of 7 T3, 9 of 14 T2 (mod), and 2 of 13 T2 (well) patients. Overall 59% are alive, 26% succumbed to prostate carcinoma and 15% to other causes. CONCLUSION: Observation results in a high rate of local progression requiring intervention (77%) and excessive systemic disease development (50%) for patients with clinically palpable disease. Perhaps this strategy is viable for earlier stage lesions detected by PSA but it must be tested in a rigorous fashion before accepted.

Translational studies of glutathione in bladder cancer cell lines and human specimens.

Glutathione (GSH) levels were measured in 13 human tumor cell lines derived from carcinomas of the bladder, ovary, and colon and from melanoma and glioblastoma. High levels were found in four of five bladder cell lines. The average GSH concentration in the bladder cell lines was approximately 6-fold higher than in the non-bladder cell lines. Because this difference suggested the possibility of elevation of GSH in urothelial neoplasia, we measured GSH in bladder tumor tissue from patients with transitional cell carcinoma (TCC) of the bladder (Group I, n = 17). GSH was also measured in two types of control tissues: (a) nontumor bladder tissue from patients with TCC or a history of TCC of the bladder (Group II, n = 23); and (b) bladder tissue from patients without bladder cancer (Group III, n = 14). Thirteen sets of paired specimens of tumor and nontumor bladder tissue from the same patient were evaluated. The tissues were flash-frozen, and GSH was measured after histological assessment of the same samples. Free and total GSH (free + mixed disulfides) were measured by a high-performance liquid chromatography assay with fluorescence detection and expressed as nanomoles/mg protein. The mean free GSH (+/- SD) for groups I, II, and III was 32.0 +/-18.7, 17.3 +/- 11.4, and 9.3 +/- 4.0, respectively, and the mean total GSH was 45.9 +/- 32.5, 23.7 +/- 17.1, and 12.2 +/- 6.7. The respective differences between groups (I and II, I and III, and II and III) were statistically significant for both free and total GSH (Ps ranging from <0.0001 to

Pathology and its importance in evaluating outcome in patients with superficial bladder cancer.

Subtle cytologic and histologic nuances have a major impact on diagnosis and, consequently, on therapy for superficial bladder cancer. Therefore, the urologist and the pathologist must carefully assess all clinical findings before a course of treatment can be determined. The urologist must advise the pathologist of all the circumstances surrounding a biopsy--whether its purpose is for preliminary clinical impression or diagnosis, the patient's recent treatment history, the availability of previous biopsy specimens for comparison, a thorough history of treatments that may induce characteristic cytologic changes that might lead to misdiagnosis, and alternate diagnostic possibilities drawn from initial pathology and treatment history. Armed with this information, the task of the pathologist is to provide as much data as possible regarding tumor histopathology from the biopsy specimens. Thus, establishment of a close working relationship between the urologist and the pathologist is an important tool for (1) initially characterizing superficial bladder cancer, which is essential in determining an appropriate course of treatment, and (2) accurately evaluating follow-up biopsies to determine the effectiveness of that treatment.

Intravesical chemotherapy versus immunotherapy for superficial bladder cancer.

The decision to treat superficial bladder cancer with intravesical therapy should be predicated primarily on disease stage and grade as well as the patient's clinical history. Once the decision to proceed with intravesical therapy has been made, the clinician must select the appropriate agent. Several agents are available and the choice of which agent to use should be based on careful consideration of the potential benefit of a given drug versus its inherent risk of complications. The first drug to be administered intravesically, thiotepa is an alkylating agent used as first-line treatment for low-grade lesions; it has limited use against higher-grade tumors or carcinoma in situ. In addition, the low molecular weight of thiotepa results in significant systemic absorption, which often results in myelosuppression. Mitomycin, also an alkylating agent, has shown significant activity as both first-line therapy and in patients with recurrent disease. Unlike thiotepa, mitomycin has a relatively high molecular weight, and the incidence of significant bladder absorption and systemic side effects is low. Doxorubicin, which also possesses a high molecular weight, is used intravesically against superficial bladder cancer more frequently in Europe and Japan than in the United States. Immunotherapy with bacille Calmette-Guérin is the treatment of choice for carcinoma in situ and high-grade T1 lesions. It is associated with the highest incidence of both minor and major adverse reactions, however, and its use should be tempered by its potential toxicity.

Primary renal sarcoma.

Primary renal sarcoma represents approximately 1 per cent of all primary tumors of the kidney. The purpose of this study is to review the experience at Roswell Park Cancer Institute with the treatment of primary renal sarcoma. Four patients with a diagnosis of primary renal sarcoma admitted from 1976 to 1983 form the basis of this review. All patients underwent radical nephrectomy. The tumor was localized in two patients, and locally invasive in two patients. All patients had recurrence of metastatic disease. Patients with localized disease recurred at 19.0 and 25.0 months respectively. Patients with invasive disease recurred at 4.0 and 5.0 months respectively. Patients presenting with localized disease survived a mean of 34.0 months. Patients presenting with invasive disease died at 6.0 and 10.0 months from time of diagnosis. Primary renal sarcoma is a rare entity. Only patients presenting with localized disease have a reasonable chance for prolonged survival.

Management of bladder cancer.

Bladder cancer is a paradigm of malignancy, representing the spectrum from localized to metastatic disease, and manifesting varied histologic types, including transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma. Preclinical and clinical data suggest that a common stem cell of origin gives rise to the different histologic types and that these patterns are of clonal origin. Localized bladder cancer is managed optimally by transurethral resection, with or without adjuvant intravesical chemotherapy. Invasive cancer or relapsed superficial disease may require more radical surgery or radical radiotherapy. In recent years, the evolution of techniques of continent urinary diversion or of bladder replacement has revolutionized the management of invasive disease. However, the 5-year survival for invasive bladder cancer is still approximately 50%, and innovative strategies have been developed, combining definitive local treatment and systemic chemotherapy, in an attempt to improve survival. For patients with metastatic disease, the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (the MVAC regimen) has achieved response rates as high as 70% but with a median survival of only 12 months. Until cure rates are improved, one of the hallmarks of effective management of metastatic disease will remain the provision of thorough and well-structured palliative treatment programs. Recently, the introduction of new agents (such as paclitaxel, gallium, ifosfamide, and gemcitabine) has led to promising response rates, and further clinical trials of these agents alone and in combination are in progress. In addition, an improved understanding of the mechanisms of resistance to treatment, including the implications of the expression of p-glycoprotein, p53 proteins, and other biochemical predictors of outcome, and of strategies to overcome such resistance, may lead to more effective management of advanced disease. Furthermore, real progress will be made only through the application of well-designed clinical trials to test the efficacy and toxicity of the new strategies of treatment.

Reported family history of cancer in 1,271 prostate cancer cases and 1,909 controls.

Prostate cancer risk has been associated with a family history of the disease. A two- to three-fold increase in risk has been observed in several studies. Details concerning modification of this risk by age, type of familial history of prostate cancer, and possible involvement of history of cancer at other sites have been less well documented. This case-control study of 1,271 prostate cancer patients and 1,909 control subjects admitted to Roswell Park Cancer Institute in Buffalo, NY, found age-adjusted increased risk associated with reporting a history of prostate cancer in a father (RR = 2.3, 95% Cl 1.4-3.3) or brother (RR = 2.5, 95% Cl 1.6-3.9). Subjects with both a father and brother affected had a 6.5-fold (95% Cl 1.4-30.5) increased risk of prostate cancer. Greater risk were observed at younger ages of diagnosis. Risks associated with reporting a father or a brother affected were not significantly elevated for patients over age 70 at diagnosis. No significant differences in patients reporting histories of cancer other than prostate cancer were observed regardless of relationship, age at diagnosis, or type of cancer examined. These observations from a large cancer patient population may be useful when making recommendations for cost-effective prostate cancer screening and for directing investigators to the potentially most informative subjects.

A comparison of prostate cancer patients in Japan and the USA.

Clinical characteristics of prostate cancer patients were analyzed to compare the rates of progression of prostate cancer between patients in Japan (Gunma Urological Oncology Study Group: GUOSG) and the USA (Roswell Park Cancer Institute: RPCI), between 1980 and 1989. The stage of disease was more advanced and the age was greater in GUOSG patients compared with RPCI patients. However, the prostate cancer death rate of stage D patients at RPCI was significantly higher than that of the GUOSG. Moreover, the survival rate of stage A patients in the GUOSG was better than that of RPCI patients. The possibility of biases which may affect both the clinical characteristics and survival rates in the 2 populations studied is discussed. To determine whether there is a real difference in the rate of prostate cancer growth between the 2 countries will require a prospective study, ideally conducted in large population groups.

Staging and grading in the survival of adrenal carcinomas.

In 53 patients with histologically proven adrenal cortical carcinomas the most common metastatic sites, at the time of diagnosis, were the liver, lymph nodes, bone and lungs, and during the course of the disease, the lungs. At the time of diagnosis six (11%) of our patients were in Stage S1, seven (13%) in S2, 11 (21%) in S3 and 29 (55%) in S4. Histologic grading (G) in 43 patients showed G1 grade in 11 (26%), G2 in seven (16%) and G3 in 25 patients (58%). Median survival in months (estimated 5-year survival rate) for the various stages were: S1 46 (33%), S2 84 (57%), S3 eight (18%) and S4 seven (7% at 2 years) (P = 0.01). Median survival in months (estimated 5-year survival rate) for the various grades were: G1 46 (46%), G2 24 (43%), G3 five (4% at 2 years) (P = 0.003). In this series, tumor stage (P = 0.01) and grade (P = 0.003) were predictors of survival and the two were closely correlated (P = 0.02).

Effect of perioperative chemoimmunotherapy with cyclophosphamide and autologous tumor vaccine in murine MBT-2 bladder cancer.

The in vitro cytotoxic activity of splenocytes from C3H/He mice implanted subcutaneously with 10(6) syngeneic MBT-2 tumor cells on day 0 was significantly enhanced after cyclophosphamide (100 mg./kg., intraperitoneally) given 2 days before tumor resection on day 17, with or without active specific immunization with BCG plus autologous irradiated tumor cells (vaccine) 1 week after tumor resection. Furthermore, a significantly lower tumor incidence was seen in mice challenged with 10(5), but not 10(6), tumor cells per mouse 24 hours after tumor resection on day 17 and treated with cyclophosphamide on day 15 and postoperatively with vaccine than was found in nontreated tumor resected mice. Phenotypic analysis of cells from spleen showed that cyclophosphamide pretreatment and postoperative vaccine, either singly or in combination, induced a significant increase of both CD44+ memory T cells and CD11b+ myeloid/macrophage cells. Thus, in addition to a specific antitumor immune response, a nonspecific cytolytic mechanism may also play a role in the observed antitumor effect.

Adrenal adenocarcinoma: a review of 53 cases.

PROBLEM: Fifty-three patients (30 men, 23 women) with histologically proven adrenal carcinoma were reviewed. Nineteen (36%) had endocrine manifestations from functioning tumors. Arteriography was positive in 95% (19/20), CT scan in 94% (17/18), and ultrasound in 92% (12/13). Seventy-six percent of the patients, at the time of diagnosis, were stage III and IV. Most common metastatic sites were the liver, lymph nodes, bone, and lungs. Local recurrence developed in 39% of cases (15/38). METHOD: Forty-one patients underwent an operation. Complete surgical removal of all gross tumor was achieved in 24 patients. RESULT: The overall median survival time was 8 months, and the estimated 5-year survival rate 19%. There were significant differences in survival between the various stages (P = 0.01) and between the group of patients who underwent complete excision of the tumor and those with incomplete resection (P = 0.002). CONCLUSIONS: Complete surgical excision offers the best prospect for long-term survival in localized adrenal carcinoma.

The combined-action of ici-d1694, 5-fluoro-2'-deoxyuridine and 5-Fluorouracil in inhibiting the growth of a human renal-cell carcinoma cell-line (rpmi-se) in-vitro.

In order to investigate possible interactions among ICI-D1694 (a new folate-analog thymidylate synthase inhibitor), 5-fluoro-2'-deoxyuridine (FdUrd) and 5-fluorouracil (FUra), the effect of these agents alone and in 2-drug combinations against a human renal cell carcinoma cell line (RPMI-SE) in vitro was investigated. The median IC50's for cell growth inhibition for ICI-D1694, FdUrd and FUra were 4.00, 7.23 and 1,340 nM, respectively. To quantitatively assess the degree of agent-combined action for 2-agent combinations of the 3 drugs, data from combination experiments were fitted with a response surface mathematical model (Greco et al, Cancer Res 50: 5318-5327, 1990). In 3 experiments for each combination, moderate Loewe synergism was consistently shown for ICI-D1694/FdUrd, less prominent Loewe synergism was indicated for FdUrd/FUra; and Loewe additivity was shown for ICI-D1694/FUra. Studies in vitro to elucidate the mechanism of the interaction of ICI-D1694 + FdURD, and in vivo to establish possible therapeutic advantages are warranted.

A new approach in the diagnosis and follow-up of bladder cancer. FISH analysis of urine, bladder washings, and tumors.

The aim of the present study was to ascertain whether fluorescence in situ hybridization (FISH) of urine could be a useful approach in bladder cancer. Herein, we present the cytogenetic and FISH findings in patients with and without bladder cancer. The samples examined with FISH consisted of urine, bladder washings, and tumor tissue, when available. The results obtained show that the FISH technique, particularly when used on urine, is a very useful tool in the diagnosis, early detection, and management of bladder cancer.

Salvage surgery for radiation failure in prostate cancer.

METHODS: Salvage surgery was done in 43 patients who did not respond to radiation therapy of prostate cancer between 1982-1991. Thirty-five patients underwent salvage prostatectomy and 8, cystoprostatectomy. RESULTS: The complications were significant; four patients had rectal injuries (all closed primarily), one had a ureteral injury, and there was one perioperative death. Urinary incontinence occurred in 10 of 35 patients (30%). Pathologic step sections of the prostate showed that only 13 of 43 patients (30%) had negative surgical margins. Follow-up (range, 1-10 years) revealed that 34 patients were alive, and 9 had died. Eleven of 20 patients were alive who were followed more than 5 years. Ten patients were considered to have no evidence of disease (undetectable prostate specific antigen levels). CONCLUSION: In selected patients, salvage surgery has a place in the treatment of prostate cancer after radiation therapy failure.

Prognostic factors in survival of bladder cancer.

Clinical and pathologic data of 36 patients with transitional cell carcinoma of the bladder were investigated to determine the significance on patient survival of these factors: pathologic grade and stage; the immunohistochemistry of eight cell and tumor markers; nuclear DNA flow cytometric parameters; and patient smoking status. The bivariate and multivariate statistical analysis significantly correlated patient survival rates with the immunohistochemical expression of blood group, isoantigens A (P less than 0.05), O(H) (P = 0.001), the oncogene-related protein ORP-p21 (P less than 0.05), the pathologic grade and stage (P = 0.002), and the tumor DNA ploidy (P less than 0.05). Smoking status correlated aneuploidy (P less than 0.05) and tumor expression of ORP-p21 (P less than 0.05) with the patient survival rate. Despite the relatively small number of patients in this study, the results suggest that the clinicopathologic variables are significant factors in survival of bladder cancer.

[Antibiotic therapy in ambulatory surgery]. / Zur Antibiotikatherapie in der ambulanten Chirurgie.

Antibiotic therapy in outpatient surgical care is reviewed. In the first section some skin and soft-tissue infections are discussed, where antibiotics are likely to achieve clinical cure. In the second section we examine, where surgical treatment alone is essential for successful eradication of the infection. Wound management, where antibiotics are still controversial, is mentioned in the last section. Some pharmacological data on the discussed antibiotics are given.