Extended sector biopsy for detection of carcinoma of the prostate.

Purpose: To determine whether an extended sector biopsy of the prostate will increase the detection of prostate cancer, without causing an increase in morbidity. Materials and Methods: A total of 74 men with a mean age of 62.3 years (46-98 years) who either had an elevated PSA or an abnormal digital rectal exam underwent a transrectal ultrasound guided needle biopsy. Beginning on 7/1/98, an extended sector biopsy technique was performed on 74 patients by one urologist (RRB). Each transrectal ultrasound guided needle biopsy included 12 total cores (normal sextant biopsy, 2 in each peripheral zone, and 2 in the transition zone). We retrospectively reviewed the biopsy results for the location of cancer. PSA data and morbidity of the procedures were reviewed. Results: Of 74 total patients, 40 (54.1%) were positive for adenocarcinoma of the prostate. There were 10 positive results detected only in the additional zones. If one looks at the total number of cancers detected (40), then 10/40 (25%) of the cancers detected were found in the additional regions only or in 13.5% of all patients biopsied. Of the 10 patients with sector only prostate cancer, 8 were detected in the peripheral zone, 1 in the transition zone and 1 in both zones. All 10 patients had a Gleason pattern score 3+3=6 or 4+3=7. There were no atypical or PIN cores found in the sector zones only. PSA ranged from 1.2-142 (median 6.0 ng/ml). The median PSA was 6.2 ng/ml in all patients found to have cancer, and 6.0 ng/ml in the cancers detected only in the additional zones. There was 1 (1.4%) complication of urinary retention and fever. Conclusion: Our study suggests that an extensive sector biopsy may increase the detection of prostate cancer by 13.5% over a routine sextant biopsy, without demonstrable serious morbidity.

Carcinosarcoma of the urinary bladder--an aggressive tumor with diverse histogenesis. A clinicopathologic study of 4 cases and review of the literature.

OBJECTIVE: Carcinosarcomas of urinary bladder are rare malignant neoplasms. Seventy-eight cases have been previously described. The histologic composition of these tumors is variable, but diagnosis requires the presence of both epithelial and mesenchymal malignant components. We report 4 additional cases, with an emphasis on unusual histologic features. METHODS: Histologic and immunohistochemical examinations were performed on bladder tumors from 4 patients. Clinicopathologic features of previously reported and current cases were reviewed and summarized. RESULTS: Four patients (3 men, 1 woman) age 54 to 77 years were found to have polypoid masses in the urinary bladder. In all cases, histologic examination showed biphasic neoplasms with distinct mesenchymal and epithelial components. The morphologic and immunohistochemical characteristics of the tumors varied. One of the cases was remarkable for the presence of liposarcoma, malignant peripheral nerve sheath tumor, and micropapillary urothelial carcinoma. Two of the patients died 2 years after diagnosis, which is consistent with the previously reported aggressive nature of urinary bladder carcinosarcomas. CONCLUSIONS: Carcinosarcomas of the urinary bladder are rare, aggressive malignant neoplasms. To our knowledge, a liposarcomatous component has been reported in only 1 case previously, and components of micropapillary urothelial carcinoma and malignant peripheral nerve sheath tumor have not been reported previously in carcinosarcomas of the urinary bladder. Because of the aggressive biologic behavior of these tumors, they should be identified promptly and treated appropriately.

Interferons and bladder cancer.

With the introduction of BCG, intravesical instillation of immunotherapeutic agents has become a mainstay of therapy in the treatment of superficial bladder cancer. Interferon is capable of inducing a non-specific cellular and humoral immune response towards tumor cells. It has shown promise in reducing the recurrence and progression rates of superficial bladder cancer. In contrast to BCG, intravesical interferon is associated with minimal side effects and a very low dropout rate. Current research has focused on the use of interferon in combination with immunotherapeutic and cytotoxic drugs.

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.

Charge and length of hospital stay analysis of radical retropubic prostatectomy and transperineal prostate brachytherapy.

PURPOSE: For the treatment of clinically localized prostate cancer radical retropubic prostatectomy with its attendant hospital stay should be associated with higher charges than transperineal prostate brachytherapy. We report a comparative case series to determine patient charges and length of hospitalization of 2 modalities of monotherapy for localized prostate cancer. MATERIALS AND METHODS: A total of 35 consecutive patients with clinically localized prostate cancer underwent radical retropubic prostatectomy (16) or transperineal prostate brachytherapy (19) at the Arthur James Cancer Hospital and Research Institute. Complete charge and length of hospital stay data were collected for each patient. Total charges were calculated and the 2 modalities were compared. RESULTS: Charge data were available in 33 cases. Average total charges in the prostatectomy and brachytherapy groups were $15,097 and $21,025, respectively ($5,928 difference, p <0.0001). The difference increased further when outliers were excluded from study. Average length of hospital stay and average charge in the prostatectomy group were 3.8 days and $1,897. The higher charges for transperineal prostatic brachytherapy were due to dosimetry calculations, radioactive seeds and seed implantation. CONCLUSIONS: At our institution the average total charges for transperineal prostate brachytherapy are significantly higher than those for radical retropubic prostatectomy.

Seminal vesicle cystadenoma: a case report and literature review.

Primary tumors of the seminal vesicle are rare; most reported cases are carcinomas, with occasional reports of primary seminal vesicle sarcoma and an uncommon group of mixed epithelial-stromal tumors. The latter have been variably reported in the literature as cystadenoma, phyllodes tumor, and mullerian adenosarcoma-like tumor. We describe a 37-year-old man who presented with symptoms of bladder outlet obstruction and was found to have a pelvic mass. Resection of the mass yielded a biphasic tumor characterized by cystically dilated glandular spaces admixed with spindle-shaped stromal cells. There was no significant cytologic atypia or mitotic activity. The histologic features are most consistent with the reported cases of cystadenoma. The patient is alive, with no evidence of disease, 6 months after surgery. This case adds to the gradually growing body of literature on mixed epithelial-stromal tumors of the seminal vesicle.

Perineural invasion in transitional cell carcinoma and the effect on prognosis following radical cystectomy.

OBJECTIVES: The relationship between perineural invasion and prognosis has been demonstrated to be poor in a number of malignancies. This has not been evaluated in the bladder. We performed a study to determine the occurrence of nodal metastases, extranodal metastases, and disease-free survival in patients with perineural invasion (PNI) and/or angiolymphatic invasion (ALI) in transitional cell carcinoma of the bladder (TCCB) from radical cystectomy specimens. METHODS: A retrospective review of 27 patients treated with radical cystectomy for TCCB was conducted. Comparisons were performed between three groups: PNI with or without ALI (PNI +/- ALI, 12 patients), ALI alone (8 patients), and a control group (no PNI or ALI) (7 patients). RESULTS: The mean patient age was 70 years (range 49 to 83). The overall median follow-up period was 11 months (range 1 to 32). PNI +/- ALI was predominantly found in Stage T3b disease (14 of 20 [70%] cases). The overall 1-year disease-free survival was 48%, 67%, and 83% for the PNI +/- ALI, ALI alone, and control groups, respectively. Nodal metastases (for all stages combined) were found in 6 of 12 (50%), 3 of 8 (38%), and 1 of 7 (14%) patients in the PNI +/- ALI, ALI alone, and control groups, respectively. Similarly, extranodal metastatic disease was found in 5 of 12 (42%), 4 of 8 (50%), and 1 of 7 (14%) patients in the PNI +/- ALI, ALI alone, and control groups, respectively. The percentage of deaths for the PNI +/- ALI, ALI only, and control groups were 33%, 50%, and 14%, respectively. CONCLUSIONS: In TCCB, perineural invasion with or without angiolymphatic invasion and angiolymphatic invasion alone are associated with a higher incidence of nodal and extranodal metastases and death.

Initial report on intravesical administration of N-trifluoroacetyladriamycin-14-valerate (AD 32) to patients with refractory superficial transitional cell carcinoma of the urinary bladder.

OBJECTIVES: This study was designed to assess the pharmacokinetics, safety, and antitumor activity of intravesically administered AD 32, a novel anthracycline, in patients with transitional cell carcinoma (TCC) of the bladder. METHODS: Six weekly doses of AD 32 (200 to 900 mg) were administered to 32 patients with superficial TCC who were candidates for intravesical treatment. Serum drug levels were measured during the 6-hour period after administration of the first, third, and sixth doses. Patients underwent bladder evaluations at 3-month intervals to determine responses to treatment. RESULTS: Very low levels of unmetabolized AD 32 and its two primary metabolites were measured in serum. The lack of systemic exposure was confirmed by the finding of only a few minor systemic adverse events. Local bladder irritation, the main toxicity associated with intravesical administration of AD 32, persisted for several days after each instillation. The maximum tolerated dose was 800 mg. Thirteen patients had complete responses to treatment, including 8 who remained disease free for 12.1 to 38.5 months. CONCLUSIONS: AD 32 is an active drug for the treatment of superficial bladder cancer. Further studies of intravesical administration of AD 32 are warranted.

A phase II trial of all-trans-retinoic acid in hormone-refractory prostate cancer: a clinical trial with detailed pharmacokinetic analysis.

Retinoids have been shown to have substantial anticancer activity in a number of preclinical and clinical situations. There are considerable epidemiologic, in vitro and in vivo data which indicate that retinoids may have a role in the prevention and therapy of human prostate cancer. Based on anecdotal evidence of response in one patient with hormone-refractory prostate cancer (HRPC), we conducted a phase II trial in HRPC during which we also examined changes in pharmacokinetics of all-trans-retinoic acid (ATRA) which occurred during therapy. Enrolled in the study were 17 patients with HRPC who received 50 mg/m2 ATRA three times daily orally on days 1-14, repeated every 22 days. The pharmacokinetics of ATRA were assessed with the first dose on day 1, again on day 14 and after a 7-day interruption in ATRA therapy on day 22. Patients were evaluable for response if they completed two 14-day courses of ATRA; among 13 such patients no responses were seen. Four patients were considered unevaluable for response owing to rapid disease progression in three and intercurrent illness in one. Apparent clearance of ATRA changed substantially during therapy: day 1 3779 +/- 4215 ml/min, day 14 7179 +/- 3197 ml/min, day 22 3213 +/- 2357 ml/min. Area under the curve was proportionately diminished on day 14 compared with day 1 and had returned to baseline by day 22. We conclude that ATRA is not active in HRPC. Failure of this agent in HRPC may be related to failure of drug delivery associated with enhanced mechanisms of ATRA clearance which occur within a few days of beginning ATRA treatment.

Management of stage T1b (A2) and stage T1c adenocarcinoma of the prostate.

The management of stage T1b (A2) and T1c adenocarcinoma of the prostate is somewhat controversial. With the widespread use of serum prostate-specific antigen (PSA) determinations, an increasing number of these cancers are likely to be diagnosed. Hence, it is important to formulate a cogent management strategy for these patients, because a large percentage of them can be expected to have clinically and pathologically localized disease. Expectant observation with deferred treatment, radical prostatectomy, radiation therapy (external beam or brachytherapy), and cryosurgical ablation are all primary therapeutic options that have individual merit. In this review, we attempt to analyze the results of the various treatment options for these patients and evolve a practical approach towards their management.

Simultaneous radical nephrectomy and repair of abdominal aortic aneurysm.

OBJECTIVES: The combination of abdominal aortic aneurysm repair with other intra-abdominal surgery is controversial. Most studies have shown that a variety of procedures can be performed at the same time as an aneurysm repair with little change in mortality or complication rates. We conducted a retrospective study to determine if aneurysm repair could be safely and effectively combined with radical nephrectomy. METHODS: We studied 10 patients who underwent combined abdominal aortic aneurysm repair and radical nephrectomy during a 4-year period. Results from this group were compared to a separate control group of 10 patients who underwent radical nephrectomy alone and another of 12 patients underwent abdominal aortic aneurysm repair alone, during the same time period. RESULTS: The overall mortality was 10% and significant complications occurred in an additional 10% of patients. Minor, self-limiting complications occurred in 30% of patients. There were no aortic graft infections that occurred in the entire series of patients at 18 months of mean follow-up. There were no remarkable differences in the entire series of patients and the combined values in a separate group of control patients who had undergone either procedure alone. CONCLUSIONS: Simultaneous radical nephrectomy for presumed renal cell carcinoma can be safely combined with repair of abdominal aortic aneurysm in selected patients.

Bladder cancer-associated nuclear matrix proteins.

The early diagnosis of bladder cancer is central to the effective treatment of the disease. Presently, there are no methods available to easily and specifically identify the presence of bladder cancer cells. The prevailing method for the detection of bladder cancer is the identification of bladder cancer cells by morphological examination of exfoliated cells or biopsy material by a pathologist. A hallmark of the malignant or transformed phenotype is an abnormal nuclear shape, the presence of multiple nucleoli, and altered patterns of chromatin organization. Nuclear structural alterations are so prevalent in cancer cells that they are commonly used as markers of transformation for many types of cancer. Nuclear shape is determined by the nuclear matrix, the dynamic skeleton of the nucleus. The nuclear matrix is the structural component of the nucleus that determines nuclear morphology, organizes the DNA in a three-dimensional fashion that is tissue specific, and has a central role in the regulation of a number of nuclear processes, including the regulation of DNA replication and gene expression. Previous investigations into prostate and breast cancer have revealed that nuclear matrix protein (NMP) composition undergoes alterations with transformation and that the nuclear matrix can serve as a marker for the malignant phenotype. In this study, we have identified NMPs with which it is possible to differentiate human bladder tumors from normal bladder epithelial cells. We examined the NMP composition of 17 matched tumor and normal samples from patients undergoing surgery for bladder cancer. We have identified six proteins present in all tumor samples that are not present in the corresponding normal samples and three proteins that are unique to the normal bladder tissues in comparison with the tumor samples. Five of the six bladder cancer-associated proteins were also identified in three human bladder cancer cells lines examined (253j, UMUC-2, and T24). Therefore, we have demonstrated that nuclear matrix composition is able to differentiate bladder cancer from normal bladder tissue and may provide useful tools for early detection and recurrence of the disease. Importantly, these markers may provide valuable tools for cytopathological screening for bladder carcinoma.

Evaluation of computerized tomography for staging of clinically localized adenocarcinoma of the prostate.

We conducted a retrospective review of 345 patients who underwent radical prostatectomy between 1991 and 1994 to assess the overall accuracy, sensitivity, and specificity of computerized tomography (CT) for detection of disease outside the prostate. In 139 patients who were eligible for study, the overall accuracy, sensitivity, and specificity were 51%, 79%, and 30%, respectively. For lymph node metastases only, the values were 89%, 7%, and 97%, respectively. For local extraprostatic extension, the values were 48%, 30%, and 83%, respectively. The overall positive predictive value of CT was 67% and the negative predictive value was 45%. CT has minimal to no utility in detecting extraprostatic disease in patients with clinically localized prostate cancer.

A cost containment strategy for radical retropubic prostatectomy: Results from implementation of a clinical pathway program.

Health care costs from the management of prostate cancer are estimated at $1.5 billion per year. As the number of radical prostatectomies being performed increases, a simultaneous rise in these costs can be expected. However, diminishing resources and the expanding managed care environment necessitate measures to curtail and even reduce these inflationary trends in health care expenditure. With this in mind, we established a collaborative clinical pathway for patients undergoing radical retropubic prostatectomy at our institution. The goals of the pathway were to reduce patient costs and hospital stay and to promote efficient use of resources for the procedure. We studied 71 patients who underwent radical retropubic prostatectomy and were managed according to the pathway during the first year of its implementation (July 1994 through July 1995). Outcome variables for these patients were compared with those of a group of 65 patients who underwent an identical procedure during the previous year (July 1993 through June 1994) before implementation of the pathway. Outcome parameters that were compared included hospital charges, length of stay (LOS), operating room (OR) time, units of packed red cells transfused, morbidity, and mortality. The overall hospital charges since implementation of the pathway decreased by 17.2% when corrected for inflation (p ≤ 0.006). LOS also decreased from a mean of 6.4 days to 5.2 days. There was no significant change in OR time. Overall complications remained unaffected (12.3% vs 12.6%). Based on these results, we conclude that establishment of an individualized, procedure-oriented clinical pathway for patients undergoing radical retropubic prostatectomy can result in significant reduction in patient costs without appreciable effect on morbidity and mortality.

Routine frozen section of pelvic lymph node specimens prior to radical retropubic prostatectomy is unnecessary in patients with prostate specific antigen.

Our prospective study was designed to evaluate the routine use of frozen section of pelvic lymph node specimens prior to radical prostatectomy in patients with pre-biopsy prostate specific antigen (PSA) levels less than 20 ng/ml. Included in our study were 241 patients who had clinically localized disease on digital rectal examination, a negative preoperative metastatic work-up, and a pre-biopsy serum PSA of less than 20 ng/ml. If a palpable abnormality of pelvic lymph nodes was detected at the time of surgery, specimens were sent for frozen section analysis. Lymphatic specimens that were palpably normal were sent for permanent section only. Ten (4.1%) of the 241 patients had pelvic lymph node metastases demonstrated by permanent section. Of the patients with lymph node metastasis, 50% had Gleason scores of 8-10 on their needle biopsy specimens. None of these patients had frozen section analysis of their lymph nodes. Frozen section failed to detect lymph node metastasis in all cases analyzed. Routine frozen section analysis of pelvic lymphadenectomy specimens in patients with clinically localized prostate cancer, Gleason score 2-7 on the needle biopsy, and prebiopsy PSA of less than 20 ng/ml is unnecessary.