A phase II trial of CI-958 in patients with hormone-refractory prostate cancer.

PURPOSE: To assess the antitumor activity of the benzothiopyranoindazole CI-958 ¿5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H- [l]benzothiopyrano[4,3,2-cd]-indazol-8-ol trihydrochloride¿ in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m(2) every 3 weeks. PATIENTS AND METHODS: Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria. RESULTS: All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a >50% decline maintained for >30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1-23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions. CONCLUSIONS: CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.

Actinomycin D revisited in testicular cancer. A case report.

BACKGROUND: Between 20-30% of patients with advanced germ cell tumors relapse or fail to achieve a complete response to conventional cisplatin based chemotherapy. Ifosphamide has been used very effectively in combination with cisplatin and etoposide (VIP) or in combination with cisplatin and vinblastine (VeIP). Actinomycin D with chlorambucil and methotrexate was widely used in the 1960s with complete responses in 20% of patients and long term survival of 6-10%. There exists no information on the use of actinomycin as a salvage in cisplatin refractory patients. METHODS AND RESULTS: One patient with metastatic germ cell tumor who failed chemotherapy with cisplatin and ifosphamide was successfully treated with an actinomycin D based regimen. CONCLUSIONS: Actinomycin D is an active agent in testicular cancer and maybe used in patients refractory to platinum.

Laparoscopic vesicopsoas hitch for infiltrative ureteral endometriosis.

OBJECTIVE: To report the technique and outcome of a laparoscopic vesicopsoas hitch used for the treatment of infiltrative ureteral endometriosis. DESIGN: Case report. SETTING: A tertiary care center. PATIENT(S): A 36-year-old woman with infiltrative endometriosis of the ureter. INTERVENTION(S): A laparoscopic vesicopsoas hitch. MAIN OUTCOME MEASURE(S): The return of normal ureteral function as measured by IV pyelography and ultrasonography. RESULT(S): After partial ureteral resection, it was noted that a tension-free anastomosis to the bladder was not possible. Thus, a laparoscopic vesicopsoas hitch was performed. CONCLUSION(S): A vesicopsoas hitch can be performed successfully by laparoscopy.

Methotrexate tolerance in patients with ileal conduits and continent diversions.

BACKGROUND: Methotrexate is readily absorbed from the intestinal tract. When given to patients with urinary diversion to the intestinal tract, methotrexate may be reabsorbed into the circulation, thus increasing its serum concentration and potentially increasing its toxicity. METHODS: Forty-eight patients with transitional cell carcinoma of the urinary tract who had undergone cystectomy and either an ileal conduit or a continent diversion were evaluated for their tolerance of chemotherapy. Of the 42 evaluable patients, 23 had a continent diversion and 19 had an ileal conduit. None of the patients with the continent diversion had an indwelling Foley catheter during the course of chemotherapy. RESULTS: There were no statistically significant differences in incidence of fever or neutropenia, mucositis, dose modification, or delay in chemotherapy between the two groups. When compared with a group of patients with native bladders who received the same chemotherapy, patients with continent diversions did not have increased incidence or severe toxicity from chemotherapy. CONCLUSIONS: Patients with continent diversions tolerated chemotherapy as well as patients with ileal conduits.

Transrectal ultrasound appearance of hematolymphoid malignancies involving the prostate.

OBJECTIVES: Although the clinical presentation and physical examination findings in patients with lymphoma or leukemia involving the prostate have been described previously, the transrectal ultrasound appearance of hematolymphoid malignancies involving the prostate has not been previously described. METHODS: Nine patients with prostate cancer diagnosed by transrectal ultrasound-guided prostate biopsies were found to have hematolymphoid malignancies involving the prostate at the time of subsequent radical prostatectomy and pelvic lymph node dissection. The ultrasound images and prostate needle biopsy results are presented. RESULTS: Prospective analysis of transrectal ultrasound images revealed no abnormality other than hypoechogenicity typical of prostate cancer in 7 of the 9 patients (77.8%). In 2 patients, the ultrasound images were free of any abnormalities. In 2 of the 9 patients (22.2%), the prostate needle biopsies demonstrated suspicious lymphocytic infiltrate in addition to prostate cancer. CONCLUSIONS: Transrectal ultrasound does not detect hematolymphoid malignancies involving the prostate. Ultrasound-guided biopsies of the prostate have a very low rate of detecting these malignancies.

Hematolymphoid malignancies diagnosed at the time of radical prostatectomy.

PURPOSE: The clinical impact of hematolymphoid malignancies discovered during radical prostatectomy has not been previously defined to our knowledge. MATERIALS AND METHODS: From October 1988 to September 1995, 1,092 patients underwent radical retropubic prostatectomy. RESULTS: Of 1,092 radical prostatectomy specimens, 13 (1.2%) were found to have hematologic malignancies involving the prostate and/or lymph nodes sampled during concomitant pelvic lymph node dissection. The malignancies detected included Hodgkin's disease (3) and hairy cell leukemia (1), which required further therapy. However, 9 of the 13 patients (62%) demonstrated either chronic lymphocytic leukemia (3) or low grade, small lymphocytic lymphoma (6), which requires symptomatic treatment only. The transrectal ultrasound guided prostate biopsies revealed suspicious lymphocytic infiltrate in addition to prostatic adenocarcinoma in 2 of the 13 patients (15%). CONCLUSIONS: The majority of hematologic malignancies discovered at radical prostatectomy do not require further treatment and should not delay treatment of prostatic adenocarcinoma.

Transrectal ultrasound appearance of prostatic granulomas secondary to bacillus Calmette-Guerin instillation.

PURPOSE: To our knowledge the transrectal ultrasound appearance of prostatic granulomas occurring after intravesical bacillus Calmette-Guerin (BCG) therapy has not been thoroughly described. MATERIALS AND METHODS: A total of 13 men with a history of transitional cell carcinoma of the bladder treated with intravesical BCG underwent transrectal ultrasound followed by prostate biopsy and/or cystoprostatectomy. RESULTS: Of the 13 patients studied 9 (69.2%) had intensely hypoechoic lesions anteriorly in the transition zone of the prostate on ultrasound images. The lesions were histologically proved to be necrotizing granulomas. CONCLUSIONS: Prostatic granulomas secondary to BCG instillation appear as distinct, intensely hypoechoic anterior lesions within the transition zone of the prostate. Prostatic adenocarcinoma arising in the transition zone is usually not visible and would not be easily confused with granulomas. However, since transitional cell carcinoma involving the prostate can appear hypoechoic in the transition zone, transrectal or transurethral tissue sampling may be indicated.

Primary thyroidlike carcinoma of the kidney.

We present a unique papillary thyroidlike carcinoma of the kidney. The patient had an incidentally discovered renal mass that, histologically and immunohistochemically, resembled papillary thyroid carcinoma. Workup revealed no primary site other than the kidney and no evidence of metastasis. This is the first reported case of a malignant papillary thyroidlike cancer of the kidney.

A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer.

PURPOSE: Standard treatment for muscle invasive transitional cell cancer of the bladder is radical cystectomy. Despite careful staging, the majority of cancers with regional lymph node involvement and/or invasion to adjacent organs eventually recur. We investigated the benefit of chemotherapy with cisplatin, methotrexate and vinblastine (CMV) after radical cystectomy. MATERIALS AND METHODS: A prospective trial was done in which patients were randomized after cystectomy to receive either 4 cycles of CMV chemotherapy or observation. At relapse, patients were treated with standard CMV chemotherapy for metastatic disease at our institution. RESULTS: Of 55 patients who entered this trial 1 was ineligible and in 4 it is too soon to be evaluated. Of the 50 evaluable patients 25 were randomized to receive adjuvant CMV chemotherapy and 25 were observed. In the CMV arm 12 (48%) and in the observation arm 5 (25%) never had recurrence. With a median followup of 62 months and no patient with less than 2 years of followup, the freedom from progression in the adjuvant chemotherapy group was superior to that in the observation group (median 37 versus 12 months, respectively, p = 0.01). Median survival in the adjuvant group was 63 months compared to 36 months for the observation group. Surprisingly, some cases with relapse could be salvaged with CMV chemotherapy, perhaps contributing to this lack of difference in overall survival (p = 0.32). CONCLUSIONS: Treatment with CMV chemotherapy after radical cystectomy is an acceptable approach in patients with stages p3b and p4N0 or N1 transitional cell carcinoma of the bladder. Further studies must be performed to determine whether these results can be extrapolated to patients with more limited disease (stages p2 and p3a) who are currently treated with radical cystectomy or definitive irradiation.

Nerve sparing radical prostatectomy: a different view.

Erectile dysfunction was evaluated in 459 men with prostate cancer before and after radical prostatectomy. Potency was defined as the ability to achieve unassisted intercourse with vaginal penetration. Of the patients 51 were potent postoperatively, including 2 of 187 (1.1%) undergoing surgery without nerve sparing, and 27 of 203 (13.3%) undergoing unilateral and 22 of 69 (31.9%) undergoing bilateral nerve sparing prostatectomy. Less than half of the patients who were sexually active postoperatively were satisfied with the erections or achieved intercourse at least once a month. Postoperative potency was statistically related to the number of neurovascular bundles spared, frequency of intercourse preoperatively, absence of seminal vesicle or lymph node involvement with cancer, absence of postoperative incontinence or strictures, patient age and cancer volume.

Incontinence and vesical neck strictures following radical retropubic prostatectomy.

OBJECTIVES: To evaluate the incidence and severity of vesical neck strictures and urinary incontinence after radical retropubic prostatectomy (RRP) for prostate cancer. METHODS: Between August 1983 and December 1991, 481 consecutive patients underwent RRP by 1 of 2 senior surgeons. Strictures were treated by passing a urethral sound. Incontinence was measured by asking patients for a daily "pad count" of pads required to control urinary leakage. Results were compared to patient age, tumor volume, number of neurovascular bundles spared, preoperative urinary complaints, and previous transurethral resection of the prostate. RESULTS: Of 456 patients with adequate follow-up to determine stricture formation, 82.5% had no strictures, 6.8% required a single dilation, 3.7% required 2 dilations, 3.1% required 3 dilations, and 3.9% required more than 3 dilations. Risk of stricture formation was unrelated to every variable studied. Of 458 patients with adequate follow-up to determine recovery of continence, 80.1% required no pads, 8.1% required 1 to 2 pads a day, 6.6% required 3 to 5 pads a day, and 5.2% were totally incontinent 1 year or more after surgery. Incontinence was closely associated with postoperative urinary urgency. CONCLUSIONS: Strictures are a common but easily managed complication of RRP for prostate cancer. Despite substantial surgical experience, we report a somewhat higher rate of postoperative incontinence than other recently reported series. Our experience is more closely matched by published surveys of patient-reported complications after RRP.

Utility of preoperative serum prostate-specific antigen concentration and biopsy Gleason score in predicting risk of pelvic lymph node metastases in prostate cancer.

OBJECTIVES: To determine the accuracy of the preoperative serum concentration of prostate-specific antigen (PSA) plus the Gleason pathology score of biopsy specimens in predicting the presence of disease in the pelvic lymph nodes in patients with prostate cancer. METHODS: The medical records of all patients treated for prostate cancer at eight medical centers from January 1988 to June 1993 were reviewed. There were 932 patients with newly diagnosed prostate cancer for whom all relevant data were available who had undergone pelvic lymphadenectomy with (n = 912) or without (n = 20) radical prostatectomy. The rate of false-negative predictions of metastases based on combined preoperative biopsy Gleason score and serum PSA concentration was analyzed. A multivariate logistic regression analysis was performed to assess the value of preoperative serum PSA and biopsy Gleason scores individually and in combination in predicting pelvic lymph node metastases. RESULTS: The false-negative rate of metastases was 0% for preoperative PSA concentrations < or = 6 ng/mL and biopsy Gleason scores < or = 5 (n = 142) and 1.0% for PSA concentrations < or = 10 ng/mL and Gleason scores < or = 6 (n = 388). The 95% upper confidence limit for the rate of false negativity at this PSA cut-off level was 2.0%. A combination of preoperative serum PSA levels and biopsy Gleason scores provided the best prediction for the false-negative rates. CONCLUSIONS: For patients with newly diagnosed prostate cancer who have biopsy Gleason scores < or = 6 and preoperative PSA concentrations < or = 10 ng/mL (42% of our series), a staging pelvic lymphadenectomy appears to be unnecessary. The substantial cost associated with both cross-sectional imaging and staging lymphadenectomy may therefore be avoidable in this group of patients.

Transrectal ultrasound in the evaluation of rhabdomyosarcoma involving the prostate.

OBJECTIVE: To evaluate transrectal ultrasound as a means of diagnosis and of monitoring patients with rhabdomyosarcoma involving the prostate. PATIENTS AND METHODS: Serial transrectal ultrasonography was utilized to evaluate prostatic rhabdomyosarcoma in three patients. RESULTS: Unlike prostatic adenocarcinoma and transitional cell carcinoma involving the prostate, which are predominantly hypoechoic, the echogenicity of rhabdomyosarcoma is similar to that of the normal prostate. Transrectal ultrasound provided a simple means of monitoring prostate size and sampling tissue in these patients. CONCLUSION: Transrectal ultrasound imaging can be useful in both diagnosis and evaluation of treatment response as well as provide easy access for biopsies in patients with rhabdomyosarcoma involving the prostate.

Spermatic cord metastasis from transitional cell carcinoma of the bladder.

A case of transitional cell carcinoma of the bladder metastasizing to the spermatic cord is reported. This represents the only clinically recognized site of tumor recurrence in a man treated with radical cystoprostatectomy followed by four cycles of adjuvant cis-platinum/methotrexate/vinblastine (CMV) chemotherapy for Stage D1 disease (local pelvic lymph node involvement). The existing literature concerning metastatic tumors of the spermatic cord is reviewed.

[Effect of the natural history on management of adenocarcinoma of the prostate]. / Einfluss der natürlichen Geschichte auf die Handhabung des Adenokarzinoms der Prostata.

The natural history of prostate cancer has long been regarded as unpredictable. The discrepancy between histologically identifiable (40%) and clinically diagnosed carcinomas (8%) led to the term of "latent" prostate cancer and to considerable diagnostic and therapeutic dilemmas. Based on our previous studies showing that biological aggressivity of prostate cancer is a direct function of tumor volume and that tumor volume and serum PSA are proportional, we evaluated two basically different groups of patients. The first group consisted of 43 patients with untreated carcinomas of the prostate followed with serial PSA determinations. The exponential (log-linear) rise in PSA led us to the conclusion of an exponential tumor growth rate. The median doubling time of clinically organ-confined tumors was 4 years and became shorter with higher clinical stages and poorly differentiated histological grades. The second group consisted of 139 patients who underwent cystoprostatectomy for bladder cancer and had no evidence for simultaneously identifiable prostate cancer. In 55 patients (40%), unsuspected prostate cancer was found in the specimen; the volume distribution of these carcinomas was exponential. These 139 men included 11 (7.9%) who had a prostate cancer with a volume greater than 0.5 cm3, corresponding to the 8% risk for a man being diagnosed within his lifetime with a clinically significant carcinoma of the prostate. We conclude that the other 44 carcinomas, which were less than 0.5 cm3 in volume, will never reach clinical significance because of their small size and their long doubling time; in this sense they can be considered latent.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal, renal pelvis and ureteral tumors: should retroperitoneal nodes be treated?

Transitional cell carcinoma of the upper urinary tract is rare. Tumors arising in the renal pelvis and calyces should be treated with nephroureterectomy, irrespective of stage and grade. Low-grade, low-stage ureteral tumors may be treated with conservative resection in order to preserve renal function. High-grade, more advanced ureteral tumors should be treated with nephroureterectomy because of the high incidence of recurrence associated with local resection. The role of lymphadenectomy for upper tract transitional cell carcinoma has never been evaluated; however, it is recommended for better staging of the disease and for recommendations regarding adjuvant therapy. Adjuvant radiation therapy to sterilize microscopic residual disease and prevent local recurrence is logical. The role of adjuvant chemotherapy is under investigation.

[Epidemiologic observations on prostate cancer based on tumor volumes]. / Epidemiologische Betrachtungen zum Prostatakarzinom basierend auf dem Tumorvolumen.

Using the SEER Program of the NCI, and the U.S. total mortality rates, we calculated the probability at birth of being diagnosed with prostate cancer within one's lifetime to be 8.8%, and we subtracted the microscopic stage A cancers too small to ever be of clinical significance which gave a final probability of 8%. Prostates were examined in 139 consecutive, unselected cystoprostatectomies from patients with bladder cancers who were unknown to have prostate cancer. Prostate cancer was found in 55 patients (40%); the volume of the largest cancer in each of these 55 prostates was determined by histologic morphometry. We identified the 8% of these 139 cystoprostatectomies with the largest volume of prostate cancer. The largest 11 of the 55 cancers represented 7.9% of the 139 cystoprostatectomies. These cancers ranged in volume from 0.5 cc to 6.1 cc, representing only 20% of all patients with prostate cancer. Thus, if one accepts the strong evidence that cancer progression is proportional to cancer volume, we conclude that prostate cancers larger than 0.5 cc appear to correspond to the 8% of men who will be diagnosed with a clinically significant carcinoma, as derived from SEER data. Conversely, those 80% of prostate cancers under 0.5 cc are probably not destined to reach clinically significant size in view of the very long doubling time of this cancer.

Incidentally discovered solid renal masses: what are they?

In 36 of 99 consecutive patients operated on for the presumptive diagnosis of renal carcinoma the tumour was discovered accidentally during investigations for a variety of complaints. CT and ultrasound scans were responsible for discovery of the tumour in 24 of the 36 patients. Renal carcinoma accounted for 92% of incidentally discovered solid renal masses. Of 33 incidentally diagnosed renal carcinomas 27 were stage 1. An incidentally discovered solid renal mass should be regarded as a low stage renal carcinoma until proven otherwise.

Cisplatin, methotrexate and vinblastine plus surgical restaging for patients with advanced transitional cell carcinoma of the urothelium.

Chemotherapy with cisplatin, methotrexate and vinblastine (CMV) is active in advanced transitional cell carcinoma of the urothelium. Aggressive surgical resection of residual disease following responses produced by CMV was incorporated into a combined modality approach. Between 1982 and 1990, 64 patients were entered into the study. Of 55 patients evaluable for response 11 (20%) had a pathological complete response, 14 (25%) achieved a complete response following resection of residual disease and 5 (9%) whose disease was not surgically restaged had a clinical complete response. The overall complete response rate was 55%. Patients with liver, lung or bone involvement had significantly decreased survival compared to patients without visceral disease (p = 0.002). With a median followup exceeding 50 months, 14 patients (22% of all patients entered into the study) were free of disease at 23 to 98+ months. There were no deaths related to treatment. CMV produced high rates of response in patients with advanced disease, including those with distant metastases. Surgical resection of residual disease following responses produced by chemotherapy proved to be feasible, without treatment related mortality, and may have prolonged survival in selected cases.