Effect of a nutritional supplement containing vitamin E, selenium, vitamin c and coenzyme Q10 on serum PSA in patients with hormonally untreated carcinoma of the prostate: a randomised placebo-controlled study.

OBJECTIVE: To assess the effect of a nutritional supplement containing vitamin E, selenium, vitamin C and coenzyme Q10 on changes in serum levels of PSA in patients with hormonally untreated carcinoma of the prostate and rising serum PSA levels. METHODS: Eighty patients were randomised to receive a daily supplement with either vitamin E, selenium, vitamin C, coenzyme Q10 (intervention group) or placebo over 21 weeks. Serum levels of PSA were assessed at baseline (-2, -1, 0 weeks) and after 6, 13, 19, 20 and 21 weeks. Mean changes in log serum level of PSA, testosterone, dihydrotestosterone, luteinizing hormone and sex hormone binding globulin over 21 weeks between the verum and the placebo group were compared by analysis of covariance. RESULTS: Seventy patients completed the study (36 verum; 34 placebo). Compliance was >90% in all patients. In the intervention group, plasma levels of vitamin E, selenium and coenzyme Q10 increased significantly over the 21 weeks study period. No significant differences in serum levels of PSA, testosterone, dihydrotestosterone, luteinizing hormone or sex hormone binding globulin (p>0.2) were observed between the intervention and control group. CONCLUSION: Our results indicate that supplementation of a combination of vitamin E, selenium, vitamin C and coenzyme-Q10 does not affect serum level of PSA or hormone levels in patients with hormonally untreated carcinoma of the prostate.

Strontium(89) chloride versus palliative local field radiotherapy in patients with hormonal escaped prostate cancer: a phase III study of the European Organisation for Research and Treatment of Cancer, Genitourinary Group.

OBJECTIVES: To compare toxicity, subjective response rate, time to subjective progression and overall survival in patients with painful bone metastases of hormone-resistant prostate cancer (HRPC) treated with a single intravenous injection of 150MBq (4mCi) Strontium(89) Chloride (S) or palliative local field radiotherapy (R) with the usual radiotherapy regimen used at each centre. The costs of both treatments were also assessed. PATIENTS AND METHODS: 101 patients were randomized to S and 102 to R. Time to event endpoints were compared with the Logrank test and Kaplan-Meier curves, in the intent-to-treat population (2-sided alpha=0.05). RESULTS: Baseline characteristics of both groups were comparable. There was a borderline statistically significant difference in overall survival in favour of the local field radiotherapy (R: 11 months; S: 7.2 months; p=0.0457). There was no difference in progression-free survival or time to progression. Subjective response was seen in 34.7% in the S-arm and in 33.3% in the R-arm. A biochemical response was observed in 10% and 13% of the R- and S-groups, respectively. There was no difference in treatment toxicity between the two groups. CONCLUSION: In symptomatic HRPC, pain treatment with local field radiotherapy is associated with a better overall survival compared to Strontium(89). The lower costs of local field radiotherapy also favour the use of this treatment in patients with HRPC. The reason for the apparent survival benefit of localised radiation treatment is not clear.

Proton MR spectroscopy of prostatic tissue focused on the detection of spermine, a possible biomarker of malignant behavior in prostate cancer.

To investigate whether polyamines may be valuable diagnostic and prognostic markers in prostate cancer, the presence of polyamines was studied in various human prostatic tissues using both proton magnetic resonance (MR) spectroscopy and high-pressure liquid chromatography (HPLC). The HPLC results showed that normal and benign hyperplastic prostatic tissues were characterized by a high content of spermine. Spermine levels were reduced in tumor tissue, especially in prostatic carcinoma with metastases, and in xenografts of human prostatic carcinoma cells. These preliminary results indicate that spermine may be used as a biomarker for malignant behavior. The MR spectroscopy study showed that it is possible to detect spermine resonances in prostatic biopsy material by one-dimensional and two-dimensional J-resolved MR spectroscopy at high field (600 MHz). Localized one-dimensional in vitro MR spectra obtained at the clinical field strength of 1.5 T showed spermine signals in the region between 3.0 and 3.3 ppm. In in vivo MR spectra of the human prostate, however, these signals were obscured by resonances of choline (3.2 ppm) and creatine (3.0 ppm).

High-intensity focused ultrasound (HIFU) followed after one to two weeks by radical retropubic prostatectomy: results of a prospective study.

BACKGROUND: High-intensity focused ultrasound (HIFU) consists of focused ultrasound waves emitted from a transducer that are capable of inducing tissue damage. Experimental studies have shown clear damage of malignant tissue exposed to HIFU, but knowledge of in vivo effects is limited. We studied the safety and efficacy of HIFU in patients with a T1-2 N0) M0 prostate carcinoma. METHODS: HIFU treatment was performed under general anesthesia with the Ablatherm device (Technomed Medical Systems, Lyon, France), 7-12 days prior to radical prostatectomy. Only the lobe in which carcinoma was confirmed was treated. The radical prostatectomy specimen was examined histopathologically, and the changes were compared with treatment goals. RESULTS: So far, 9 patients have been treated. On histology, a sharp delineation was noted between areas treated with HIFU and untreated areas. On the dorsal border, however, incomplete destruction of tissue was noted, and in 2 cases a small residual tumor was seen in this region. In all cases complete necrosis was seen in the treated region. CONCLUSIONS: Histology reports of radical prostatectomy specimens of patients operated 7-12 days after HIFU treatment showed marked and complete necrosis in the treated area. Due to incomplete tissue destruction at the dorsal side, however, a small focus of residual vital tumor was found in 2 of 9 patients.

Intratumoral distribution of two consecutive injections of chimeric antibody G250 in primary renal cell carcinoma: implications for fractionated dose radioimmunotherapy.

Tumor uptake of the chimeric G250 (cG250) monoclonal antibody (mAb) in patients with primary renal cell carcinoma (RCC) is among the highest reported in solid tumors. However, as observed in other tumor types, the intratumoral distribution of the antibody is highly heterogeneous, which may limit the efficacy of radioimmunotherapy. A number of highly dynamic physiological factors have been postulated that may contribute to heterogeneous tumor uptake of antibodies. Their impact on tumor uptake of antibodies may vary from one tumor region to another as well as from one day to the next. Here, we report on a clinical study that was designed to investigate whether the pattern of mAb cG250 uptake within RCC tumors is altered with subsequent injections. Ten patients with a clinical diagnosis of primary RCC were studied. Nine days before surgery, patients received 125I-cG250 (5 mg of cG250, 50 microCi of 125I), followed by a second injection of 131I-cG250 (5 mg of cG250, 3.5 mCi of 131I) 4 days later. Postsurgery, the tumor was cut into (1-cm) thick slices. Slices were imaged on a gamma camera, and the slice with the most pronounced heterogeneity in 131I-cG250 distribution was selected and cut into 1-cm3 cubes. Each cube was analyzed for 121I-cG250 and 131I-cG250 uptake, and the 131I/125I ratio was determined. For each tumor slice, the distribution patterns of both isotopes were reconstructed and compared with each other. All tumors analyzed showed a heterogeneous distribution of both isotopes throughout the tumor slice; focal uptake in some areas of a tumor reached very high levels (up to 0.19% injected dose/g), whereas other tumorous areas of the same slice showed much lower uptake (as low as 0.0047% injected dose/g). Remarkably, in all tumors, the distribution pattern of both injections was identical: without exception, in all samples analyzed (n = 692), the uptake of 125I-cG250 was similar to 131I-cG250 uptake. Overall, the 131I/125I ratio was 1.64+/-0.31 (mean+/-SD). The constant 131I/125I ratios, observed in all tumor samples investigated, indicate that the tumor parameters governing cG250 mAb uptake were not altered significantly within the time period studied. In addition, the results of this study suggest that multiple radiolabeled antibody injections, administered within short time periods, will target the same areas within a tumor and, thus, will not solve the problem of heterogeneous tumor uptake of antibody.

Evaluation of chemotherapy in advanced urinary bladder cancer with fast dynamic contrast-enhanced MR imaging.

PURPOSE: To evaluate if the failure of chemotherapy in patients with advanced urinary bladder cancer can be predicted early in the course of chemotherapy with fast dynamic contrast material-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: In this prospective study, 22 consecutive patients with histologically proved advanced urinary bladder cancer underwent MR imaging before and after two, four, and six cycles of chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin (MVAC). The response after two chemotherapy cycles was evaluated by using conventional tumor size parameters at unenhanced MR imaging and with changes in the time to the start of tumor or lymph node enhancement at fast dynamic contrast-enhanced MR imaging. The results obtained with these techniques were compared with the findings at histopathology in cystectomy (n = 9) or multiple transurethral resection (n = 13) specimens obtained after completion of chemotherapy. RESULTS: After two MVAC cycles, the accuracy, sensitivity, and specificity in distinguishing responders from nonresponders with conventional MR imaging were 73%, 79%, and 63%, respectively. With the dynamic technique, these were 95%, 93%, and 100%, respectively. Although the differences between these values are not significant (P = .48 for sensitivity, .25 for specificity, and .07 for accuracy), the data indicate that dynamic enhanced MR imaging performed better than unenhanced MR imaging. Dynamic imaging yielded correct results after two MVAC cycles in 21 cases, and in all cases after four cycles. After four MVAC cycles, the accuracy of dynamic MR imaging was significantly better (P < .05). Persisting early enhancement after four MVAC cycles correctly corresponded with lack of response in all nine cases, and after two cycles in eight of these cases. The unenhanced MR technique showed initial tumor size reduction in three of these cases. CONCLUSION: Conventional and dynamic enhanced MR imaging were used to evaluate chemotherapy after two, four, and six cycles of MVAC in 22 patients with bladder cancer. After two cycles, dynamic MR imaging helped detect 13 of 14 responders and eight of eight nonresponders. It helped detect five of seven lymph node responders and two of two nonresponders. Thus, it may be possible to predict after two MVAC cycles whether a patient will respond to chemotherapy.

[Benign prostatic hyperplasia; recommendations for transmural care. Working Group, Dutch College of General Practitioners and Netherlands College of Urologists]. / Benigne prostaathyperplasie; aanbevelingen voor transmurale zorg.

Both the Netherlands College of Urologists (NVU) and the Dutch General Practice College (NHG) in recent years published guidelines for the management of benign hypertrophy of the prostate (BPH). The two differ in a number of respects and are not always consistent. The differences between the GP's and urologists' guidelines are mostly to be attributed to the difference in the patient populations visiting the GP and the urologist, respectively. In order to arrive a better adjustment concerning BPH patients between general practice and specialists, a team composed of NVU and NHG has drawn up 'Recommendations for transmural care'. These recommendations concern four subjects: diagnosis of micturition abnormalities, indication for examination of cancer of the prostate, drug treatment, indications for referring and re-referring of patients with micturition problems.

Dynamic TurboFLASH subtraction technique for contrast-enhanced MR imaging of the prostate: correlation with histopathologic results.

PURPOSE: To assess whether a TurboFLASH (fast low-angle shot) magnetic resonance (MR) sequence can improve the accuracy of fast spin-echo (SE) endorectal coil MR imaging in the staging and localization of prostate cancer. MATERIALS AND METHODS: In 57 patients with prostate cancer, MR imaging was performed with the following sequences: T1-weighted SE, T2-weighted fast SE, single-section gadolinium-enhanced dynamic subtracted TurboFLASH (one image every 1.25 or 2.5 seconds), and late-phase gadolinium-enhanced T1-weighted SE. Retrospectively, two blinded independent readers graded onset and steepest slope of enhancement and assessed tumor involvement and capsular penetration. MR findings were correlated with histopathologic results. RESULTS: On TurboFLASH images, prostate cancer was characterized by early and rapidly accelerating enhancement compared with that of surrounding tissues. Average sensitivity, specificity, and accuracy for detection of tumor involvement for the two readers with TurboFLASH images were 73.5%, 81.0%, and 77.5%. These values with fast SE images were 57.5%, 80.5%, and 72.0%. Depiction of capsular penetration and delineation and staging of tumor were better when TurboFLASH images were included with fast SE images. Differences between the two sequences, however, were not statistically significant. CONCLUSION: Because the TurboFLASH sequence did not statistically significantly improve tumor localization and staging results, routine use is not recommended. The technique may be useful for selected patients with equivocal evidence of capsular penetration.

In vivo proton MR spectroscopy reveals altered metabolite content in malignant prostate tissue.

BACKGROUND: Recently the potential of magnetic resonance (MR) methods for non-invasive diagnosis and therapy evaluation of prostate cancer has improved substantially. In this study proton MR spectroscopy (1H MRS) was explored for the detection of cancer in the prostate. PATIENTS AND METHODS: Employing an endorectal probe localized 1H MRS and contrast enhanced MR imaging was performed on the prostate of healthy volunteers and of patients with benign prostatic hyperplasia (BPH) and/or prostate cancer (PCa). RESULTS: 1H MR spectra of the human prostate showed major signals for citrate, creatine and choline compounds. For cancer tissue the average citrate/choline signal ratio was significantly lower than for BPH and non-cancerous peripheral and central zone tissue, but individual ratios overlapped with ratios for normal central zone and BPH tissue. Low citrate/choline ratios in tumour tissue correspond with early MR contrast enhancement. CONCLUSIONS: 1H MRS has potential for non-invasive detection and follow-up of tumours in the prostate.

Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250.

PURPOSE: Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody. PATIENTS AND METHODS: Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi 131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained of surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed. RESULTS: In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage of the injected dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250 uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients. CONCLUSION: 131I-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid tumors. Since tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250 are administered (> 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC.

Treatment in germ cell tumours: state of the art.

Although the majority of patients with disseminated germ cell tumours can be cured with cisplatin-based chemotherapy, mortality is still up to 20%. Several prognostic factors have been identified to differentiate between patients with a good, intermediate or poor prognosis. In this review we discuss the recent chemotherapy trials, which were designed to reduce toxicity in good-prognosis patients and to improve efficacy in intermediate- and poor-prognosis patients. In good-prognosis patients it is obvious that the omission of bleomycin and the replacement of cisplatin by carboplatin has no place in first-line standard treatment. The reduction of four standard courses of bleomycin, etoposide and cisplatin (BEP) to three is shown possible in one study, but a confirmatory study is currently ongoing in the EORTC. In intermediate- and poor-prognosis patients, the use of new agents or alternating regimens (with or without shortened intervals) did, by now, not improve final outcome. The role of high-dose chemotherapy remains to be determined. Against this background, four courses of standard-dose BEP should still be considered treatment of first choice in the majority of patients with disseminated germ cell tumours. Furthermore, the policy in clinical stage I disease has been reviewed. In clinical stage I seminoma patients the policy is to apply adjuvant radiotherapy, while the strategy in patients with non-seminomatous tumours (surveillance, retroperitoneal lymph node dissection or adjuvant chemotherapy in high-risk patients) depends highly on the local situation, such as the operating skills of the urologist, and on the possibilities for tight follow-up. Of patients with true resistance for up-front BEP chemotherapy 90% will normally die. In patients who achieve a complete response on first-line chemotherapy, but relapse thereafter 30% will have no evidence of disease with second-line chemotherapy (VIP). In this group of patients results with high-dose chemotherapy seem promising, but its value should preferentially be determined in either a randomized fashion or by long-term follow-up from a large group of patients according to a similar protocol. The use of post-chemotherapy surgery is an essential part of management for metastatic non-seminomatous germ cell tumours, while the majority of residual masses in pure seminoma will disappear spontaneously, and frequent follow-up is recommended instead of surgical intervention.

Intratumoral nuclear morphologic heterogeneity in prostate cancer.

OBJECTIVES: Tumor heterogeneity can be measured by quantifying variance of nuclear characteristics by image analysis. Heterogeneity of cell nuclear features correlated with increased local progression in prostate cancer. In the present study, the influence of tumor heterogeneity on prostate-specific antigen (PSA) recurrence after radical retropubic prostatectomy was analyzed and tumor heterogeneity was compared in patients with and without neoadjuvant hormonal therapy. METHODS: Retrospectively, radical prostatectomy material of 44 patients without and 12 patients with neoadjuvant hormonal treatment with a postoperative follow-up of at least 4 years was studied. Each prostatectomy specimen was systematically embedded in paraffin, and each tumor area within the prostate was marked and analyzed by an image analysis system for 32 nuclear features comprising nuclear shape, size, DNA content, and chromatin pattern. Several clinical features were available: preoperative serum PSA, hemoglobin concentration, Karnofsky score, tumor stage, and Gleason score. RESULTS: Increased tumor heterogeneity, as expressed by differences in karyometric values between tumor areas in nuclear shape and chromatin pattern within the tumor, was significantly correlated with earlier PSA recurrence rate. As compared with nonpretreated patients, hormonally pretreated specimens showed smaller and less heterogeneous tumors. In particular, chromatin pattern heterogeneity was decreased in patients who underwent preoperative hormonal treatment compared with patients who were not pretreated. However, decreased heterogeneity was accompanied by a higher percentage of aneuploid areas per tumor in the pretreated patients. Cox regression analysis showed that karyometric determination of nuclear shape heterogeneity in combination with preoperative PSA level could predict time to PSA recurrence after radical prostatectomy in patients without hormonal pretreatment. CONCLUSIONS: Increase in karyometric tumor heterogeneity in nuclear shape and chromatin pattern was correlated with a shorter PSA recurrence-free interval after radical prostatectomy. Preoperative PSA and karyometric tumor heterogeneity were the best predictors of PSA recurrence in a multivariate analysis. Intratumoral heterogeneity was decreased in patients with prostate cancer who underwent neoadjuvant hormonal therapy.

Toxicity and results of MVAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapy in advanced urothelial carcinoma.

OBJECTIVE: The experience with MVAC (methotrexate, vinblastine, Adriamycin and cisplatin) chemotherapy in advanced urothelial cancer is reviewed with emphasis on toxicity and efficacy. METHODS: We report on 28 patients with advanced, progressive transitional cell carcinoma (TCC) of the bladder (27) or ureter (1), treated with MVAC. RESULTS: The average number of cycles was 4.5. Leucopenia was the most frequent and severe side effect (18% WHO grade I, 46% GII, 19% GII and 4% GIV). Other side effects were acceptable and could be treated successfully. One patient (complete responder) died of a toxic cause (sepsis), a second patient (partial responder) died of an intestinal bleeding (not drug- or cancer-related). Complete response was seen in 10 patients (36%), partial response and stable disease in 4 patients each (14%), progression in 8 patients (29%), and 2 patients were not evaluable for response. However, relapses were frequent (8 of 12 remaining responders, 66%). Median survival of the whole group was 9 months (0-52), without a significant difference for responders and nonresponders (p = 0.29). CONCLUSION: Our results are comparable to data from the literature with regard to efficacy and toxicity, although detailed toxicity data are unfortunately not always available.

Urological complications in renal transplantation. A comparison between living-related and cadaveric grafts.

OBJECTIVE: Since 1989 the percentage of living-related donor renal transplantations has increased considerably at our institution. We compared the incidence of urological complications in the living-related donor transplantation (LRDT) group and the cadaveric donor transplantation (CDT) group. METHODS: Between September 1989 and September 1994, 534 consecutive patients underwent a renal transplantation. During that period, the percentage of LRDT increased from 10 to 25 (mean: 14.8) per year. In all patients a transvesical ureteroneocystostomy without antireflux mechanism was performed. RESULT: A urological complication developed in 64 (11.9%) of the recipients (obstruction in 6.3%; leakage in 5.6%). In 41 (7.7%) patients the complication was transitory and could be managed with minimal invasive measures such as a percutaneous nephrostomy (n = 34), drainage of a paraurethral fluid collection (n = 13), transurethral bladder drainage (n = 3) or a combination of these. In 23 (4.3%) of the recipients a secondary urological intervention such as a pyeloureterostomy (n = 21) or percutaneous dilatation of a ureteral stricture was necessary. The incidence of obstruction was equal in the LRDT and CDT groups, whereas leakage was more frequently encountered in the LRDT group (11.4 vs. 4.6%, p < 0.05). Transplant survival after 1 year was significantly better in the LRDT group than in the CDT group (97 vs. 77%, p < 0.001). CONCLUSION: The risk of leakage is higher in living-related donor kidney transplantations. Urological complications, however, do not impair graft survival.

Influence of high-intensity focused ultrasound on the development of metastases.

OBJECTIVE: The hypothesis that exposure of a solid tumor to high-intensity focused ultrasound (HIFU) could lead to an increase of metastases was investigated in an animal model. METHODS: The highly metastatic AT-6 Dunning R3327 rat prostate cancer subline was implanted into the hind limb of Fisher-Copenhagen rats and was exposed to 1 pulse/mm2 tumor (acoustical power 1,000 W/cm2) delivered by an experimental machine (Ablatherm, Technomed, France), or the animals were sham treated, as soon as the tumor had reached a volume of 175-225 mm3. The tumor-bearing leg was amputated 24 h later and the number of metastases examined 12 weeks thereafter at autopsy. RESULTS: Metastases were seen in 3 (23%) of the 13 animals exposed to HIFU and in 4 (25%) of the 16 sham-treated animals; this is not significantly different. There was also no significant difference in weight of the lungs that contained metastases between sham-treated and HIFU-treated animals. CONCLUSION: Metastatic spread of animal tumors with a high metastatic potential is not enhanced by HIFU exposure.

Pelvic adenopathy in prostatic and urinary bladder carcinoma: MR imaging with a three-dimensional TI-weighted magnetization-prepared-rapid gradient-echo sequence.

OBJECTIVE: The purpose of this study was to evaluate a magnetization-prepared-rapid gradient-echo (MP-RAGE) sequence as a three-dimensional (3D) T1-weighted MR imaging technique to reveal lymph node metastases from carcinoma of the bladder and the prostate. SUBJECTS AND METHODS: Using a 3D T1-weighted MP-RAGE sequence, MR images of 134 consecutive patients with prostatic carcinoma (n = 63) or urinary bladder carcinoma (n = 71) who were scheduled for radical prostatectomy or radical cystectomy were correlated with histopathologic findings after fine-needle aspiration biopsy (FNAB) (n = 6), open or laparoscopic pelvic lymph node dissection (n = 127), or autopsy (n = 1). MR imaging was used 10 times to guide FNAB in nine patients. RESULTS: The sensitivity, specificity, accuracy, and positive predictive valve of the technique were 75%, 98%, 90%, and 94%, respectively. Thin-slice (1.2-mm) multiplanar reconstructed images correctly revealed diseased nodes in 33 patients. However, MR imaging failed to reveal microscopic metastatic deposits in normally sized nodes in 11 patients. Two other patients had enlarged nodes without metastasis. Furthermore, FNAB guided by MR imaging revealed metastases in six of nine patients. CONCLUSION: MR imaging with a 3D MP-RAGE sequence was accurate in revealing nodal metastases from carcinoma of the prostate and bladder. This imaging technique can be used to select patients for biopsy or laparoscopic pelvic lymph node dissection.

Local staging of prostate cancer with endorectal MR imaging: correlation with histopathology.

OBJECTIVE: To evaluate the accuracy of MR imaging of the prostate with an endorectal surface coil in determining presence, localization, volume, and local stage of prostate carcinoma. SUBJECTS AND METHODS: MR images of 34 patients with biopsy-proven cancer were correlated retrospectively with the histologic mappings of radical prostatectomy specimens. The volume and number of tumor lesions of MR images were calculated and compared with the surgical specimens used as the gold standard. Tumor stage based on MR imaging was compared with the pathologic stage according to the TNM classification. Predictive values were calculated separately for all lesions and for the lesions correctly localized with MR imaging. RESULTS: MR imaging correctly depicted the location of 67% of the tumors. Twenty percent of the lesions depicted by MR imaging appeared to be false-positive errors. The tumors that were missed were located centrally and ventrally in the prostate. Tumor volume as shown by MR imaging was within a 25% range of the actual tumor volume in 10 cases, overestimated in 16 cases, and underestimated in eight cases. Histopathology showed capsular penetration in 12 of 34 patients (35%) and in 14 of 52 lesions (27%). Sensitivity, specificity, and positive predictive values were 43%, 84%, and 55%, respectively. Histologically, capsular penetration extended less than 1 mm into the periprostatic adipose tissue in seven patients. Sensitivity for capsular penetration less than 1 mm was 14%. Sensitivity for capsular penetration more than 1 mm was 71%. Accuracy for differentiating a pT2 from a pT3 tumor was 68%. CONCLUSION: Results from this study indicate that the accuracy of the technique was not satisfactory for predicting actual tumor volume. Tumor detection and localization was more accurate in the peripheral zone than in the central zone. Accuracy was poor for detecting capsular penetration of less than 1 mm, but accuracy was much better for penetration of more than 1 mm. Because recent reports suggest that capsular penetration of less than 1 mm does not adversely affect surgical cure, MR imaging still may be practical in the selection of patients for radical prostatectomy.

The use of 'ultrasensitive' prostate-specific antigen assays in the detection of biochemical recurrence after radical prostatectomy.

OBJECTIVE: To determine the gain in lead time obtained when using ultrasensitive prostate-specific antigen (PSA) assays in the diagnosis of biochemical progression after radical prostatectomy. PATIENTS AND METHODS: The post-operative PSA serum concentrations of 137 patients who had undergone radical prostatectomy were evaluated retrospectively. From these patients, 12 were selected who showed biochemical recurrence, as measured by the Hybritech Tandem-E Singlepoint PSA assay. Samples of the serum frozen at the time of the initial analysis were thawed and PSA values were remeasured by the Abbott IMx PSA assay and the Tandem-E Multipoint PSA assay. Analytical thresholds (zero-dose + 3 SD) for the Tandem-E Singlepoint, IMx and Tandem-E Multipoint assay were 1.0, 0.04 and 0.04 ng/mL, respectively. The lead time to the detection of a recurrence obtained when using the IMx and the Tandem-E Multipoint PSA assay was compared with that attained using the Tandem-E Singlepoint PSA assay. As a control, PSA values were determined in 58 serum specimens of nine patients having no evidence of recurrence after radical prostatectomy. RESULTS: All 58 control specimens had PSA levels below the analytical thresholds of the three assays, except one which had a PSA serum concentration of 0.08 ng/mL, estimated by the IMx assay. When compared with the lead time obtained with the Tandem-E Singlepoint assay, the 12 patients with a biochemical recurrence had a median gain in lead time of 327 days (range 60-627) with the IMx assay and of 369 days (range 60-639) with the Tandem-E Multipoint assay. CONCLUSION: A PSA value > 0.04 ng/mL after radical prostatectomy heralds further biochemical progression. The use of the ultrasensitive IMx and the Tandem-E Multipoint assays provided more lead time, but there is no clear evidence that this gain is necessarily of benefit to the patient.

Update on the Dutch Cooperative Trial: mitomycin versus bacillus Calmette-Guérin-Tice versus bacillus Calmette-Guérin RIVM in the treatment of patients with pTA-pT1 papillary carcinoma and carcinoma in situ of the urinary bladder. Dutch South East Cooperative Urological Group.

Prophylactic intravesical treatment with chemotherapeutic agents or one of the different strains of the immunomodulator bacillus Calmette-Guérin (BCG) reduces tumor recurrence and may prevent progression after transurethral resection (TUR) of superficial bladder cancer. Clinical and pathological prognostic factors are used to categorize different groups at risk for disease recurrence and progression. Solitary low-grade (G1, 2A), low-stage (pTa) tumors have less than a 5% risk of progression, while pT1 G3 tumors with concomitant carcinoma in situ (CIS) have a considerably higher risk of progression and metastases. Thus, prospective clinical trials should consider the different risks associated with different prognostic groups and stratify patients accordingly. The Dutch Cooperative Trial evaluated mitomycin versus BCG-Tice versus BCG-RIVM in 469 patients with pTA/pT1 carcinoma and CIS of the urinary bladder after TUR. Of 437 evaluable patients, 50 had CIS, 254 had pTA tumors, and 133 had pT1 tumors. No statistical differences were observed in toxicity between the two strains of BCG, but local and systemic side effects were more frequent in the BCG groups versus the mitomycin group. No differences in response rate were observed between the 3 treatment groups in patients with CIS. A statistically significant difference in favor of mitomycin was seen, however, in patients with papillary tumors. Mitomycin and BCG-RIVM were equally effective, and mitomycin proved significantly more effective than BCG-Tice. No significant difference in efficacy was observed between the two strains of BCG. Disease recurrence during the study in patients with papillary tumors was seen in 43% of mitomycin-treated patients, 64% of the BCG-Tice group, and 46% of patients treated with BCG-Rivm. However, a subgroup analysis for time to first recurrence for pTa versus pT1 and for grade 1 and 2 versus grade 3 papillary tumors showed no statistically significant between-group difference. Further studies comparing identical regimens, doses, and patient groups are needed to define more clearly which patient groups and tumors are more likely to respond to intravesical therapy.