H. Van Der Poel

Metastasectomy in Renal Cell Carcinoma: A Multicenter Retrospective Analysis

Objective: In 60–70% of patients with renal cell carcinoma (RCC), metastases develop in the course of the disease. In the present analysis, the surgical management of metastases is described, and survival data are presented. This retrospective analysis may help in the management of future cases. Due to the retrospective nature of the data, no comparison between surgical and nonsurgical management is possible. Methods: Between 1985 and 1995, 152 resections of RCC metastases were performed in 101 patients at four Dutch Hospitals. Thirty-five and 6 patients had metastases resected 2 and 3 times, respectively. In most patients, the primary tumor was resected (n = 95). Resections were performed for metastases at different locations: lung n = 54, bone n = 42, lymph nodes n = 18, cerebrum n = 12 and locations in the spinal canal, thyroid, bowel, and testis. Skin excisions were excluded from the analysis. Solitary metastases were resected in 40 patients. Results: Median survival after the initial metastasectomy was 28 months. Initial tumor stage, grade, or size were not related to metastasis location or survival. The number of initially resected pulmonary metastases was of no influence on survival, however, multiple consecutive resections were related with longer survival. Patients with solitary metastases (n = 40) did not show longer survival after the first metastasectomy compared to no solitary lesions. Better survival was found for lung metastases compared to other tumor locations (p = 0.0006, log rank test) and for patients that were clinically tumor free after metastasectomy (p = 0.0230, log rank test). Additional immuno- or radiotherapy did not independently influence survival. Time interval between primary tumor resection and metastasectomy correlated positively with survival: a tumor-free interval of more than 2 years between primary tumor and metastasis was accompanied by a longer disease-specific survival after metastasectomy. Eleven patients were free of disease after metastasectomy with a median time of 47 (14–65) months. The median time of hospital admittance for metastasectomy was 9 days (4–64). Lethal complications were found in 2 patients. Long-term (>5 years) disease-free survival was achieved in 7% of patients whereas 14% of patients were free of disease with a minimal follow-up of 45 months. Conclusions: (1) Surgical management of metastases could be performed with short hospital stay, and low complication rates were found. (2) Disease-free survival was found in 14 and 7%, with follow-ups of at least 45 and 60 months, respectively. (3) The longest survival was found after surgery for pulmonary lesions. (4) Resection of solitary metastases did not result in longer survival compared to resection of nonsolitary lesions. (5) An interval shorter than 2 years between primary tumor and metastases was correlated with a shorter disease-specific survival.

Bladder Wash Cytology, Quantitative Cytology, and the Qualitative BTA Test in Patients with Superficial Bladder Cancer

OBJECTIVES Two new methods for the detection of transitional tumor cells in bladder wash (karyometry: QUANTICYT) and voided urine material (BARD BTA test) were compared with bladder wash cytology for the prediction of histology and tumor recurrence. METHODS Bladder wash material and voided urine were sampled from 138 patients. Bladder wash karyometric (BWK) image analysis and the BTA test were applied. A subsequent urethrocystoscopy was performed and a bladder tumor, when present, was resected. Moreover, each patient was followed for tumor recurrence and progression. RESULTS Sensitivities for the detection of tumors were 34.4%, 44.8%, and 69.0% for the BTA test, bladder wash cytology (BWC), and BWK, respectively (BTA versus BWC, P = 0.64; BTA versus BWK, P = 0.0002; BWC versus BWK, P = 0.0001, using the McNemar test). Specificities for the different tests were 81.3%, 92.5%, and 72.5%, respectively (BTA versus BWC, P = 0.096; BTA versus BWK, P = 0.031; BWC versus BWK, P = 0.001, using the McNemar test). Combinations of tests did not result in better prediction of the presence of tumor. Sensitivity of carcinoma in situ for the three tests was 0 of 3, 3 of 3, and 3 of 3, respectively. Follow-up analysis after a negative cystoscopy revealed comparable predictive values for BWC and BWK. CONCLUSIONS The BTA test may be useful for patients with recurrent, low-grade papillary lesions. However, sensitivity for detection of these lesions, although higher than that for BWC, was only 42.9%. The highest specificity was found for BWC; however, this was accompanied by the lowest sensitivity of all three tests. The lower specificity of BWK was accompanied by a better prediction of tumor recurrence after a normal urethrocystoscopy. BWK is particularly sensitive for the recurrence of high-grade bladder lesions.

Comparison of surveillance and retroperitoneal lymph node dissection in Stage I nonseminomatous germ cell tumors

OBJECTIVES To compare retrospectively the treatment results of surveillance and primary retroperitoneal lymph node dissection (RPLND) of patients with clinical Stage I nonseminomatous germ cell tumors of the testis (NSGCT) in two institutions in The Netherlands. METHODS From 1982 to 1994, 90 consecutive patients with clinical Stage I NSGCT were prospectively entered in a surveillance protocol in Amsterdam (group 1). In the same period, 101 patients with clinical Stage I NSGCT underwent primary RPLND in Nijmegen (group 2). Both patient populations were comparable for patient age, presence of vascular invasion, and embryonal cell components in the primary tumor. All patients in group 1 with relapse, except for 2, were treated with cisplatin-based chemotherapy. All patients in group 2 with vital tumor in the RPLND specimen were treated with two adjuvant courses of combined chemotherapy (cisplatin, etoposide, and bleomycin). RESULTS In group 1, at a median follow-up of 7.7 years, 23 patients (26%) had relapse. The median time to relapse was 12 months. Relapses were located retroperitoneally (n = 18, 78%), in the lung (n = 3, 13%), scrotally (n = 1, 4%), and combined in the liver, lung, and pleura (n = 1, 4%). After treatment of relapses (chemotherapy in 21 and/or surgery in 11), only 1 patient died of disseminated disease. A disease-free survival rate of 98.5% was achieved at the median follow-up. The main toxicities consisted of short-lasting leukopenia, accompanied by infection (13%). Four patients reported cardiovascular and four neuropathy complaints. In group 2, the median follow-up was 6.9 years. In 31 patients (30.7%), vital tumor was found retroperitoneally; after two courses of combined chemotherapy, none of them had a relapse. Seven patients with pathologic Stage I disease (6.4%) had a pulmonary relapse within 1 year after surgery. No retroperitoneal relapses were found. After chemotherapy, 6 patients with relapse were salvaged, and 1 died of disseminated disease. The disease-specific survival rate in group 2 was 98% at the median follow-up. The most frequent surgical complications were lymphocele (n = 3), small bowel obstruction (n = 3), and abdominal pain (n = 3). The antegrade ejaculation rate was 94%. CONCLUSIONS Excellent treatment results in terms of disease-free survival can be achieved in Stage I NSGCT with both surveillance and primary RPLND. Patients with pathologic Stage II disease adjuvantly treated with chemotherapy did not have any relapse and consequently all survived. Most complications after both treatment strategies are reversible. The choice of treatment should be based on balanced information and not on dogmatic principles.

A retrospective study of high mobility group protein I(Y) as progression marker for prostate cancer determined by in situ hybridization

In a previous study using RNA in situ hybridisation (RISH), we found a significant correlation between high mobility group protein I/Y, [HMG-I(Y)] mRNA expression and tumour stage and grade in prostate cancer patients, suggesting that HMG-I(Y) might be a potential prognostic marker in prostate cancer. However, our clinical follow-up was limited because cryopreserved material was used. Assessing the potential prognostic value of this molecule is of importance because the clinical course of prostate cancer patients remains unpredictable. Here we describe our results on paraffin-embedded archival material from a group of 102 patients undergoing radical prostatectomy. These were evaluated for the presence of HMG-I(Y) using RISH, and a follow-up of 12-92 months (average 53 months) was available. In 2 of 14 prostate cancers in which the predominant histological pattern was of Gleason grade 1-2, a high HMG-I(Y) expression was observed, whereas in 19 of 23 Gleason grade 3, and 34 of 35 Gleason grade 4-5 tumours, high HMG-I(Y) mRNA levels were detected (chi-square = 38.78, P < 0.0001). Moreover, of tumours that expressed high HMG-I(Y) levels, 25% were organ confined (T1-2), in contrast to 74.5% of the invading tumours (T3, chi-square = 15.8, P < 0.001). Furthermore, 87% of recurrent tumours showed high HMG-I(Y) expression. However, a multivariate regression analysis including Gleason grade, clinical tumour stage, HMG-I(Y) expression and prostate-specific antigen (PSA) levels showed Gleason grade as the most accurate predictor of progression. High HMG-I(Y) levels measured by RISH were indicative of a worse prognosis, albeit that additional value over the more subjective grading methods was not evident.

Urinary NMP22TM and Karyometry in the Diagnosis and Follow-Up of Patients with Superficial Bladder Cancer

Objective: To study the value of two outpatient urine tests with regard to the diagnosis and recurrence of bladder tumors. Methods: Fifty patients with a history of superficial bladder cancer were evaluated with urinary NMP22TM levels (cutoff level 10 U/ml), bladder wash karyometry (low versus intermediate and high risk) and cystoscopy. All patients were followed for 1 year. Results: Diagnostic negative and positive predictive values (NPV and PPV) of the tests were, respectively: NMP22 91.2 and 56.3%, and karyometry 80 and 33.3%. Prognostic NPV and PPV with regard to a subsequent recurrence were, respectively: NMP22 77.8 and 27.3%, and karyometry 82.6 and 50%. Conclusion: The diagnostic value of NMP22 is good. Since the 3 false-negative results were in low-stage and low-grade lesions, this test could be used as a prescreening for cystoscopy. The NPV of these tests with regard to tumor recurrence is around 80%, but only karyometry has a significant PPV. Change in the follow-up policy on the basis of these tests remains difficult. In patients with neobladders NMP22 appears to be of little use, because of the high urinary NMP22 levels in the absence of malignancy.

Role of Extent of Fascia Preservation and Erectile Function After Robot-assisted Laparoscopic Prostatectomy

OBJECTIVES To test a simple intraoperative scoring system for the circumferential extent of fascia preservation (FP) for the prediction of postoperative erectile function. With the advent of robotic and endoscopic surgery for prostate cancer, more extensive FP has emerged as a method to improve postoperative erectile function. METHODS A total of 107 consecutive cases with normal preoperative erectile function were treated using robot-assisted laparoscopic prostatectomy for localized prostate cancer. The erectile, sexual, and global quality of life outcomes using the European Organization for Research and Treatment and Cancer Quality of Life questionnaire-C30 and prostate cancer-specific 25-item questionnaire were assessed at 6 months postoperatively. RESULTS At 6 months postoperatively, 57 men (53%) reported no or minimal effects on erectile function with or without the use of a phosphodiesterase type 5 inhibitor. The patient age at surgery, prostate size, and FP score were associated with erectile function at 6 months postoperatively. The mean FP score was 9.2 +/- 2.8 and 4.7 +/- 2.4 for patients without and with erectile dysfunction postoperatively, respectively. On multivariate analysis, the FP score and patient age at surgery were the best predictors of postoperative erectile function. No correlation between the FP score and positive surgical resection margin rate was observed. A greater FP score predicted for greater questionnaire-based libido, sexual activity, and sexual function scores. CONCLUSIONS A scoring system for the extent of circumferential FP during prostatectomy is a stronger predictor of postoperative erectile function recovery than is laterality (bilateral or unilateral) or fascial depth (interfascial or intrafascial). More ventral FP significantly contributed to postoperative erectile function recovery.

The Bard® BTA Test: Its Mode of Action, Sensitivity and Specificity, Compared to Cytology of Voided Urine, in the Diagnosis of Superficial Bladder Cancer

Objectives: Application of immunocytology directed against antigens of urothelial tumor cells or tumor-associated breakdown products intends to improve the sensitivity of the diagnosis of superficial transitional cell carcinoma (TCC) of the urinary bladder. In this study, the mode of action, sensitivity and specificity of the Bard® BTA test, detecting a tumor-associated release of a basement membrane complex, was addressed and compared with voided urine cytology (VUC). Results: Contrary to grade, a significant (p = 0.003) relationship between tumor stage and BTA test sensitivity was observed, being 23.8, 33.3 to 100% for Ta (n = 42), T1 (n = 6) to ≥T2 (n = 5), respectively. These data suggest an association between an increase of the BTA test sensitivity with an increase of basement membrane degradation or interruption. With regard to this mechanism, the BTA test may be of special importance for monitoring tumor progression or increase in tumor invasiveness. Detection of low-stage, low-grade tumors by noninvasive techniques remains a challenge. The sensitivity of the BTA test for the presence of TCC was 32.3%, while that of VUC was 17.7%, but in this study the difference was not statistically significant. Furthermore, the BTA test was not more effective in identifying the various tumor grades, stages or stage/grade groupings. However, dividing the patients in two groups of low risk (TaG1/TaG2) and high risk (TaG3 to ≥T2) leads to a significant (p = 0.008) increased sensitivity of the BTA test (27.3%) in detecting patients with low-risk tumors compared to VUC (3.0%). The specificity of the BTA test in patients with a history of TCC was 81.6%, while that of VUC was 98.9%. Conclusion: The sensitivity of the BTA test is at least equivalent to VUC and may be suited to monitor increase in stage in patients suffering from bladder carcinoma, but cannot replace cystoscopy in patients suspected for a bladder tumor.

Quanticyt: Karyometric analysis of bladder washing for patients with superficial bladder cancer

OBJECTIVES Quantitative cytology by image-analysis techniques enables objective interpretation of nuclear features in light microscopic images. QUANTICYT, a quantitative karyometric cytology system, was used in the follow-up of patients with superficial bladder cancer. METHODS From 1992 to 1995, 4137 samples from 1412 patients were obtained. At 1-year follow-up after the initial bladder washing, a tumor recurrence rate of 21% was found. In this period, tumor progression to invasive disease occurred in 1.6% of patients. Scoring of tumor by the QUANTICYT system was based on two nuclear features: the 2c deviation index and the mean of a nuclear shape feature: MPASS. RESULTS The method was found to be reproducible and superior to visual cytologic interpretation. QUANTICYT analysis of the bladder washings resulted in a score of low, intermediate, and high risk. In a multivariate analysis, highest grade of earlier tumor and QUANTICYT risk score were the best predictors of tumor recurrence and progression. For the easy application of QUANTICYT analysis in daily routine, a report form that included patient history and DNA histogram was developed. CONCLUSIONS QUANTICYT karyometric analysis of bladder-wash material proved a useful, clinically applicable grading tool in the follow-up of patients with superficial bladder cancer, with sufficient power to be used in decision-making in the individual patient.

Laparoscopic Sentinel Lymph Node Biopsy for Prostate Cancer: The Relevance of Locations Outside the Extended Dissection Area

Objective. To assess the relevance of sentinel lymph nodes (SNs) outside the extended pelvic lymph node dissection area (e-PLND). Patients and Methods. Evaluation of our laparoscopic SN procedures for prostate cancer patients of intermediate prognosis. Retrospective data collection on the exact location of the excised SNs and the pathology results were analyzed. Results and Limitations. Of the 121 patients, 49 had positive lymph nodes. 37 patients (31%) had SNs outside the e-PLND template. Five of these nodes were tumor bearing but only twice exclusively so. Of the 14 patients considered for salvage treatment, 6 were node positive. 7 of these 14 patients (50%) had SNs outside the extended dissection area, yet none of these nodes were tumor positive. Limitations are those of a retrospective study. Conclusions. Laparoscopic SN biopsy may show SNs outside the e-PLND template in 31% of the patients. However, nodes that are exclusively positive in one of these areas are rare. For the dichotomy positive or negative nodes, the locations outside the e-PLND area are not often relevant. Nevertheless, when all positive nodes are to be treated by resection or radiotherapy, these locations are relevant. When considering salvage treatment for prostate cancer, the method is feasible.

A trial of consent procedures for future research with clinically derived biological samples

Background:The aims of this study were to determine which consent procedure patients prefer for use of stored tissue for research purposes and what the effects of consent procedures on actual consenting behaviour are.Methods:We offered 264 cancer patients three different consent procedures: ‘one-time general consent’ (asked written informed consent), ‘opt-out plus’ (had the opportunity to opt out by a form), or the standard hospital procedure (control group). The two intervention groups received a specific leaflet about research with residual tissue and verbal information. The control group only received a general hospital leaflet including opt-out information, which is the procedure currently in use. Subsequently, all patients received a questionnaire to examine their preferences for consent procedures.Results:In all, 99% of patients consented to research with their residual tissue. In the ‘one-time consent’ group 85% sent back their consent form. Patients preferred ‘opt-out plus’ (43%) above ‘one-time consent’ (34%) or ‘opt-out’ (16%), whereas 8% indicated that they did not need to receive information about research with residual tissues or be given the opportunity to make a choice.Conclusions:The ‘opt-out plus’ procedure, which places fewer demands on administrative resources than ‘one-time consent’, can also address the information needs of patients.