Polymorphisms of human estrogen receptor (ER) gene alpha and beta in prostate cancer PC-EW and PC-OR cell lines.

BACKGROUND: Prostate cancer is the second leading cause of death among men in Western countries. Genetic alterations of the estrogen receptor gene are known to be indicative of a higher risk of this disease. The estrogen receptor gene is found as two subtypes, alpha and beta. In this study the estrogen receptor alpha and beta genes were tested in 2 human prostate cancer cell lines: the hormone-sensitive PC-EW and the hormone-independent PC-OR. MATERIALS AND METHODS: Genomic DNA was isolated from 2 cell lines from metastatic prostate adenocarcinoma in hetero-transplanted male athymic nude (nu/nu) Balb/c mice. Mutation screening was performed by sequencing of exons 1-8 and intron 1 of the human estrogen receptor gene alpha, and exons 1-9 of estrogen receptor gene beta. RESULTS: No point mutations were detected in the ER gene subtypes of either cell line. Polymorphisms were found of ER-alpha in exon 1, intron 1, exon 3, 4, 5, intron 6 and exon 8 and of ER-beta in intron 2 and exon 9. CONCLUSION: Point mutations of ER-alpha and -beta are not necessary for metastatic prostate cancer, alterations in different areas of the ER genes are more often found. These polymorphisms are a part of many genetic influences that accumulate to contribute to men's overall risk for developing prostate cancer.

[Pasqualini's syndrome]. / Pasqualini-Syndrom.

INTRODUCTION: Pasqualini's syndrome is an isolated, incretory functional disorder of the testes with a secondary Leydig cell insufficiency but, unlike Klinefelder's syndrome, with normal spermiogenesis and fertility. This unusual form of hypogonadism is caused by an inherent LH secretion disorder of the pituitary gland. The result of this is the secondary Leydig cell insufficiency and a corresponding peripheral androgen deficiency. In this communication we present the case of a 67-year-old man with Pasqualini's syndrome and a histologically confirmed left seminoma. In view of the current lack of data and our experience, we describe the properties of this uncommon syndrome; therapy, prognosis and possible relationship with seminoma are discussed in more detail. CASE REPORT: The 67-year-old male presented in our outpatient department with the urgent suspicion of a left testicular tumour as a painless swelling of the testis since about three months. In the case history we found a previously diagnosed hypogonadotropic hypogonadism, which is described in the literature as the so-called Pasqualini syndrome. On palpation, the left testis was about fist-size, scirrhous, mildly pressure sensitive and highly suspicious. Sonography of the testes revealed the enlarged left testis to be completely inhomogeneous with hypo- and hyperdense areas and large spatial requirements with unremarkable perfusion. On the basis of the clinically and sonographically supported diagnosis of a tumour of the left testis and inguinal exposure of the testes was performed. Intraoperative histology of a sample confirmed the diagnosis of a testicular tumour in the sense of a seminoma. A high left ablatio testis was carried out. DISCUSSION: The occurrence of testicular tumours of the seminoma type in association with Pasqualini's syndrome has not previously been described in the literature. Thus, we assume that the seminoma had occurred at this age independently of the Pasqualini syndrome. For the treatment of Pasqualini's syndrome not only hCG but also testosterone have been employed with success. The patient must continue therapy for his whole life. The results of interruption tests confirm that it is not a passing ailment but rather a persisting, endogenous disease. PRACTICAL CONCLUSIONS: Since the molecular genetics and genesis of this disease have not been clarified unambiguously, further clinical and experimental studies are necessary in order to better understand the disease. An increased risk of testicular tumours has not yet been observed on account of the small number of cases of Pasqualini's syndrome.

[Wilms' tumors in adults]. / Wilms-Tumoren im Erwachsenenalter.

Wilms' tumors develop from persistent, primitive metanephrogenic stem cells. Their biology and etiology in adults is still unknown even though remnants of primitive metanephrogenic tissue, which tends to malignancy, is suspected, and there are very few scientific studies on the biology of Wilms' tumors in adults. Such a tumor occurs at a rate of 0.2/million adults in Europe and the USA. In this article, we describe the course of the disease in two adults with histologically confirmed Wilms' tumors. Both patients underwent a radical nephrectomy followed by chemotherapy as indicated by the SIOP nephroblastoma study.

[Urethral duplication in a male child. Accessory urethra with a normotopic opening in a penopubic epispadias with dorsal penis deviation]. / Urethraduplikatur beim männlichen Kind. Akzessorische Harnröhre mit normotoper Mündung bei penopubischer Epispadie mit dorsaler Penisdeviation.

Urethral duplication is a rare deformity which can present in various forms, commonly together with other congenital malformations. The embryological genesis is unknown. The isolated deformity is most often found in young males, while for young females it is very rare. We report the case of a 1.5 year old male child having a duplicate urethra with penopubic epispadias and dorsal penis deviation. The child, with known penopubic epispadias grade II and dorsal penis deviation, presented for pediatric urological consultation involving additional diagnostics and therapy. Examination revealed a penopubic epispadias with an external urethral exit at the base of the penis. A preoperative micturating cystogram led to the diagnosis of an accessory central as well as an epispadic urethra. We then carried out urethral reconstruction with the surgical combination of both urethras into a single functioning unit. The penis deviation was corrected after Ransley in the same operation. The postoperative course and aftercare showed normal micturition with a normotopic urethral entry as well as a good urine stream without evidence of a stricture or residual urine. An duplicate urethra is an uncommon malformation which is, however, found more often in male patients. Surgery is based on the individual and must be planned dependent on the morphology present. In all cases, both functional and cosmetic aspects must be taken into account.

[Endometriosis of the ureter and urinary bladder]. / Endometriose von Ureter und Harnblase.

Endometriosis is a benign growth of ectopic endometrial mucous membrane which has maintained the histological characteristics and biological reactions of uterine mucous membrane. In only 1-2% of cases does it occur in the urinary system, most commonly in the urinary bladder. Such an endometriosis is often diagnosed very late due both to its commonly asymptomatic course and its rarity. Individual therapy is dependent on the age of the patient, the wish for children and the extent of the growth. For endometriosis covering a large area, surgery is recommended. Methods of choice are laparoscopic bladder resection for the urinary bladder, ureterocystoneostomy using the Psoas hitch for the distal ureter, end to end anastomosis or endoscopic incision for short, proximal cases, and for extended areas, ileum cross-bridge attachment or kidney mobilization using nephropexy.

[Frasier syndrome: a rare syndrome with WT1 gene mutation in pediatric urology]. / Frasier-Syndrom: Ein seltenes Syndrom mit WT1-Genmutation in der Kinderurologie.

INTRODUCTION: Frasier syndrom is an autosomal dominant, hereditary disease characterized by nephropathy, gonadal dysgenesis and risk of gonadal blastoma in early childhood. To date, in many patients with Frasier syndrome WT1 mutations have been found, occurring exclusively as germ-line mutations of the alternative splicing donor site in intron 9. A Wilms tumor is seen only rarely in this clinical entity. In the present paper we describe the clinical course of a patient with Frasier syndrome confirmed by molecular genetic analysis. CASE REPORT: Our patient with Frasier syndrome as confirmed by molecular genetic analysis is now 19 years old. The patient became dependent on dialysis due to nethropathy in the form of focal sclerosing glomerulonephritis and terminal renal insufficiency. A kidney transplantation in the left iliac fossa together with new implantation of the ureter according to Dodson. For prophylactic reasons on account of the high risk of gonadal blastoma associated with the disease and sonographically detected microlithiasis in both testicles we performed one year later an inguinal castration. Histology revealed the picture of a severe tubular testicular atrophy with arrested spermatogenesis and focal intratubular germ-line neoplasia. CONCLUSIONS: This case report shows that, besides our already published series with Denys-Drash syndrome, WT1 mutations may also be associated with the so-called Frasier syndrome. For children with Frasier syndrome confirmed by molecular genetic analysis and loss of function of the testicles, we recommend performance of a prophylactic castration. We also suggest that phenotypical female patients with focal sclerosing glomerulonephritis be examined for WT1 mutations.

A complex case of megalourethra and its repair.

Megalourethra is a rare malformation of the urethra caused by a lack of corpus sponigosum and in some cases corpora cavernosa in the region of the distal urethra. The absence of these structures causes a ballooning of the urethra despite there being no mechanical obstruction. A male child presented with so-called fusiform megalourethra, with absence of the corpora cavernosa and urethral duplication. A voiding cystourethrogram was used to diagnose a fusiform megalourethra with pronounced meatal stenosis and extreme stenosis of pendulous urethra. In addition, there was urethral duplication in the form of an accessory urethra stretching from the urethral colliculus to the perineum. Absence of the corpora cavernosa was also suspected in the distal urethra. The surgical procedure involved pendulous urethroplasty with an onlay technique using urethral duplication and penile reduction. This method of treating megalourethra has not been previously reported. The operative technique for fusiform megalourethra with genital malformation has to be tailored to each individual case, depending on the intraoperative and endoscopic findings.

[Retroperitoneal ganglioneuroma]. / Retroperitoneales Ganglioneurom -- Darstellung eines benignen Neuroblastoms.

The ganglioneuroma is a benign neuroblastal tumor. All neuroblastomas and ganglioneuromas derive from immature cells of the sympathetic nerve system. The ganglioneuroma is a very rare disease and effects newborns and infants more often than adolescents and adults. The benign tumors are relatively difficult to diagnose since they usually are asymptomatic. A 5-year old girl with persistent bladder wall thickening and prominent course of the prevesical ureter presents for diagnosis and therapy. Sonography demonstrated a space-occupying lesion of the left kidney. Subsequent MRI raises the suspicion of a retroperitoneal neuroblastoma. The tumor could be removed in two surgical sessions. The ganglioneuroma is a benign tumor with symptoms depending on location and with a relatively good prognosis. Its low incidence and resultant limited experience often leads to delayed diagnosis, potentially determining therapy and diagnosis.

Does the distance to normal renal parenchyma (DTNRP) in nephron-sparing surgery for renal cell carcinoma have an effect on survival?

BACKGROUND: The effect of the distance to normal renal parenchyma (DTNRP) on survival after nephron-sparing surgery (NSS) for renal cell cancer (RCC) was analyzed. Additionally, the role of T-classification, tumor diameter and tumor grading was considered. PATIENTS AND METHODS: NSS was performed on 126 patients with RCC between 1988 and 2000. Eighty-six patients were submitted to annual follow-up. These 86 patients were sub-classified into statistical groups according to the distance to normal renal parenchyma (< or = 2mm; > 2mm - < or = 5mm; >5 mm), T-classification, tumor diameter (< or = 20mm; > 20mm - < or = 30 mm; >30 mm - < or = 50mm; > 50mm) and tumor grading. The effect of belonging to one of these groups on survival was analyzed using the Log-Rank-Test (SPSS; version 11.0) and the Kaplan and Meier survival data. The level of significance was set at p < 0.05. RESULTS: During the follow-up period, 4 patients died related to RCC and 15 patients died from other causes. The tumor-specific survival was 95.4%. At the end of 2002, the mean follow-up time was 5.5 years (range 0.1 - 14.7). None of the variables which had been analyzed in our statistical groups had an effect on the overall survival. CONCLUSION: The distance to normal renal parenchyma does not influence survival, suggesting an additional resection to be unnecessary even in cases where the DTNRP is reported by frozen section to be less than 2 mm. RCC up to 5 cn in tumor diameter can be safely removed by NSS, even in the presence of a functional intact contralateral kidney.

Radiochemotherapy after transurethral resection is an effective treatment method in T1G3 bladder cancer.

AIM: Conservative therapy using deep transurethral resection (TUR) followed by radiochemotherapy is a novel treatment strategy in stage TI grade 3 (TIG3) transitional cell carcinoma (TCC) of the bladder. The aim of this study was to present our long-term results of radiochemotherapy in T1G3 TCC patients. MATERIALS AND METHODS: A total of 64 patients with TIG3 TCC of the bladder underwent a TUR and a subsequent radiochemotherapy protocol at our institution. Following TUR, a median dose of 55.8 (range; 45-69.4) Gy radiation therapy was applied to the bladder, and simultaneous chemotherapy was initiated using cisplatin, carboplatin and/or 5-fluorouracil. After completion of the protocol, response was evaluated by repeat TUR, and check cystoscopies were performed at regular intervals. Median patient age was 66 (range; 30-82) years and median follow-up was 43.2 (range; 6-127) months. RESULTS: Complete response was achieved in 55 (90.2%) patients. Of the complete responders, 7 patients experienced a superficial (Ta, T1) recurrence and 8 patients had progression. In 8 patients with refractory superficial and invasive relapses, a salvage cystectomy was mandated. The overall progression rate was 14%. The overall and disease-free survival rates were 76% and 93%, respectively at 5 years. During followup, 4 patients suffered from reduced bladder capacity, and 2 patients underwent cystectomy due to shrinking bladder. CONCLUSION: Combined multimodality therapy is a safe and curative treatment option for patients with T1G3 TCC of the bladder in the hands of dedicated multimodality teams. Therefore, it is reasonable to justify radiochemotherapy combined with TUR in the first-line treatment of T1G3 tumors.

[Xanthogranulomatous pyelonephritis: presentation of an unusual case]. / Xanthogranulomatöse Pyelonephritis: Präsentation eines ungewöhnlichen Falles.

INTRODUCTION: Xanthogranulomatous pyelonephritis is a morphologically and clinically unique manifestation of chronic pyelonephritis with the formation of pus or granulomas. The most frequent predisposing factors for the development of xanthogranulomatous pyelonephritis are urinary obstruction (e. g., stones, tumors, congenital anomalies and functional impairment) and infection of the collecting system. CASE REPORT: We describe a 2-year-old female patient with unclear abdominal complaints, diarrhea, malaise, loss of appetite, weight loss, pale skin color, and recurrent and undulating fever in the presence of known left nephrolithiasis. Based on the clinical examination and imaging, above all, CT, the presumptive diagnosis of xanthogranulomatous pyelonephritis of the left kidney was made. A left lumbar nephrectomy was performed and histology confirmed the diagnosis. CONCLUSION: Xanthogranulomatous pyelonephritis is a relatively rare entity that is associated with obstruction (e. g., stones) and infection of the urinary tract. Its rarity and resultant unfamiliarity often delay diagnosis and therapy, which in turn affect the prognosis. Furthermore, this entity can be mistaken for renal tumors (renal cell carcinoma and Wilms tumor), but nowadays this should be mostly eliminated with the advances in the imaging methods.

[Denys-Drash syndrome. Experience gathered in Erlangen illustrated by two case reports]. / Denys-Drash-Syndrom. Erlanger Erfahrungen am Beispiel zweier Fallberichte.

Denys-Drash syndrome is a rare symptom complex associated with obligatory childhood nephrotic syndrome, male pseudohermaphroditism, and Wilms' tumor. The etiology of Denys-Drash syndrome is attributed to a mutation of the WT1 gene. We report on two cases of Deny-Drash syndrome confirmed by genetic testing. Rapidly evolving terminal renal insufficiency was detected in both patients necessitating bilateral nephrectomies with prophylactic intent. In one of the patients, a Wilms' tumor had already been verified in one kidney so that chemotherapy had to be initiated.The risk of Wilms' tumor is very high in patients with a WT1 mutation, which leads to the need for removal of both kidneys during or before transplantation. It would be important to perform a diagnostic work-up for WT1 gene mutation in children who develop renal failure in the 1st year of life.

Radiochemotherapy in locally invasive non-metastatic carcinoma of the bladder.

We therefore believe that our therapeutic concept is a true alternative to primary cystectomy, with comparable survival rates. We observed a high rate of functional organ preservation in long-term survivors (79% with complete remission (CR) after 5 years). Radiation bladders were rare at doses not exceeding 60 Gy. Age and co-morbidity were not exclusion criteria. Presence of a competent and cooperative radiotherapy department is a precondition to preventing akinetic radiation bladders. Continuous life-long follow-up is necessary. Cystectomy, together with modern urinary diversions, is still necessary; it is performed in non-responders and in patients with muscle-invasive recurrences.

Epidermal growth factor receptor and g250: useful target antigens for antibody mediated cellular cytotoxicity against renal cell carcinoma?

PURPOSE: Monoclonal antibodies are a novel treatment option for certain tumor patients. We evaluated the potential of antibody derivatives against epidermal growth factor receptor and G250, which are 2 candidate antigens on renal cell carcinoma, to recruit effector cells for killing renal cell carcinoma. MATERIAL AND METHODS: As a measure of cytotoxicity, 51chromium release assays against renal cell carcinoma lines were performed using unseparated blood or isolated cell populations as the source of effectors. Blood was obtained from healthy donors, or from patients receiving granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor for enhancing effector cell function. Parental human IgG1 antibodies against epidermal growth factor receptor and G250 were compared with respective chemically linked bispecific antibodies targeting IgA Fc receptor FcalphaRI (CD89), a novel cytotoxic trigger molecule on polymorphonuclear cells and monocytes/macrophages, which were constructed by chemically crosslinking appropriate F(ab') fragments. RESULTS: Renal cell carcinoma lines were highly resistant to complement dependent lysis. With mononuclear effector cells high levels of renal cell carcinoma killing were observed with a humanized epidermal growth factor receptor directed monoclonal antibody, while the same antibody did not recruit granulocytes (polymorphonuclear cells) for antibody dependent cell mediated cytotoxicity. However, polymorphonuclear cells effectively lysed renal cell carcinoma with [FcalphaRI x epidermal growth factor receptor] bispecific antibody. FcalphaRI mediated killing was significantly enhanced when the blood of patients on granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor therapy was analyzed. However, G250 mediated only low levels of killing with mononuclear cell but not with polymorphonuclear effector cells. CONCLUSIONS: Targeting epidermal growth factor receptor proved to recruit efficiently mononuclear or polymorphonuclear cell mediated killing mechanisms, while G250 directed antibody constructs were significantly less effective. Particularly effective renal cell carcinoma killing was observed with combined [FcalphaRI x epidermal growth factor receptor] bispecific antibody and granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor.

Vardenafil increases penile rigidity and tumescence in men with erectile dysfunction after a single oral dose.

OBJECTIVES: To evaluate the effect of two doses of vardenafil hydrochloride on penile rigidity and tumescence while determining the pharmacokinetics. METHODS: Twenty-one patients with erectile dysfunction completed three oral single-dose regimens (placebo, 20 and 40 mg vardenafil) in a randomized, placebo-controlled, 3-way cross-over study. Penile rigidity and tumescence were measured at the base and tip with a Rigiscan for up to 2 h after dosing. The period included three 20-min repeated episodes of visual sexual stimulation. Blood samples were taken periodically up to 24 h after dosing. RESULTS: After 20 and 40 mg vardenafil, the mean duration of >60% rigidity of the base of the penis was greater than after placebo by 42.9 min (95% Cl 29.3-56.4) and by 49.3 min (95% Cl 35.7-62.9), respectively (p<0.001), and greater than after placebo by 34.6 min (95% Cl 22.1-47.1) for both doses at the tip. Additionally, significantly greater rigidity activity units and tumescence activity units were found for both doses compared with placebo (p<0.001). The plasma concentrations of vardenafil increased rapidly, with a median t(max) of about 40 min and a mean t1/2 of 4.4-4.8 h. Relative bioavailability was slightly higher for the 40-mg dose than for the 20-mg dose. The treatments were well tolerated, although slightly more adverse events, primarily headache, flushing and nasal congestion, were seen with the 40-mg dose compared with placebo. CONCLUSION: The findings confirm that vardenafil was able to generate stronger erections of longer duration than placebo under conditions of visual sexual stimulation in patients with erectile dysfunction. The pharmacokinetic, pharmacodynamic and tolerability profiles support vardenafil hydrochloride as a strong candidate for further testing as a treatment for erectile dysfunction.

Bladder preservation in muscle-invasive bladder cancer by conservative surgery and radiochemotherapy.

Organ preservation has been investigated in muscle-invasive bladder cancer over the past decades as an alternative to standard radical cystectomy. The results of large prospective protocols and population-based studies suggest that an organ-preserving approach is possible without deferring the survival probability. Organ preservation requires a trimodal schedule, including transurethral surgery (transurethral resection of bladder tumor (TURBT)), radiation, and chemotherapy. A complete TURBT is the most important single prognostic factor, and should be attempted. Radiotherapy, in conjunction with concurrent platinum-based chemotherapy, can control the vast majority of urothelial bladder tumors. The histologically-proven complete remission rates of macroscopic tumors (unresectable by TURBT) lie in the range of about 70%. After radiochemotherapy, a histological response evaluation with repeated TURBT is recommended. Patients with residual tumor require salvage cystectomy. In cases of complete remission, patients can maintain their bladders but they should be closely followed over years. The risk of severe late-radiation sequelae is low, in the range of less than 5%. About 75% of long-term survivors maintain a normally functioning bladder.

Radiotherapy is an effective treatment for high-risk T1-bladder cancer.

PURPOSE: Current treatment options for high-risk superficial T1-bladder cancer (Grade 3, associated Tis, multifocality, tumor diameter > 5 cm or multiple recurrences) include early cystectomy or the goal of organ preservation by adjuvant intravesical therapy after transurethral resection (TURB). We have evaluated the efficacy of adjuvant radiotherapy or radiochemotherapy on local control, bladder preservation, recurrence rate and long-term survival after TURB of high-risk T1-bladder cancer. PATIENTS AND METHODS: From May 1982 to May 1999, a total of 74 patients with T1-bladder cancer were treated by either radiotherapy (n = 17) or concomitant radiochemotherapy (n = 57) after TURB. Radiotherapy was initiated 4 to 8 weeks after TURB; a median dose of 54 (range: 45 to 60) Gy was applied to the bladder with daily fractions of 1.8 to 2.0 Gy. Since 1985 chemotherapy has been given in the 1st and 5th week of radiotherapy and consisted of cisplatin (25 mg/m2/d) in 33 patients, carboplatin (65 mg/m2/d) was administered in 14 patients with decreased creatine clearance (< 50 ml/min). Since 1993 a combination of cisplatin (20 mg/m2/d) and 5-fluorouracil (600 mg/m2/d) was applied to 10 patients. Salvage cystectomy was recommended for patients with refractory disease or invasive recurrences. At the time of analysis, the median follow-up for surviving patients was 57 (range: 3 to 174) months. RESULTS: After radiotherapy/radiochemotherapy, a complete remission at restaging TURB was achieved in 62 patients (83.7%), 35 of whom (47% with regard to the total cohort of the 74 treated patients) have been continuously free of tumor, 11 patients (18%) experienced a superficial relapse and 16 patients (26%) showed tumor progression after initial complete response. Overall-survival was 72% at 5 years and 50% at 10 years with 77% of the surviving patients maintaining their own bladder at 5 years. Negative prognostic factors for cancer-specific survival were non-complete (R1/2) initial TURB (p = 0.12) and recurrent disease (p = 0.07); combined radiochemotherapy was more effective than radiotherapy alone (p = 0.1). CONCLUSION: Adjuvant radiotherapy/radiochemotherapy offers an additional option in high-risk superficial bladder cancer with a high chance of cure and bladder preservation. The ultimate value of radiotherapy in comparison with other treatment options should be determined in randomized trials.

Androgen receptor gene mutations do not occur in ovarian cancer.

Genetic alterations have been frequently found in ovarian cancer. There is some indirect evidence indicating that mutation of the steroid receptor genes may play a role in the carcinogenesis of ovarian cancer. Human androgen receptor (hAR) gene mutations have been found in up to 50% of hormone-relapsed prostate cancer. The role of hAR mutation and its association with decreased expression in ovarian cancer has never been elucidated. In this study mutations of hAR gene in 38 human ovarian cancer cell lines with different AR expression pattern were studied using SSCP. No mutation of the hAR gene was found. Mutation of hAR gene is an infrequent event and therefore unlikely to be involved in the development of ovarian cancer. The decreased expression of hAR in advanced ovarian tumor is not due to genetic aberration of hAR. Mutation screening of hAR may not provide any information for risk assessment of developing ovarian cancer.

Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma: possible predictors for response to radiochemotherapy and successful bladder preservation.

PURPOSE: Several groups have reported the value of bladder preservation by a combined treatment protocol, including transurethral resection (TUR-B) and radiochemotherapy (RCT). As more experience is acquired with organ-sparing treatment, patient selection should be optimized. The purpose of this study was to investigate the role of several biologic markers that may predict response to RCT in muscle-invasive bladder carcinoma. METHODS AND MATERIALS: The apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 70 patients treated for invasive bladder cancer by TUR-B and RCT. Expression of each marker was correlated with initial response, local control, and cancer-specific survival with preserved bladder. An exploratory multivariate analysis was also performed that included clinical and immunohistochemical variables. RESULTS: A high AI (> median = 1.6%) and a high Ki-67 index (> median = 8.8%), but not the p53- and bcl-2 expression, were significantly related to initial complete response (CR) and local control with preserved bladder after 5 years. When the AI and Ki-67 expression were considered simultaneously, the association with initial CR (p < 0. 001), local control (p = 0.0002), and cancer-specific survival with preserved bladder (p = 0.008) was highly significant. In an exploratory multivariate analysis (final model), only AI, Ki-67, and the combined AI/Ki-67 variable retained significance for local control with preserved bladder at 5 years. CONCLUSION: Patients with a high spontaneous AI and a high pretreatment Ki-67 index should be considered preferentially for treatment with RCT, whereas tumors with low proliferation and low levels of apoptosis are less likely to respond to RCT.