Prognostic factors of primary transitional cell carcinoma of the upper urinary tract

OBJECTIVES: We presented and analyzed our results in order to determine the relationship between patient survival and tumor grade and/or stage. In addition, a retrospective tumor DNA ploidy study was done to evaluate its possible role in predicting future tumor recurrence in the bladder. METHODS: A total of 112 patients with upper urinary tract transitional cell carcinomas (TCCs) were recorded at our hospital. Of these, 68 patients without concurrent bladder tumors (ages ranged from 36 to 80, mean 62.4 years; male:female = 1:1.2) were treated by nephroureterectomy and bladder cuff resection. They were followed up for 14-79 months (average 38.2 months). Eight (36.4%) of the 22 patients who had stage C or D tumors had received adjuvant systemic methotrexate, vinblastine, epirubicin, cisplatin chemotherapy after surgery. DNA flow cytometry using paraffin-blocked tumor specimens was performed on the tumors of 52 patients. RESULTS: Their pathologic stages and grades were 11 at stage 0, 15 at stage A, 20 at stage B, 14 at stage C, 8 at stage D; 9 of grade I, 41 of grade II, and 18 of grade III. Postoperatively, 13 patients (19.1%) subsequently developed bladder tumors with a latent period ranging from 2 to 37 months (average 14.9 months). The difference of the tumor DNA ploidy distribution pattern among tumors of high versus low stages and/or grades is not statistically significant (p > 0.05). Overall, the 5-year survival rates for patients with low- and high-stage tumors were 100 and 66.7%, respectively; for patients with grade I-II and III tumors they were 93.6 and 28.3%, respectively. CONCLUSIONS: Patient survival was mainly related to both tumor stages (p = 0.0037) and grades (p = 0.0001), rather than to tumor DNA ploidy. For patients with grade II upper urinary tract tumors, tumor DNA ploidy seems to provide no additional predictive value on subsequent tumor recurrence in the bladder.     

Utility of the Bard BTA test in detecting upper urinary tract transitional cell carcinoma

OBJECTIVES: The Bard BTA test has been shown in early studies to be useful in diagnosing transitional cell carcinoma (TCC) of the bladder. However, the utility of this test has not been evaluated for TCC of the upper urinary tract. We therefore evaluated the clinical utility of the BTA test for upper urinary TCC. METHODS: We tested 71 specimens from the ureter and/or renal pelvis in 22 patients with a history or clinical suspicion for TCC and 9 patients with benign disorders. RESULTS: When compared to cytologic diagnoses, BTA had a sensitivity of 65%, a specificity of 40% (when correlated with clinical history), a false-positive rate of 33%, and a false-negative rate of 62%. The test had a positive predictive value of 83% and a negative predictive value of 32%. CONCLUSIONS: The BTA does not have any clinical value in detecting upper urinary tract TCC.     

Computed tomography for detection and staging of transitional cell carcinoma of the upper urinary tract

A total of 91 patients were treated for upper tract urothelial tumors between 1981 and 1991. Preoperative computed tomography (CT) scans and nephroureterectomy for treatment of transitional cell carcinoma were performed in 26 patients. At pathological examination, 28 tumors were diagnosed of which 19 were in the renal pelvis and 7 were in the ureter. Intravenous pyelogram, retrograde and antegrade pyelogram detected 26 of 28 tumors (93%). CT detected 24 of 28 tumors (86%). However, CT is still the best current method for staging of upper urinary tract urothelial tumors, although staging was correct in only 5 of 9 T3 and T4 tumors.     

Recurrent urothelial tumors following surgery for transitional cell carcinoma of the upper urinary tract

A retrospective analysis of 74 cases of transitional cell carcinoma of the renal pelvis and ureter treated at this institution over the past 30 years is presented. When nephrectomy alone or incomplete nephroureterectomy was performed, subsequent transitional cell carcinoma developed in 30% of the ureteral stumps. Subsequent bladder carcinoma occurred in 25% of the patients with primary upper urinary tract carcinoma. The type of initial surgery performed did not appear to influence this incidence of subsequent bladder tumors. Contralateral upper urinary tract carcinoma developed in only one patient. When nephroureterectomy is performed for carcinoma of the renal pelvis and ureter, a cuff of bladder that includes the ureteral orifice should be removed to obviate recurrent disease in the ureteral stump. Since single-incision nephroureterectomy did not include the intramural ureter in 50% of the cases in which it was performed, a second incision may be required for adequate exposure.     

Urinary nuclear matrix protein as a marker for transitional cell carcinoma of the urinary tract

PURPOSE: The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as an indicator for transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS: Three groups of subjects participated in this trial of NMP22: 1-175 with transitional cell carcinoma, 2-117 with benign urinary tract conditions and 3-375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22. RESULTS: In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels. CONCLUSIONS: NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.     

Doxorubicin hydrochloride, cyclophosphamide, and 5-fluorouracil combination in advanced prostate and transitional cell carcinoma

Hubbard cockerels, 1 day of age (n = 91), were divided into 3 handling groups: (1) chicks from the 5-Day group were removed from the brooder and isolated at 22 degrees C for 3 min on each of the first 5 days; (2) chicks from the 15-Day group received this treatment for 15 days; and (3) Control chicks were not handled. Within each group half were fed broiler starter for 5 weeks, and half were fed layer starter which produces slower growth. On Days 28, 35, 42, and 49 the average weight of 5-Day birds was significantly higher than that of Controls; 15-Day birds weighed slightly less than birds in the 5-Day group. The weight advantage of the 5-Day birds occurred with both starter rations, at all weighing periods, and did not appear to reflect increased food consumption. Similarities between these findings and results obtained with rodents were noted.     

Phase II trials of 5-fluorouracil and leucovorin in patients with metastatic gastric or pancreatic carcinoma

BACKGROUND: Previous trials in patients with colorectal carcinoma have indicated that enhancement of 5-fluorouracil (5-FU) by leucovorin (LV) can result in an improved response rate and increased survival. METHODS: Phase II trials were performed with patients who had either gastric or papcreatic adenocarcinoma with inetastases. Forty-one gastric carcinoma patients and 31 pancreatic carcinoma patients with measurable disease were treated with 5-FU, 425 mg/m2 intraveneosly (i.v.) on Days 1-5 plus LV, 20 mg/m2 i.v., on Days 1-5, reported at 4 and 8 weeks, and then every 5 weeks thereafter. RESULTS: The patients with metastatic gastric carcinoma had a median survival of 4.8 months. There was a 22% objective response rate, including a 4.9% complete response rate and a 17.1% partial response rate. Among the 31 patients with pancreatic carcinoma, there was a median survival of 5.7 months. No patients in this group showed a response. CONCLUSIONS: The response rate for patients with metastatic gastric adenocarcinoma was modest and this regimen may provide temporary palliation for some patients. However, 5-FU and LV treatment is ineffective against metastatic pancreatic carcinoma.     

A phase II study of DaunoXome in advanced urothelial transitional cell carcinoma

Liposomal encapsulation of anthracyclines is claimed to reduce toxicity and to improve pharmacokinetics. Therefore, 15 patients with locally advanced or metastatic transitional cell cancer (TCC) of the urinary tract were entered into a phase II study assessing the response rate (WHO criteria) and toxicity of DaunoXome 100 mg/m2 given as a 1 h infusion every third week. During treatment, 6 patients remained stable and 8 had progressive disease. 1 patient died of pulmonary embolism after the first cycle and was not evaluable for response. No patient developed grade 4 myelotoxicity. Grade 3 leucopenia was seen in 5 patients and grade 1 thrombocytopenia in 1 patient, with no treatment-related changes of biochemical liver and kidney function tests. 4 patients complained of angina pectoris-like chest pain during the initial phase of the first or second infusion. The event was associated with a decrease in systolic blood pressure by 20-30 mm in 1 patient leading to permanent treatment discontinuation. In the other 3 and all subsequent patients, intramuscular application of 100 mg hydrocortisone 1 h prior to DaunoXome infusion prevented similar hypotensive reactions. In this study, intravenous (i.v.) DaunoXome 100 mg/m2 every third week showed no anticancer activity in advanced TCC.     

Phase II trial of 5-fluorouracil, interferon-alpha and continuous infusion interleukin-2 for patients with metastatic renal cell carcinoma

BACKGROUND: This study was designed to evaluate the efficacy and toxicity of the combination of 5-fluorouracil, interferon-alpha, and interleukin-2 for patients with metastatic renal cell carcinoma. METHODS: Previously untreated patients with a Zubrod performance status of < or =2; adequate cardiac, pulmonary, and renal function; and absence of brain metastases were eligible. One course of therapy was 28 days. 5-fluorouracil was administered at a dose of 600 mg/m2/day as a continuous infusions on Days 1-5. Interleukin-2 also was administered as a continuous infusion on Days 1-5 at a dose of 2 million Roche U/m2/day. Interferon-alpha was given as a daily subcutaneous injection of 4 million U/m2/day. RESULTS: Fifty-five patients were enrolled in the trial and 52 were evaluable for response. All patients experienced fever and flu-like symptoms. Grade 3 or 4 nonhematologic toxic effects included hypertension (48%), dermatitis (12%), stomatitis (11%), and altered mental status (9%). There was one toxic death. Four complete responses and 12 partial responses were observed for a total response rate of 31% (95% confidence interval, 18-46%). The survival of responding patients was significantly better than that of nonresponding patients. The improvement in survival was even more significant when comparing patients with at least stable disease with those who progressed through treatment. CONCLUSIONS: The three-drug combination described in this study demonstrates activity. However, it appears to be more toxic than other regimens with similar response rates and cannot be recommended for standard practice. Changing the interleukin-2 route to subcutaneous administration may permit more continuous administration with less toxic effects.     

Phase II study of divided-dose vinblastine in non-small cell bronchogenic carcinoma

A role for vinblastine (VBL) in lung cancer has never been clearly defined. Because of recent pharmacokinetic data suggesting a biweekly schedule for VBL and recent antitumor activity shown for vindesine, a phase II trial of divided-dose VBL was initiated. Among 22 evaluable patients, a 27% major response rate was seen, with a median duration of 5.5 months (range 3.5-12+). The major toxic effect was myelosuppression but was easily manageable and tolerated. These results suggest schedule dependency for VBL and open the question of its efficacy in lung cancer.     

Phase II clinical and pharmacological study of pirarubicin in combination with 5-fluorouracil and cyclophosphamide in metastatic breast cancer

Doxorubicin containing combination chemotherapy regimens are widely used for treatment of breast and other cancers. However, these regimens are associated with significant toxicities including myocardial dysfunction and alopecia. Analogues of doxorubicin are being developed to reduce these side effects. We conducted a Phase II trial of an anthracycline analogue, pirarubicin, administered in combination with 5-fluorouracil and cyclophosphamide every 3 weeks, as front-line chemotherapy in women with metastatic breast cancer. Patients who had received prior anthracycline therapy were excluded. The chemotherapy doses were as follows: 5-fluorouracil (500 mg/m2 on days 1 and 8), pirarubicin (50 mg/m2 on day 1), and cyclophosphamide (500 mg/m2 on day 1). Among 40 evaluable patients treated on this protocol, a major response (partial or complete remission) was observed in 26 patients (response rate, 62%; 95% confidence interval, 46-77). The median response duration was 8 months, and median survival was 16 months. Grade III/IV myelosuppression occurred in 81% of the courses. The median cumulative pirarubicin dose was 410 (range, 90-870) mg/m2. A significant decrease in left ventricular ejection fraction occurred in 12 patients (at a median cumulative pirarubicin dose of 460 mg/m2) and led to congestive heart failure in 4 of these patients (cumulative pirarubicin doses of 500, 520, 590, and 730 mg/m2, respectively). Eleven patients underwent endomyocardial biopsy, either because they experienced a drop in left ventricular ejection fraction or because they had received a cumulative pirarubicin dose of 600 mg/m2 and were still responding to the treatment. Of these, only one biopsy was found to be more than grade 1.0 (in an individual who had received a cumulative dose of 705 mg/m2). Severe alopecia occurred in two-thirds of the patients. Pharmacokinetic studies revealed a triphasic elimination of pirarubicin with alpha, beta and gamma half-lives of 0.12, 1.44, and 33.9 h, respectively. Total clearance of drug was 4.2 liters.1 h/kg while the cumulative 24-h urinary excretion was less than 10% of the administered dose. The activity of the combination appears to be similar to doxorubicin-containing regimens, while the incidence of alopecia appears to be lower than the historical experience with doxorubicin. However, cardiotoxicity remains a significant problem.     

Immunohistochemical studies of proliferating cell nuclear antigen and cathepsin D in transitional cell carcinoma of the urinary bladder

Immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and cathepsin D was performed on 60 transitional cell carcinoma (TCC) specimens from 60 patients with bladder cancer. The percentage of PCNA-positive cells (PCNA-labelling index) was determined by counting 500 or 1,000 cells, and cathepsin D expression was graded according to the extent of immunoreactivity to anti-cathepsin D antibody. The PCNA-labelling index was significantly higher in high-grade and high-stage tumors compared to that in low-grade and low-stage tumors. Cathepsin D was highly positive in grade-1 tumors. In contrast, 82% of grade-3 tumors and 76% of advanced tumors showed negative or low reactivity to anti-cathepsin D. Groups of high PCNA-labelling index and negative cathepsin D had significantly poorer prognoses compared to those of the low PCNA group and cathepsin D highly positive group, respectively, in univariate analyses. However, neither of these two factors were independent prognostic factors in multivariate analyses. These results suggest that the PCNA-labelling index and cathepsin D expression may indicate the malignant potential of TCC and may be able to provide additional information for predicting survival when stratifying for grade of bladder cancer.     

Myxoid and sclerosing sarcomatoid transitional cell carcinoma of the urinary bladder: a clinicopathologic and immunohistochemical study of 25 cases

We report 25 sarcomatoid carcinomas of the urinary bladder with a prominent myxoid and/or sclerotic appearance. The average age of the patients was 72 years (range, 50-92 yr); 14 were men, and 11 were women. The cystoscopic appearance varied from a large polypoid mass to an intramural mass with bladder wall thickening, often with necrosis and ulceration. The tumors ranged from 3 to 10 cm and were typically rubbery or gelatinous with a brown, pink, or gray color. Microscopy revealed tapering spindle cells with a variable admixture of cohesive non-spindled cells. Twenty-two cases had an invasive overtly epithelial carcinomatous component, and in situ transitional carcinoma was present in 12 cases. All of the cases had areas with myxoid change, ranging from extensive to focal, separating the spindle cells. Fourteen cases had areas of sclerosis. In all the cases, the spindle cells were atypical, at least focally, with hyperchromatic pleomorphic nuclei, prominent nucleoli, and coarse chromatin. Mitotic activity was prominent in the majority of cases, and abnormal mitotic figures were frequent. In eight cases, the myxoid histologic pattern was very reminiscent of an inflammatory pseudotumor, a diagnosis frequently entertained and erroneously made in one case; many of the spindle cells in three of these cases were mildly atypical, with minimal mitotic activity. The spindle cells were immunoreactive for cytokeratin (12 of 19), vimentin (16 of 17), carcinoembryonic antigen (3 of 15) and muscle-specific actin (4 of 16), and nonreactive for epithelial membrane antigen, desmin, S-100, KP1, CD34, and Leu-M1. The epithelioid carcinomatous areas were highlighted by the cytokeratin immunostain. These features and the conventional light microscopic features indicative of a diagnosis of carcinoma distinguish this tumor from reactive of neoplastic mesenchymal lesions.     

Killing effects of 5-fluorouracil on human biliary tract cancer cell lines

Previous studies have established that a partially quaternized derivative of chitosan, N-trimethyl chitosan chloride (TMC), can be used as an absorption enhancer for large hydrophilic compounds across mucosal surfaces. This study evaluates and compares the effects of the degree of quaternization of TMC, in a neutral environment, on the permeability of intestinal epithelial cells in vitro, where normal chitosan salts are ineffective as absorption enhancers. The effects of TMC-H [61.2% quaternized, (0.05-1.5% w/v)], TMC-L [12.3% quaternized, (0.5-1.5% w/v)], and chitosan hydrochloride [0.5-1.5% w/v] on the transepithelial electrical resistance (TEER) and permeability, for the hydrophilic model compound [14C]mannitol, of intestinal epithelial Caco-2 cell monolayers, were investigated at pH values of 6.20 and 7.40. The viability of the monolayers was checked with the trypan blue exclusion technique. At a pH of 6.20, all the polymers caused a pronounced reduction (37-67% at 0.5% w/v concentrations) in the TEER of Caco-2 cells. On the contrary, at a pH of 7.40, only TMC-H was able to decrease the TEER values, even in a concentration as low as 0.05% w/v (35% reduction). Comparable results were obtained with the permeation of [14C]mannitol. Large increases in the transport rate (18-23-fold at 0.5% w/v concentrations) were found at pH 6.20, whereas only TMC-H was able to increase the permeation of [14C]mannitol at pH 7.40 (31-48-fold at 0.05-1.5% w/v concentrations of TMC-H). For all the polymers studied, no deleterious effects to the cells could be demonstrated with the trypan blue exclusion technique. It is concluded that highly quaternized TMC is a potent absorption enhancer and the potential use of this polymer, especially in neutral and basic environments where normal chitosan salts are not effective, is expected to be an important contribution to the development of effective delivery systems for hydrophilic compounds such as peptide drugs.     

The correlation of membranous glycoprotein-gp-170, cytoplasmic glutathione and glucose-6-phosphate dehydrogenase levels with multidrug resistance in transitional cell carcinoma cell lines of the urinary tract

The expression of membranous glycoprotein gp-170, cytoplasmic glutathione (GSH) and energy-related glucose-6-phosphate dehydrogenase (G-6-PD) in cultured normal urothelial cells and transitional cell carcinoma (TCC) cell lines was analyzed by flow cytometric and enzymatic methods. The chemosensitivity of these tumor cells to four major types of anticancer drugs, including cisplatin, thiotepa, methotrexate, 5-fluorouracil, adriamycin and vinblastine, was correlated with biological activities in TCC cell lines. The TCC cell lines displayed a general sensitivity to anticancer drugs with a low incidence of highly resistant cell lines (23%). The expression of multidrug resistance was not related to cellular differentiation or invasiveness of cancer cells. Only 24% of TCC cell lines had an elevated expression of gp-170, but their expression was not related to drug resistance. Increased cytoplasmic GSH and G-6-PD was observed in over 90 per cent of TCC cell lines, but no correlation with drug resistance and cellular differentiation was observed. The biological activities of GSH and G-6-PD were not related to the drug resistance of TCC. The low expression rate of gp-170 in TCC cells indicates that other mechanisms should be involved in the development of MDR in TCC cells.     

"Non-condensed" and "condensed" chromain in transitional cell carcinoma of the human urinary bladder

The area and content of "non-condensed" and "condensed" chromatin in smeared Feulgen-stained malignant urothelial cells were determined by means of scanning-cytophotometry. The results were compared with those from similar measurements of benign human transitional epithelial cells. There was no difference between the relative area and content of "non-condensed" and "condensed" chromatin in cancer nuclei and normal urothelial nuclei as far as nuclei of the same size and ploidy class were considered. Within the same ploidy class the relative area and content of "non-condensed" chromatin increased with increasing nuclear size. As increased nuclear size within the same ploidy class is typical for most cancer cells, cancer specimens therefore contained relatively more "non-condensed" chromatin than normal urothelium. Analogously the relative values of "condensed" chromatin decreased in cancer specimens. Only in high-polyploid cancer cells, which occurred more frequently in undifferentiated tumours, a slight decrease of the relative area and content of "non-condensed" chromatin was observed as compared with well differentiated diploid tumour cells. It was in polyploid tumours that the absolute area and content of "condensed" chromatin was increased as compared with diploid normal urothelium. This means that the changes in "non-condensed" and "condensed" chromatin were primarily dependent on nuclear size and total chromatin content and were not found to be a characteristic of cancer nuclei as compared with control nuclei of the same size and ploidy. These findings differ from the results of biochemical analyses of heterochromatin both in cells during carcinogenesis and also in cancer cells, but are in agreement with qualitative and quantitative morphological studies of smeared cancer nuclei.     

Accelerated hyperfractionated radiation therapy and concurrent 5-fluorouracil/cisplatin chemotherapy for locoregional squamous cell carcinoma of the thoracic esophagus: a phase II study

PURPOSE: To improve the poor prognosis of patients with locoregional esophageal squamous cell cancer, we used concurrent accelerated hyperfractionated radiation therapy (ACC HFX RT) and chemotherapy (CHT). MATERIAL AND METHODS: Between January 1988 and June 1993, 28 patients were treated with ACC HFX RT with 1.5 Gy twice daily, to a total dose of 54 Gy concurrently with 5-fluorouracil (5-FU) (300 mg/m2, days 1-5) and cisplatin (CDDP) (10 mg/m2, days 1-5), both given during weeks 1 and 4 of the ACC HFX RT course. Following the ACC HFX RT/CHT, two additional courses of 5-FU (500 mg/m2, days 1-5) and CDDP (20 mg/m2, days 1-5) were both given during weeks 7 and 10. The median age and Eastern Cooperative Oncology Group performance status were 62 and 1, respectively. The American Joint Committee on Cancer (AJCC) stage was I in 12 patients, II in 10, and III in 6. RESULTS: The median survival time was 26 months, and the 5-year survival rate was 29%. The rates at 5 years for freedom from relapse, locoregional recurrence, and distant metastasis were 29%, 61%, and 45%, respectively. Univariate analysis revealed that performance status, stage, weight loss, tumor length, and tumor location influenced survival, while age and sex did not. The most frequent acute high-grade (3 or 4) toxicities were esophagitis and leukopenia, seen in 50% and 39% of patients, respectively. Late high-grade toxicity was infrequent. There were no treatment-related deaths. CONCLUSION: The results of this study compare favorably with those of previous studies, albeit of relatively high incidence of acute high-grade toxicity. Further studies are warranted to compare its efficacy with other approaches.     

Synchronous multifocal development of invasive transitional cell carcinoma of the urinary tract in a patient with renal failure receiving long-term hemodialysis: a case report

We report a case of transitional cell carcinoma in a patient with chronic renal failure receiving hemodialysis for 22 years. A 55-year-old man was admitted to our hospital. Under diagnosis of invasive bladder cancer and left renal pelvic tumor, removal of the whole urinary tract, e.g., bilateral nephroureterectomy and total cystourethrectomy was performed. Transitional cell carcinoma was found in bilateral renal pelvis, left ureter, bladder and prostate in the resected specimen. Thirteen months after the operation, multiple lung metastases and pathologic bone fracture of the 4th lumber vertebra were found. Chemotherapy (3 courses of modified CISCA, consisting of cisplatin, adriamycin and cyclophosphamide) was performed, but the died of systemic metastases of cancer and bleeding due to perforation of multiple gastric ulcers.     

Quantitative studies of the kinetics of 5-aminolaevulinic acid-induced fluorescence in bladder transitional cell carcinoma

Photodynamic therapy is a potential treatment for superficial bladder cancer that utilizes photosensitizer drugs, which are activated by light to cause tissue destruction. However, first-generation photosensitizers cause prolonged phototoxicity, have poor tumour specificity and can accumulate within detrusor muscle, resulting in permanent loss of bladder capacity following treatment. A newer drug, called 5-aminolaevulinic acid (ALA), generates a sensitizer called protoporphyrin IX (PpIX) in situ and has been shown, qualitatively, to be more tumour specific. The fluorescence kinetics of ALA-induced PpIX was investigated in patient biopsies of bladder tumour, normal urothelium and detrusor muscle, both in vitro after incubation of specimens in ALA-rich culture medium for various times and in vivo after instillation of intravesical ALA before endoscopic resection. The fluorescence in tumour tissue was twice that of normal urothelium in vitro and up to tenfold in vivo. There was little ALA-induced fluorescence in detrusor muscle, both in vitro and in vivo. Most importantly, no patients experienced phototoxicity or other adverse events following intravesical instillation of ALA.