Karl M. Schrott

Combined-Modality Treatment and Selective Organ Preservation in Invasive Bladder Cancer: Long-Term Results

PURPOSE To evaluate our long-term experience with combined modality treatment and selective bladder preservation and to identify factors that may predict treatment response, risk of relapse, and survival. PATIENTS AND METHODS Between 1982 and 2000, 415 patients with bladder cancer (high-risk T1, n = 89; T2 to T4, n = 326) were treated with radiotherapy (RT; n = 126) or radiochemotherapy (RCT; n = 289) after transurethral resection (TUR) of the tumor. Six weeks after RT/RCT, response was evaluated by restaging-TUR. In case of complete response (CR), patients were observed at regular intervals. In case of persistent or recurrent invasive tumor, salvage-cystectomy was recommended. Median follow-up was 60 months (range, 6 to 199 months). RESULTS CR was achieved in 72% of patients. Local control after CR without muscle-invasive relapse was maintained in 64% of patients at 10 years. Distant metastases were diagnosed in 98 patients with an actuarial rate of 35% at 10 years. Ten-year disease-specific survival was 42%, and more than 80% of survivors preserved their bladder. Early tumor stage and a complete TUR were the most important factors predicting CR and survival. RCT was more effective than RT alone in terms of CR and survival. Salvage cystectomy for local failure was associated with a 45% disease-specific survival rate at 10 years. Cystectomy because of a contracted bladder was restricted to 2% of patients. CONCLUSION TUR with RCT is a reasonable option for patients seeking an alternative to radical cystectomy. Ideal candidates are those with early-stage and unifocal tumors, in whom a complete TUR is accomplished.

Organ-sparing treatment of advanced bladder cancer: A 10-year experience

PURPOSE Radical cystectomy is considered as standard therapy for muscle-invasive bladder cancer. We present 10-year results of bladder-sparing treatment by conservative surgery and radiotherapy +/- chemotherapy. METHODS AND MATERIALS From 1982 through 1991, 245 consecutive patients, mean age 66 years, with invasive bladder cancer (T2-3 or poor prognostic T1, no distant metastases) entered a prospective protocol with the objective of bladder preservation. Treatment consisted of transurethral resection (complete, if possible) and definitive radiotherapy with 56 Gy maximum dose (50.4 Gy minimum target dose) in 28 fractions. Since 1985, 139 patients received a simultaneous chemotherapy on 5 days in the first and fifth treatment week with either 25 mg/m2 cisplatin daily (79 patients) or 65 mg/m2 carboplatin (60 patients). Cystectomy was performed as salvage treatment for residual or recurrent invasive disease. The median follow-up at the date of analysis (12-31-92) was 5.9 years. RESULTS The overall survival was 47% after 5 years and 26% after 10 years. The 5-year survival according to the initial T-category was 60% for T1 (44 patients), 64% for T2 (47 patients), 43% for T3 (127 patients), and 16% for T4 (23 patients). The most important single prognostic factor was the amount of residual tumor after TUR (5-year survival 80% after R0, 53% after R1, and 31% after R2 resection, p < 0.01). Chemotherapy increased the rate of complete remission, but had no impact on 5-year survival (52% vs. 50%). Fifty-three salvage cystectomies were performed, all without severe complications, and 192 patients (79%) maintained a normal functioning bladder. The bladder preservation rate in 5-year survivors was 83%. CONCLUSIONS Organ-sparing treatment of advanced bladder cancer by transurethral surgery and definitive radiotherapy or radiochemotherapy is feasible and effective. The survival in this series is as good as in any comparable cystectomy series. Eighty-three percent of long-term survivors maintained their functioning bladders.

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.

Radiotherapy with and without cisplatin in bladder cancer

From October 1985 to December 1988, 67 patients with invasive bladder carcinoma T1-4 N0-2 M0 were treated with irradiation (50.4 Gy in 28 fractions in 6 weeks) and simultaneous cisplatin (25 mg/m2 per day on 5 consecutive days in the first and fifth irradiation week). After transurethral resection and irradiation plus cisplatin, complete remissions were achieved in 8/11 T1-, 14/16 T2-, 27/36 T3- and 1/4 T4-tumors. The complete remission rate 6 weeks after treatment according to the extent of preceeding transurethral surgery (TUR) was: R0: 67% (8/12); R1: 83% (20/24); R2: 70% (21/30); Rx: 1/1. In patients with incomplete TUR (R1-2), the complete remission rate was 76% (41/54). This was superior to the results of a historical control (76% vs. 45%, p less than 0.01). The estimated 3-year survival according to T-stage was: T1: 73%, T2-3: 68%, T4: 25%. The overall 3-year survival was unchanged as compared to our historical control (66% each). Severe complications have not been observed. We conclude that cisplatin will likely increase the local control rate after incomplete transurethral surgery. An improvement of survival seems unlikely.

Organ preservation in patients with invasive bladder cancer: initial results of an intensified protocol of transurethral surgery and radiation therapy plus concurrent cisplatin and 5-fluorouracil.

PURPOSE To assess safety, tolerance, and disease control of transurethral resection of the bladder tumor (TURB) plus concurrent cisplatin, 5-fluorouracil (5-FU), and radiation therapy (RT) with selective organ preservation in patients with bladder cancer. PATIENTS AND METHODS Forty-five patients with muscle-invading or high-risk T1 (G3, associated carcinoma in situ, multifocality, >5 cm) bladder cancer were entered into a protocol of TURB followed by concurrent cisplatin (20 mg/m(2)/day, 20-min infusion) and 5-FU (600 mg/m(2)/day, 120-hour continuous infusion), administered on Day 1-5 and 29-33 of RT (single dose 1.8 Gy, total dose to the bladder 54-59.4 Gy). Response was evaluated by restaging TURB 6 weeks later. In case of invasive residual or recurrent tumor, salvage cystectomy was recommended. Median follow-up was 35 months (range: 8-80 months). RESULTS Thirty-nine patients (87%) had no detectable tumor at restaging TURB; 29 patients (64%) have been continuously free of tumor in their bladders. A superficial relapse occurred in 4 patients, a muscle-invasive relapse in 6 patients. Overall survival and survival with preserved bladder was 67% and 54%, respectively, at 5 years. Hematologic Grade 3/4 toxicity occurred in 10%/4%; Grade 3 diarrhea occurred in 9%. Thirty-four patients (76%) completed the protocol as scheduled or with only minor deviations. One patient required salvage cystectomy because of a shrinking bladder. CONCLUSION This protocol of concurrent cisplatin/5-FU and RT has been associated with acceptable toxicity. The complete response rate of 87% and the 5-year survival with intact bladder of 54% are encouraging and compare favorably with our historical control series using RT with carboplatin and cisplatin alone.

Preliminary results of treatment of invasive bladder carcinoma with radiotherapy and cisplatin

From October 1985 to February 1988, 41 patients with invasive bladder cancers were treated with transurethral resection (TUR) and radiotherapy with simultaneous cisplatin chemotherapy at the University Hospital in Erlangen. Radiotherapy was performed as primary treatment in case of macroscopic residual tumor after TUR (n = 22) or as adjuvant treatment in patients with macroscopically complete transurethral resection (n = 19). Age ranged from 44 to 77 years. Radiotherapy was given in daily fractions of 1.8 Gy. The pelvis was treated with a box up to 41.4 Gy and the bladder was boosted up to 50.4 Gy by a rotation technique. Cisplatin was administered in the first and fifth treatment week on five consecutive days with 25 mg cisplatin/m2 per day as short infusion. Pathohistologic response was examined by control cystoscopy with biopsies from the deep layers 6 weeks after completing radiochemotherapy. Maximum follow-up is 24 months after control cystoscopy. After TUR plus radiochemotherapy, histologically confirmed complete remission rates according to T-stage were: 7/8 T1-, 26/31 T2-3-, and 2/2 T4-tumors. In patients with macroscopic tumor prior to radiochemotherapy, histological and cytological complete remission was achieved in 2/3 T1-, 14/18 T2-3-, and 1/1 T4-cancers with an overall complete response rate of 77%. In complete responders, 3 isolated local recurrences (2 T1- and one T3-recurrence) and two local recurrences with distant metastases have occurred until now. Six patients had only partial response. Mild to moderate side effects occurred frequently, but overall treatment tolerance was good even in older patients. Complications did not occur. So far, 7 cystectomies have been performed, 6 were a result of persistent or recurrent tumor and one a result of a contracted bladder after multiple TURs. Thirty-four of forty-one patients (83%!) maintained their bladder and normal bladder function. In conclusion, moderate dose radiation therapy (50 Gy) in combination with simultaneous cisplatin chemotherapy is a well-tolerated treatment and highly effective for controlling local disease and preservation of bladder function in invasive bladder cancers.

Combined-modality treatment and organ preservation in bladder cancer: Do molecular markers predict outcome?

Purpose:In invasive bladder cancer, several groups have reported the value of organ preservation by a combined-treatment approach, including transurethral resection (TUR-BT) and radiochemotherapy (RCT). As more experience is acquired with this organ- sparing treatment, patient selection needs to be optimized. Clinical factors are limited in their potential to identify patients most likely to respond to RCT, thus, additional molecular markers for predicting treatment response of individual lesions are sorely needed.Patients and Methods:The apoptotic index (AI) and Ki-67 index were evaluated by immunohistochemistry on pretreatment biopsies of 134 patients treated for bladder cancer by TUR-BT and RCT. Expression of each marker as well as clinicopathologic factors were then correlated with initial response, local control and cancer-specific survival with preserved bladder in univariate and multivariate analysis.Results:The median AI for all patients was 1.5% (range 0.2–7.4%). The percentage of Ki-67-positive cells in the tumors ranged from 0.2% to 85% with a median of 14.2%. A significant correlation was found for AI and tumor differentiation (G1/2: AI = 1.3% vs. G3/4: AI = 1.6%; p = 0.01). A complete response at restaging TUR-BT was achieved in 76% of patients. Factors predictive of complete response included T-category (p < 0.0001), resection status (p = 0.02), lymphovascular invasion (p = 0.01), and Ki-67 index (p = 0.02). For local control, AI (p = 0.04) and Ki-67 index (p = 0.05) as well as T-category (p = 0.005), R-status (p = 0.05), and lymphatic vessel invasion (p = 0.05) reached statistical significance. Out of the molecular markers only high Ki-67 levels were associated to cause-specific survival with preserved bladder. On multivariate analysis, T-category was the strongest independent factor for initial response, local control and cancer-specific survival with preserved bladder.Conclusion:The indices of pretreatment apoptosis and Ki-67 predict a favorable outcome in bladder cancer patients treated with TUR-BT and RCT. Molecular markers may help to select patients for an organ-sparing approach.Hintergrund:Mehrere Arbeitsgruppen konnten zeigen, dass eine multimodale organerhaltende Behandlung des invasiven Blasenkarzinoms unter Einsatz der transurethralen Resektion (TUR-BT) und anschließender Radiochemotherapie (RCT) zu Therapieergebnissen führt, die denen der primären Zystektomie gleichwertig sind. Je mehr Erfahrungen mit dieser Therapiestrategie gewonnen werden, umso genauer sollte die Patientenauswahl erfolgen. Das Potential klinischer Faktoren, Patienten zu identifizieren, die von einer RCT profitieren, ist limitiert. Prädiktive molekulare Marker sind hier dringend notwendig.Patienten und Methodik:Der Apoptoseindex (AI) und der Ki-67-Index wurden an prätherapeutischen Biopsien von 134 Patienten, die mittels TUR-BT und RCT behandelt wurden, immunhistochemisch bestimmt. Die Expression beider Marker sowie klinische Faktoren wurden anschließend mit der initialen Ansprechrate, der lokalen Kontrolle und dem krankheitsspezifischen Überleben mit intakter Blase univariat und multivariat korreliert.Ergebnisse:Der Median des AI aller Patienten betrug 1,5% (Spanne: 0,2-7,4%). Der Prozentsatz Ki-67-positiver Tumorzellen reichte von 0,2% bis 85% bei einem Median von 14,2%. Eine signifikante Korrelation zeigte sich zwischen AI und Tumordifferenzierung (G1/2: AI = 1,3% vs. G3/4: AI 1,6%; p = 0,01). Ein komplettes Ansprechen wurde bei 76% der Patienten zum Zeitpunkt der „Restaging“-TUR-BT erreicht. Prädiktive Faktoren für das komplette Ansprechen waren die T-Kategorie (p < 0,0001), der Resektionsstatus (p = 0,02), die Lymphgefäßinvasion (p = 0,01) und der Ki-67-Index (p = 0,02). In Bezug auf die lokale Kontrolle erreichten der AI (p = 0,04) und der Ki-67-Index (p = 0,05) sowie die T-Kategorie (p = 0,005), der Resektionsstatus (p = 0,05) und die Lymphgefäßinvasion (p = 0,05) statistische Signifikanz. Von den molekularen Markern war nur der Ki-67-Index mit dem krankheitsspezifischen Überleben mit erhaltener Blase korreliert. Die T-Kategorie war der stärkste unabhängige prognostische Faktor für alle drei Endpunkte in der multivariaten Analyse.Schlussfolgerung:Die Indizes für die prätherapeutische Apoptose und Ki-67 prädizieren einen günstigen Verlauf nach TUR-BT und RCT. Molekulare Marker können bei der Selektion von Patienten für ein organerhaltendes Therapieverfahren hilfreich sein.

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 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.Hintergrund: Die gegenwärtige Behandlungsoptionen beim oberflächlichen T1-Blasenkarzinom mit hohem Rezidivrisiko (G3, assoziiertes Tis, Multifokalität, Größe > 5 cm, multiple Rezidive) umfassen die sofortige Zystektomie oder die transurethrale Resektion (TURB) mit adjuvanter intravesikaler Therapie zum Zweck des Organerhalts. Wir haben die Wirksamkeit einer adjuvanten Radio- oder Radiochemotherapie bezüglich lokaler Kontrolle, Blasenerhalt, Rezidivrate und Langzeitüberleben bei T1-Blasenkarzinom mit hohem Risikoprofil untersucht. Patienten und Methoden: Von Mai 1982 bis Mai 1999 wurden 74 Patienten mit Hochrisiko-T1-Blasenkarzinom nach TURB bestrahlt (n = 17) oder radiochemotherapiert (n = 57). Die Radiotherapie begann vier bis acht Wochen nach TURB; im Median wurden 54 Gy (Spanne: 45 bis 60 Gy) mit einer Einzeldosis von 1,8 bis 2,0 Gy auf die Blase verabreicht. Seit 1985 erfolgte eine simultane Chemotherapie in der ersten und fünften Radiotherapiewoche mit Cisplatin (25 mg/m2/Tag) bei 33 Patienten, 14 Patienten mit reduzierter Kreatininclearance (< 50 ml/min) erhielten Carboplatin (65 mg/m2/Tag). Seit 1993 wurde eine Kombination von Cisplatin (20 mg/m2/Tag) und 5-Fluorouracil (600 mg/m2/Tag) bei 10 Patienten eingesetzt. Die Salvage-Zystektomie wurde für Patienten mit refraktärem Karzinom oder invasivem Rezidiv empfohlen. Zum Auswertezeitpunkt war die mediane Nachbeobachtungszeit für die überlebenden Patienten 57 Monate (Spanne: drei bis 174 Monate). Ergebnisse: Eine komplette Remission bei der Restaging-TURB nach Radiotherapie/Radiochemotherapie wurde bei 62 Patienten (83,7%) erreicht, von denen 35 (47% bezogen auf die Gesamtzahl der 74 behandelten Patienten) im weiteren Verlauf tumorfrei blieben; elf Patienten (18%) erlitten ein oberflächliches Rezidiv, 16 Patienten (26%) zeigten eine Tumorprogression nach initialer kompletter Remission. Das Gesamtüberleben nach fünf Jahren betrug 72%, nach zehn Jahren 50%; 77% der nach fünf Jahren überlebenden Patienten konnten ihre Blase erhalten. Prognostisch ungünstige Faktoren bezüglich des krankheitsspezifischen Überlebens waren eine nicht radikale (R1/2) initiale TURB (p = 0,12) und eine Behandlung nach multiplen Rezidiven (p = 0,07). Die kombinierte Radiochemotherapie war effektiver als die alleinige Bestrahlung (p = 0,1). Schlussfolgerung: Die adjuvante Radiotherapie/Radiochemotherapie ist eine alternative Behandlungsoption bei oberflächlichen Hochrisikoblasenkarzinomen mit hoher Heilungsrate und Blasenerhalt. Der Stellenwert der Radiotherapie im Vergleich zu anderen Behandlungsmethoden sollte in randomisierten Studien überprüft werden.

Radiotherapy alone or radiochemotherapy with platin derivatives following transurethral resection of the bladder. Organ preservation and survival after treatment of bladder cancer.

PurposeMultivariate analysis of prognostic factors influencing survival and bladder preservation after radiochemotherapy for bladder cancer following transurethral resection of the bladder (TURB)Patients and MethodsAt the University Hospital of Erlangen 333 patients with bladder cancer were treated with either radiotherapy alone (RT, n=128) or platin based radiochemotherapy (RCT, n=205) after TURB between 5/1982 and 5/1996. Two-hundred and eighty-two curative patients, with either muscle invasive or T1-high risk cancer, were analyzed. Median age was 66 years, median follow-up is 7.5 years. Uni- and multivariate analysis was performed for age, grade, R-status after initial TURB, T-category and treatment modality relevant to the endpoints initial response, survival and bladder preservation.ResultsTreatment related mortality was below 1%. Complete remissions were achieved at 57%, 70%, and 85% after RT or RCT with carbo- or cisplatin. This difference was multivariately significant. Further significant prognostic factors were pT-category and R-status. For all patients survival was 59% and 43% after 5 and 10 years. 79% of survivors could keep their own bladder. Five-year survival rates after RT alone, RCT with carbo- or cisplatin were 47%, 57%, and 69%, respectively. This was univariately significant. The only multivariately significant factor for survival and bladder preservation was the R-status after initial TURB.ConclusionsTreatment of bladder cancer by TURB and RT/RCT is an alternative to primary cystectomy. The addition of chemotherapy leads to significantly more complete remissions and better survival. Initial TURB is recommended to be as radical as possible.ZusammenfassungZielMultivariate Analyse prognostischer Faktoren für Überleben und Blasenerhalt nach Radiochemotherapie des Harnblasenkarzinoms.Patienten und MethodeZwischen Mai 1982 und Mai 1996 wurden an der Strahlentherapeutischen Universitätsklinik Erlangen 333 Patienten wegen eines Harnblasenkarzinoms behandelt. Nach einer transurethralen Resekii on (TURB) erhielten sie entweder eine alleinige Radiotherapie (RT, n = 128) oder eine platinhaltige simultane Radiochemotherapie (RCT, n= 205). 282 kurative Patienten mit muskelinvasiven oder T1-high-risk-Tumoren wurden analysiert. Das mediane Erkankungsalter betrug 66 Jahre, die mediane Nachbeobachtung 7,5 Jahre. Mit den Einflußgrößen Alter, Differenzierungsgrad, R-Status, T-Kategorie und Behandlungsart (RT vs. RCT) wurden für die Endpunkte initiale Remission, Überleben und Blasenerhalt uni- und multivariate Analysen durchgeführt.ErgebnisseTherapieassoziiert starb ein Patient. Nach alleiniger RT, RCT mit Carbo- bzw. Cisplatin wurden komplette Remissionen von 57%, 70% und 85% erreicht. Dieser Unterschied war multivariat signifikant. Weitere signifikante Faktoren waren pT-Kategorie und R-Status. Für alle Patienten fand sich ein Überleben von 59% bzw. 43% nach fünf und zehn Jahren. 79% der Überlebenden weisen eine eigene funktionierende Blase auf. Univariat signifikant unterschieden sich die Überlebensraten nach RT. RCT mit Carbo- oder Cisplatin (47%, 57% und 69%). Der einzige multivariat signifikante prognostische Faktor war der R-Status nach initialer TURB.SchlußfolgerungenDie Strahlentherapie des Blasenkarzinoms nach TURB ist eine Alternative zur primären Zystektomie, da sie bei vergleichbaren Überlebensraten bei 79% der Patienten zum Organerhalt führt. Die der RT/RTC vorausgehende TURB muß so radikal wie möglich durchgeführt werden.

Combined-Modality Treatment and Organ Preservation in Bladder Cancer

Purpose:In invasive bladder cancer, several groups have reported the value of organ preservation by a combined-treatment approach, including transurethral resection (TUR-BT) and radiochemotherapy (RCT). As more experience is acquired with this organ- sparing treatment, patient selection needs to be optimized. Clinical factors are limited in their potential to identify patients most likely to respond to RCT, thus, additional molecular markers for predicting treatment response of individual lesions are sorely needed.Patients and Methods:The apoptotic index (AI) and Ki-67 index were evaluated by immunohistochemistry on pretreatment biopsies of 134 patients treated for bladder cancer by TUR-BT and RCT. Expression of each marker as well as clinicopathologic factors were then correlated with initial response, local control and cancer-specific survival with preserved bladder in univariate and multivariate analysis.Results:The median AI for all patients was 1.5% (range 0.2–7.4%). The percentage of Ki-67-positive cells in the tumors ranged from 0.2% to 85% with a median of 14.2%. A significant correlation was found for AI and tumor differentiation (G1/2: AI = 1.3% vs. G3/4: AI = 1.6%; p = 0.01). A complete response at restaging TUR-BT was achieved in 76% of patients. Factors predictive of complete response included T-category (p < 0.0001), resection status (p = 0.02), lymphovascular invasion (p = 0.01), and Ki-67 index (p = 0.02). For local control, AI (p = 0.04) and Ki-67 index (p = 0.05) as well as T-category (p = 0.005), R-status (p = 0.05), and lymphatic vessel invasion (p = 0.05) reached statistical significance. Out of the molecular markers only high Ki-67 levels were associated to cause-specific survival with preserved bladder. On multivariate analysis, T-category was the strongest independent factor for initial response, local control and cancer-specific survival with preserved bladder.Conclusion:The indices of pretreatment apoptosis and Ki-67 predict a favorable outcome in bladder cancer patients treated with TUR-BT and RCT. Molecular markers may help to select patients for an organ-sparing approach.Hintergrund:Mehrere Arbeitsgruppen konnten zeigen, dass eine multimodale organerhaltende Behandlung des invasiven Blasenkarzinoms unter Einsatz der transurethralen Resektion (TUR-BT) und anschließender Radiochemotherapie (RCT) zu Therapieergebnissen führt, die denen der primären Zystektomie gleichwertig sind. Je mehr Erfahrungen mit dieser Therapiestrategie gewonnen werden, umso genauer sollte die Patientenauswahl erfolgen. Das Potential klinischer Faktoren, Patienten zu identifizieren, die von einer RCT profitieren, ist limitiert. Prädiktive molekulare Marker sind hier dringend notwendig.Patienten und Methodik:Der Apoptoseindex (AI) und der Ki-67-Index wurden an prätherapeutischen Biopsien von 134 Patienten, die mittels TUR-BT und RCT behandelt wurden, immunhistochemisch bestimmt. Die Expression beider Marker sowie klinische Faktoren wurden anschließend mit der initialen Ansprechrate, der lokalen Kontrolle und dem krankheitsspezifischen Überleben mit intakter Blase univariat und multivariat korreliert.Ergebnisse:Der Median des AI aller Patienten betrug 1,5% (Spanne: 0,2-7,4%). Der Prozentsatz Ki-67-positiver Tumorzellen reichte von 0,2% bis 85% bei einem Median von 14,2%. Eine signifikante Korrelation zeigte sich zwischen AI und Tumordifferenzierung (G1/2: AI = 1,3% vs. G3/4: AI 1,6%; p = 0,01). Ein komplettes Ansprechen wurde bei 76% der Patienten zum Zeitpunkt der „Restaging“-TUR-BT erreicht. Prädiktive Faktoren für das komplette Ansprechen waren die T-Kategorie (p < 0,0001), der Resektionsstatus (p = 0,02), die Lymphgefäßinvasion (p = 0,01) und der Ki-67-Index (p = 0,02). In Bezug auf die lokale Kontrolle erreichten der AI (p = 0,04) und der Ki-67-Index (p = 0,05) sowie die T-Kategorie (p = 0,005), der Resektionsstatus (p = 0,05) und die Lymphgefäßinvasion (p = 0,05) statistische Signifikanz. Von den molekularen Markern war nur der Ki-67-Index mit dem krankheitsspezifischen Überleben mit erhaltener Blase korreliert. Die T-Kategorie war der stärkste unabhängige prognostische Faktor für alle drei Endpunkte in der multivariaten Analyse.Schlussfolgerung:Die Indizes für die prätherapeutische Apoptose und Ki-67 prädizieren einen günstigen Verlauf nach TUR-BT und RCT. Molekulare Marker können bei der Selektion von Patienten für ein organerhaltendes Therapieverfahren hilfreich sein.