Incidence, Clinicopathological Risk Factors, Management and Outcomes of Nonmuscle Invasive Recurrence after Complete Response to Trimodality Therapy for Muscle Invasive Bladder Cancer.

Purpose: We describe the incidence, clinicopathological risk factors, management and outcomes of recurrent nonmuscle invasive bladder cancer after a complete response to trimodality therapy of muscle invasive bladder cancer.

Materials And Methods: We retrospectively reviewed the records of 342 patients with cT2-4aN0M0 muscle invasive bladder cancer and a complete response after trimodality therapy from 1986 to 2013. Using competing risks analyses we examined the association between baseline clinicopathological variables and nonmuscle invasive bladder cancer outcomes.

Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer.

Background: Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown.

Methods: In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.

Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience.

Background: Tri-modality therapy (TMT) is a recognized treatment strategy for selected patients with muscle-invasive bladder cancer (MIBC).

Objective: Report long-term outcomes of patients with MIBC treated by TMT.

Design, Setting, And Participants: Four hundred and seventy-five patients with cT2-T4a MIBC were enrolled on protocols or treated as per protocol at the Massachusetts General Hospital between 1986 and 2013.

Clinical Outcomes of Patients with Histologic Variants of Urothelial Cancer Treated with Trimodality Bladder-sparing Therapy.

Background: Trimodality bladder-sparing therapy (TMT) is an acceptable treatment for selected patients with muscle-invasive urothelial cancer. Outcomes of TMT in histologic variants remains largely unknown.

Objective: To compare outcomes of pure urothelial carcinoma (PUC) to variant urothelial carcinoma (VUC) after TMT.

Acute and late urinary toxicity following radiation in men with an intact prostate gland or after a radical prostatectomy: A secondary analysis of RTOG 94-08 and 96-01.

Introduction: To estimate the contribution of the prostate gland and prostatic urethral inflammation to urinary symptoms after radiation therapy for prostate cancer, we performed a secondary analysis of urinary toxicity after primary radiation to an intact prostate vs. postprostatectomy radiation to the prostatic fossa in protocols RTOG 94-08 and 96-01, respectively.

Materials And Methods: Patients randomized to the radiation-alone arms (without hormone therapy) of the 2 trials were evaluated, including 104 men receiving primary prostate radiation to 68.

Long-Term Outcomes Among Patients Who Achieve Complete or Near-Complete Responses After the Induction Phase of Bladder-Preserving Combined-Modality Therapy for Muscle-Invasive Bladder Cancer: A Pooled Analysis of NRG Oncology/RTOG 9906 and 0233.

Purpose: To investigate the differences in outcomes among patients with muscle-invasive bladder cancer on NRG Oncology Radiation Therapy Oncology Group protocols 9906 and 0233 who achieved complete response and near-complete response after induction chemoradiation and then completed bladder-preserving therapy with chemoradiation therapy (chemo-RT) to full dose (60-64 Gy).

Patients And Methods: A pooled analysis was performed on 119 eligible patients with muscle-invasive bladder cancer enrolled on NRG Oncology Radiation Therapy Oncology Group trials 9906 and 0233, who were classified as having a complete (T0) or near-complete (Ta or Tis) response after induction chemo-RT and completed consolidation with a total RT dose of at least 60 Gy. Bladder recurrence, salvage cystectomy rates, and disease-specific survival were estimated by the cumulative incidence method and bladder-intact and overall survivals by the Kaplan-Meier method.

Long-term outcomes of organ preservation in patients with small cell carcinoma of the bladder.

Background: Small cell carcinoma of the bladder is an uncommon but clinically aggressive disease. There is no standard surgical or medical management for the disease.

Methods: Between 1995 and 2009, 28 patients underwent transurethral resection (TUR) and/or cystectomy, chemotherapy, and/or radiation for small cell carcinoma of the bladder at our institution.

Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233.

Purpose: Multiple prospective Radiation Therapy Oncology Group (RTOG) protocols have evaluated bladder-preserving combined-modality therapy (CMT) for muscle-invasive bladder cancer (MIBC), reserving cystectomy for salvage treatment. We performed a pooled analysis of long-term outcomes in patients with MIBC enrolled across multiple studies.

Patients And Methods: Four hundred sixty-eight patients with MIBC were enrolled onto six RTOG bladder-preservation studies, including five phase II studies (RTOG 8802, 9506, 9706, 9906, and 0233) and one phase III study (RTOG 8903).

Nomograms predicting response to therapy and outcomes after bladder-preserving trimodality therapy for muscle-invasive bladder cancer.

Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy.

Trimodality therapy for bladder conservation in treatment of invasive bladder cancer.

During the past 25 years, prospective clinical trials have established that bladder preservation therapy for select patients with muscle-invasive bladder cancer is a safe and effective alternative to an immediate cystectomy. Cisplatin-based chemoradiation is the most well-studied and accepted component of trimodality therapy; however, other systemic agents have recently been shown effective in combination with radiation therapy, increasing the range of options to allow for better personalization of care. In this review, the most recent advances in the field of bladder-preserving trimodality therapy are presented, and future directions for improving the outcomes are outlined.

Immunohistochemistry as an adjunct in the differential diagnosis of radiation-induced atypia versus urothelial carcinoma in situ of the bladder: a study of 45 cases.

Muscle invasive urothelial carcinoma has been treated with cystectomy ± adjuvant therapy. Recently, a bladder-sparing protocol has been offered to selected patients closely followed with surveillance biopsies. In this setting, radiation-induced changes (RAD-Ch) may be very difficult to distinguish from carcinoma in situ, and failing to recognize them may lead to overtreatment.

Complications and long-term results of salvage cystectomy after failed bladder sparing therapy for muscle invasive bladder cancer.

Purpose: Radical cystectomy has been the standard treatment for muscle invasive bladder cancer. Combined modality therapy involving transurethral bladder tumor resection, external beam radiation and chemotherapy is an effective alternative to cystectomy in selected patients. Salvage cystectomy is reserved for those in whom combined modality therapy fails.

Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience.

Background: Whether organ-conserving treatment by combined-modality therapy (CMT) achieves comparable long-term survival to radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) is largely unknown.

Objective: Report long-term outcomes of patients with muscle-invasive BCa treated by CMT.

Design, Setting, And Participants: We conducted an analysis of successive prospective protocols at the Massachusetts General Hospital (MGH) treating 348 patients with cT2-4a disease between 1986 and 2006.

Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06.

Purpose: In selected patients with muscle-invasive bladder cancer, combined-modality therapy (transurethral resection bladder tumor [TURBT], radiation therapy, chemotherapy) with salvage cystectomy, if necessary, can achieve survival rates similar to radical cystectomy. We investigated late pelvic toxicity after chemoradiotherapy for patients treated on prospective protocols.

Patients And Methods: Between 1990 and 2002, 285 eligible patients enrolled on four prospective protocols (Radiation Therapy Oncology Group [RTOG] 8903, 9506, 9706, 9906) and 157 underwent combined-modality therapy, surviving >or= 2 years from start of treatment with their bladder intact.

The results of concurrent chemo-radiotherapy for recurrence after treatment with bacillus Calmette-Guérin for non-muscle-invasive bladder cancer: is immediate cystectomy always necessary?

Objectives: To report our original experience in patients in whom bacille Calmette-Guérin (BCG) therapy has failed for T1 bladder cancer with subsequent progression to T2 disease treated with chemo-radiotherapy, as the management of recurrent high-grade T1 bladder cancer after failed BCG therapy is challenging, and radical cystectomy is the standard treatment because there are no well established second-line bladder-preserving therapies.

Patients And Methods: From 1988 to 2002, 18 patients with T2 recurrence after failure of BCG therapy for T1 bladder cancer were treated with chemo-radiotherapy at the authors' institution. Patients received a visibly complete transurethral resection of the bladder tumour (TURBT) and concurrent chemo-radiotherapy with a mid-treatment evaluation after 40 Gy.

Phase I-II RTOG study (99-06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy.

Objectives: To evaluate the safety, tolerance, protocol completion rate, tumor response rate, and patient survival of chemoradiotherapy for patients with muscle-invasive operable bladder cancer.

Methods: After transurethral resection of the tumor in patients with Stage T2-T4a bladder cancer, twice-daily radiotherapy with paclitaxel and cisplatin chemotherapy induction (TCI) was administered. If repeat biopsy showed less than Stage T1 disease, consolidation with TCI was given.

Bladder preservation: optimizing radiotherapy and integrated treatment strategies.

While radical cystectomy (RC) remains the standard of care for muscle-invasive transitional cell carcinoma of the bladder, a series of single-institution and cooperative-group trials with a long-term follow-up have shown that combined modality therapy for bladder preservation can provide selected patients with an excellent chance for long-term survival with an intact, functioning bladder. Strategies for preserving the bladder have developed over the past 20 years, with continued refinements in radiation therapy, chemotherapy and patient selection. The hallmarks of modern bladder-preserving therapy include: (i) careful patient selection; (ii) combined therapy with maximum transurethral resection of bladder tumour, radiation and concurrent chemotherapy; (iii) cystoscopic assessment of the response to therapy with prompt salvage cystectomy for nonresponders; (iv) careful follow-up with cystoscopic surveillance and prompt cystectomy for invasive recurrence.

Bladder-sparing approaches to invasive disease.

Although immediate radical cystectomy remains the standard of care for invasive bladder cancer, a large body of international experience from single institutions and cooperative groups has accumulated, suggesting favorable results with bladder-sparing approaches in appropriately selected patients. Modern selective bladder preservation with trimodality therapy, consisting of transurethral resection of the bladder tumor, radiation, and chemotherapy, can achieve complete response rates of 60-80%, 5-year survival rates of 50-60%, and survival rates with an intact bladder of 40-45%. Although no randomized comparisons between cystectomy and trimodality therapy exist, long-term data confirm that the 10-year overall and disease-specific survival rates for patients in bladder-sparing protocols are comparable to outcomes reported in contemporary cystectomy series.

Expression of the epidermal growth factor receptor and Her-2 are predictors of favorable outcome and reduced complete response rates, respectively, in patients with muscle-invading bladder cancers treated by concurrent radiation and cisplatin-based chemotherapy: a report from the Radiation Therapy Oncology Group.

Purpose: Erb-1 (epidermal growth factor receptor, EGFR) and Erb-2 (Her-2) are two of the best characterized members in the EGFR pathway. In many tumor types, overexpression of these proteins is associated with enhanced malignant potential. Our objective in this study was to investigate the clinical relevance of EGFR and Her-2 expression in bladder cancer cases from four prospective Radiation Therapy Oncology Group (RTOG) bladder preservation trials using cisplatin-containing chemoradiation (RTOG 8802, 8903, 9506, and 9706).