An in-depth overview of the normal-tissue radiation tolerance of the urinary bladder is presented. The most informative studies consider whole-organ irradiation. The data on partial-organ/nonuniform irradiation are suspect because the bladder motion is not accounted for, and many studies lack long enough follow-up data. Future studies are needed.

/pdf/radiation-dose-volume-effects-of-the-urinary-bladder-1p2564g7ar.pdf

Radiation dose-volume effects of the urinary bladder.

Importance Optimizing radiation therapy techniques for localized prostate cancer can affect patient outcomes. Dose escalation improves biochemical control, but no prior trials were powered to detect overall survival (OS) differences. Objective To determine whether radiation dose escalation to 79.2 Gy compared with 70.2 Gy would improve OS and other outcomes in prostate cancer. Design, Setting, and Participants The NRG Oncology/RTOG 0126 randomized clinical trial randomized 1532 patients from 104 North American Radiation Therapy Oncology Group institutions March 2002 through August 2008. Men with stage cT1b to T2b, Gleason score 2 to 6, and prostate-specific antigen (PSA) level of 10 or greater and less than 20 or Gleason score of 7 and PSA less than 15 received 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy to 79.2 Gy in 44 fractions or 70.2 Gy in 39 fractions. Main Outcomes and Measures Time to OS measured from randomization to death due to any cause. American Society for Therapeutic Radiology and Oncology (ASTRO)/Phoenix definitions were used for biochemical failure. Acute (≤90 days of treatment start) and late radiation therapy toxic effects (>90 days) were graded using the National Cancer Institute Common Toxicity Criteria, version 2.0, and the RTOG/European Organisation for the Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme, respectively. Results With a median follow-up of 8.4 (range, 0.02-13.0) years in 1499 patients (median [range] age, 71 [33-87] years; 70% had PSA P  = .98). The 8-year cumulative rates of distant metastases were 4% for the 79.2-Gy arm and 6% for the 70.2-Gy arm (HR, 0.65; 95% CI, 0.42-1.01; P  = .05). The ASTRO and Phoenix biochemical failure rates at 5 and 8 years were 31% and 20% with 79.2 Gy and 47% and 35% with 70.2 Gy, respectively (both P P  = .006 [HR, 1.39; 95% CI, 1.10-1.77] and P  = .003 [HR, 1.59; 95% CI, 1.17-2.16], respectively). Conclusions and Relevance Despite improvements in biochemical failure and distant metastases, dose escalation did not improve OS. High doses caused more late toxic effects but lower rates of salvage therapy. Trial Registration clinicaltrials.gov Identifier:NCT00033631

/pdf/effect-of-standard-vs-dose-escalated-radiation-therapy-for-49fftjf3h4.pdf

Effect of Standard vs Dose-Escalated Radiation Therapy for Patients With Intermediate-Risk Prostate Cancer: The NRG Oncology RTOG 0126 Randomized Clinical Trial.

PURPOSETo determine the relationship between acute gastrointestinal (GI) toxicity during the combined modality segment and the volume of small bowel in the pelvic radiation field in patients who receive either preoperative or postoperative therapy for rectal cancer.PATIENTS AND METHODSThe patient population was derived from four consecutive phase I dose-escalation trials. Combined modality therapy included fluorouracil (5-FU), leucovorin ([LV] bolus daily x 5, days 1 and 29), and pelvic radiation.RESULTSTwenty patients who received postoperative therapy had a larger volume of small bowel in the pelvic radiation field as compared with 60 who received preoperative therapy (462 +/- 129 v 212 +/- 44 cm3, P = .002). The most significant relationship between acute GI toxicity and volume of small bowel was seen in 12 patients who were treated on the preoperative sequential low-dose LV trial, all of whom received the maximum-tolerated dose (MTD) of 5-FU. The volume of small bowel in patients who experienced grade...

Relationship of acute gastrointestinal toxicity and the volume of irradiated small bowel in patients receiving combined modality therapy for rectal cancer

Muscle-invasive bladder cancer is an aggressive disease associated with high morbidity and mortality. Radical cystectomy is the mainstay of treatment and has evolved since the first reported cystectomy in 1887 to include pelvic lymph node dissection and the creation of increasingly sophisticated urinary diversions, such as neobladders and pouches, which enable patients to maintain continence. Pioneering work in the 1970s established the therapeutic activity of cisplatin in patients with bladder cancer and resulted in the introduction of cisplatin-based neoadjuvant chemotherapy, which led to the first improvement in survival outcomes in decades. Other notable advances include the development of bladder-sparing protocols, which combine surgery, chemotherapy, and radiotherapy. Molecular profiling of bladder cancer has helped to enhance our understanding of tumour biology and identify several therapeutic targets, such as programmed death (PD-1) and its ligand programmed cell death ligand 1 (PD-L1). Over the past 3 years, immune checkpoint inhibitors targeting the PD-1-PD-L1 axis have demonstrated the ability to achieve durable objective responses in trials of patients with metastatic disease. If the current momentum continues, immunotherapy is poised to change the landscape of muscle-invasive bladder cancer treatment, promising improved survival outcomes for patients with this disease.

Landmarks in the treatment of muscle-invasive bladder cancer.

Between 25 and 80 % of patients undergoing a low or very low anterior resection will suffer postoperatively, from a constellation of symptoms including fecal urgency, frequent bowel movements, bowel fragmentation and incontinence, collectively referred to as the low anterior resection syndrome (LARS). The etiology of LARS is multifactorial with the potential of sphincter injury during anastomosis construction, alterations in anorectal physiology, the development of a pudendal neuropathy, and a lumbar plexopathy with exacerbation of symptoms if there is associated anastomotic sepsis or the use of adjuvant and neoadjuavnt therapies. The symptoms of LARS may be obviated in part by the construction of a neorectal reservoir which may take the form of a colonic J-pouch, a transverse coloplasty, or a side-to-end anastomosis. This review outlines the factors contributing to LARS symptomatology along with the short- and medium-term functional results of comparative trials with the different types of neorectal reconstructions.

Low anterior resection syndrome (LARS): cause and effect and reconstructive considerations.

Late radiation-induced bowel complications were studied in 218 patients treated for localized carcinoma of the prostate by radical radiotherapy at the Prince of Wales Hospital between 1980 and 1986. Mild to moderate toxicity was seen in 38 cases, and severe toxicity requiring surgery occurred in 3 patients. The total actuarial complication rate (by 5 years) for all grades was 24% and for severe complications was 1.8%. Significant patient-related risk factors were older age at the time of radiotherapy (p = 0.035) and a previous history of abdominal operations (p = 0.028). Among treatment-related risk factors only inclusion of the whole pelvis in the irradiated volume had a significant association with this complication (p = 0.015). The risk of bowel complications was not related to the total radiation dose or to the use of interstitial implants as employed in this series.

Bowel complications after radiotherapy for carcinoma of the prostate: the volume effect.

The treatment results for invasive transitional cell carcinoma (TCC) of the bladder were assessed in a series of 390 patients referred to the Department of Radiation Oncology at the Prince of Wales Hospital, Sydney, Australia, during the period 1977 to 1988. These patients were managed by one of two strategies: cystectomy (87 patients) and radiation therapy (303 patients). Actuarial survival rates (death from any cause) were determined and comparisons were made using log-rank tests and Cox regression analyses. The mean follow-up time was 7.6 years. Independent prognostic factors for shorter survival were: the presence of a ureteric obstruction (P less than 0.001), increasing clinical stage (P less than 0.001), increasing patient age (P = 0.003), and earlier year of presentation (P = 0.008). Comparison of the two strategies indicated no significant difference in overall survival after adjusting for imbalances in prognostic factors (P = 0.007 unadjusted; P = 0.29 adjusted). The slightly longer survival of 46 patients from 1983 onward who received primary systemic chemotherapy (compared with 149 patients not given chemotherapy) was not statistically significant (P = 0.12 unadjusted; P = 0.56 adjusted for prognostic factors). The 5-year actuarial rates of severe complications were 8.0% after cystectomy and 5.3% after radiation therapy. In 303 patients treated by definitive radiation therapy, the 5-year actuarial rate of freedom from bladder failure for all clinical tumor stages was 44% (Tx, 67%; T1, 45%; T2, 56%; T3, 39%; and T4, 39%). These results suggest that definitive radiation therapy is a viable alternative to radical cystectomy for patients with invasive TCC of the bladder.

The management of invasive transitional cell carcinoma of the bladder. Results of definitive and preoperative radiation therapy in 390 patients treated at the Prince of Wales Hospital, Sydney, Australia.

Between 1980 and 1986 a total of 218 patients with localised prostatic carcinoma received radical pelvic radiotherapy at The Prince of Wales Hospital, Sydney. The mean follow-up time was 4.6 years. The five-year actuarial overall survival rate was 63% (death from all causes) and the five-year cancer-specific survival rate was 73% (death from or with prostate cancer). The overall survival was significantly worse with more advanced clinical stage of the disease (P = 0.003) and with poor histological differentiation of the tumour (P = 0.001). The five-year actuarial rate for local control of tumour in the pelvis was 84%. Late treatment-related complications (occurring or persisting beyond six months) were mild or moderate and the majority settled with conservative management. Only five patients experienced severe complications (necessitating surgical treatment). Of 42 patients with normal potency documented before radiotherapy who were not subsequently hormonally manipulated 23 (55%) retained potency at two years. These results for definitive radiotherapy for localised prostatic carcinoma indicate good local control with minimal morbidity and compare favourably with other published results.

Results of radiotherapy for localised prostatic carcinoma treated at the Prince of Wales Hospital, Sydney.

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Bowel complications after radiotherapy for carcinoma of the prostate: the volume effect.

The management of invasive transitional cell carcinoma of the bladder. Results of definitive and preoperative radiation therapy in 390 patients treated at the Prince of Wales Hospital, Sydney, Australia.

Results of radiotherapy for localised prostatic carcinoma treated at the Prince of Wales Hospital, Sydney.