Current management of radiation cystitis after pelvic radiotherapy: a systematic review.

INTRODUCTION: We aimed to summarize current literature about radiation cystitis treatments, providing physician of a summary of current management options. EVIDENCE ACQUISITION: A systematic literature review searching on PubMed (Medline), Scopus, and Web of Science databases was performed in March 2021. PRISMA guidelines were followed. Population consisted of patients with a diagnosis of radiation cystitis after pelvic radiotherapy (P). We focused our attention on different treatments, such as conservative or surgical one (I). Single or multiple arms studies were deemed eligible with no mandatory comparison (C). Main outcomes of interest were symptoms control and adverse events rates (O). EVIDENCE SYNTHESIS: The search identified 1194 records. Of all, four studies focused on the use of hyperbaric oxygen therapy showing complete response rates ranging from 52% to 87% approximately. Oral administration of cranberry compounds was investigated in one study showing no superiority to placebo. Intravesical instillation of different compounds were investigated in five studies showing the highest complete response rates after alum (60%) and formalin administration (75%). Endoscopic conservative surgical treatments (fibrin glue or vaporization) also showed 75% complete response rates. In patients who did not respond to conservative treatments robotic cystectomy is feasible with overall complication rates of about 59.3% at 90 days. CONCLUSIONS: Radiotherapy induced cystitis is an under-reported condition after pelvic radiotherapy. Several treatments have been proposed, but in up to 10% of cases salvage cystectomy is necessary. A stepwise approach, with progressive treatment aggressiveness is recommended.

Treatment of osteoporosis secondary to hypogonadism in prostate cancer patients: a prospective randomized multicenter international study with denosumab vs. alendronate.

BACKGROUND: Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT. METHODS: A total of 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer were enrolled. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg/week) for 2 years. All patient received supplemental vitamin D (600 IU/day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), bone mineral density, fracture incidence, Visual Analogue Scale score for back pain, and Short Form-8 health survey score for health-related quality of life. RESULTS: In the denosumab study group, level of BTMs for bone formation were significantly increased from baseline at all time points during the study (P<0.001); in the alendronate study group level of BTMs for bone formation were increased too (P>0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24 months were 5.6% with denosumab vs. -1.1% with alendronate (P<0.001). CONCLUSIONS: Denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.

Bipolar vs monopolar transurethral resection of the prostate: evaluation of the impact on overall sexual function in an international randomized controlled trial setting.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The effect of TURP on overall sexual function and particularly erectile function (EF) is controversial with conflicting results based on a low level of evidence. The effects of monopolar and bipolar TURP (M-TURP and B-TURP, respectively) on EF are similar, as has been shown in a few non-focused randomized control trials (RCTs). For the first time, the present study offers focused results of a comparative evaluation of the effects of B-TURP and M-TURP on overall sexual function, as quantified with the International Index of Erectile Function Questionnaire (IIEF-15) in an international, multicentre, double-blind RCT setting. OBJECTIVE: To compare monopolar and bipolar transurethral resection of the prostate (M-TURP and B-TURP, respectively) using a true bipolar system, for the first time in an international multicentre double-blind randomized controlled trial focusing on the overall sexual function quantified with the International Index of Erectile Function Questionnaire (IIEF-15). Other baseline/perioperative parameters potentially influencing erectile function (EF) after TURP were secondarily investigated. MATERIALS AND METHODS: From July 2006 to June 2009, consecutive TURP candidates with benign prostatic obstruction were prospectively recruited in four academic urological centres, randomized 1:1 into M-TURP/B-TURP arms and followed up at 6 weeks, 6 and 12 months after surgery. In all, 295 eligible patients were enrolled. Overall sexual function was quantified using self-administered IIEF-15 at baseline and at each subsequent visit. Total IIEF/domain scores were calculated and EF score classified erectile dysfunction severity. Differences in erectile dysfunction severity at each visit compared with baseline (EF evolution), classified patients into 'improved', 'stable' or 'deteriorated'. Pre-postoperative IIEF/domain scores and differences in the distribution of EF evolution were compared between arms throughout follow-up. RESULTS: In all, 279 patients received the allocated intervention; 218/279 patients (78.1%) provided complete IIEF-15 data at baseline and were considered in sexual function analysis. Complete IIEF-15 data were available from 193/218 (88.5%), 186/218 (85.3%) and 179/218 (82.1%) patients at 6 weeks, 6 months and 12 months, respectively. Sexual function did not differ significantly between arms during follow-up (scores: IIEF, P = 0.750; EF, P = 0.636; orgasmic function, P = 0.868; sexual desire, P = 0.735; intercourse satisfaction, P = 0.917; overall satisfaction, P = 0.927). Resection type was not a predictor of any sexual function changes observed. Distribution of EF evolution did not differ between arms at any time (M-TURP vs B-TURP at 12 months: improved, 23/87 [26.4%] vs 18/92 [19.6%]; stable, 53/87 [60.9%] vs 56/92 [60.8%]; deteriorated, 11/87 [12.7%] vs 18/92 [19.6%]; P = 0.323). CONCLUSION: There were no differences between M-TURP/B-TURP in any aspect of sexual function.

Midterm results from an international multicentre randomised controlled trial comparing bipolar with monopolar transurethral resection of the prostate.

BACKGROUND: Pooled data from randomised controlled trials (RCTs) with short-term follow-up have shown a safety advantage for bipolar transurethral resection of the prostate (B-TURP) compared with monopolar TURP (M-TURP). However, RCTs with follow-up >12 mo are scarce. OBJECTIVE: To compare the midterm safety/efficacy of B-TURP versus M-TURP. DESIGN, SETTING, AND PARTICIPANTS: From July 2006 to June 2009, TURP candidates with benign prostatic obstruction were consecutively recruited in four centres, randomised 1:1 into the M-TURP or the B-TURP arm and regularly followed up to 36 mo postoperatively. A total of 295 patients were enrolled. INTERVENTION: M-TURP or B-TURP using the AUTOCON II 400 electrosurgical unit. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Safety was estimated by complication rates with a special emphasis on urethral strictures (US) and bladder neck contractures (BNCs) recorded during the short-term (up to 12 mo) and midterm (up to 36 mo) follow-up. Efficacy quantified by changes in maximum urine flow rate, postvoid residual urine volume, and International Prostate Symptom Score was compared with baseline, and reintervention rates in each arm were also evaluated. RESULTS AND LIMITATIONS: A total of 279 patients received treatment after allocation. Mean follow-up was 28.8 mo. A total of 186 of 279 patients (66.7%) completed the 36-mo follow-up. Posttreatment withdrawal rates did not differ significantly between arms. Safety was assessed in 230 patients (82.4%) at a mean follow-up of 33.4 mo. Ten US cases were seen in each arm (M-TURP vs B-TURP: 9.3% vs 8.2%; p=0.959); two versus eight BNC cases (M-TURP vs B-TURP: 1.9% vs 6.6%; p=0.108) were collectively detected at the midterm follow-up. Resection type was not a significant predictor of the risk of US/BNC formation. Efficacy was similar between arms and durable. A total of 10 of 230 patients (4.3%) experienced failure to cure and needed reintervention without significant differences between arms. High overall reintervention rates, withdrawal rates, and sample size determination not based on US/BNC rates represent potential limitations. CONCLUSIONS: The midterm safety and efficacy of B-TURP and M-TURP are comparable. TRIAL REGISTRATION: Netherlands Trial Register, NTR703 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=703).

Results from an international multicentre double-blind randomized controlled trial on the perioperative efficacy and safety of bipolar vs monopolar transurethral resection of the prostate.

OBJECTIVE: To compare the perioperative efficacy and safety of bipolar (B-) and monopolar transurethral resection of the prostate (M-TURP) in an international multicentre double-blind randomized controlled trial using the bipolar system AUTOCON(®) II 400 ESU for the first time. PATIENTS AND METHODS: From July 2006 to June 2009, consecutive transurethral resection of the prostate (TURP) candidates with benign prostatic obstruction were prospectively recruited in four academic urological centres, randomized 1:1 into an M-TURP or B-TURP arm and followed up for 6 weeks after surgery. A total of 295 eligible patients were enrolled. Of these, 279 patients received treatment (M-TURP, n= 138; B-TURP, n= 141) and were analysed for immediate postoperative outcomes and perioperative safety. In all, 268 patients (M-TURP, n= 129; B-TURP, n= 139) were analysed for efficacy, which was quantified using changes in maximum urinary flow rate, postvoid residual urine volume and International Prostate Symptom Score at 6 weeks compared with baseline. Safety was estimated using sodium and haemoglobin level changes immediately after surgery and perioperative complication occurrence graded according to the modified Clavien classification system. Secondary outcomes included operation-resection time, resection rate, capsular perforation and catheterization time. RESULTS: No significant differences were detected between each study arm except that postoperative decreases in sodium levels favoured B-TURP (-0.8 vs -2.5 mmol/L, for B-TURP and M-TURP, respectively; P= 0.003). The lowest values were 131 mmol/L (B-TURP) and 106 mmol/L (M-TURP). Nine patients ranged between 125 and 130 mmol/L and the values for three patients were <125 mmol/L after M-TURP. The greatest decrease was 9 mmol/L after B-TURP (two patients). In nine patients (M-TURP) the decrease was between 9 and 34 mmol/L. These results were not translated into a significant difference in TUR-syndrome rates (1/138: 0.7% vs 0/141: 0.0%, for M-TURP and B-TURP, respectively; P= 0.495). CONCLUSIONS: In contrast to the previous available evidence, no clinical advantage for B-TURP was shown. Perioperative efficacy, safety and secondary outcomes were comparable between study arms. The potentially improved safety of B-TURP that is attributed to the elimination of dilutional hyponatraemia risk, a risk still present with M-TURP, did not translate into a significant clinical benefit in experienced hands.

Background to and management of treatment-related bone loss in prostate cancer.

Prostate cancer is a common disease among older men. Androgen suppression by either orchiectomy or administration of luteinising hormone-releasing hormone (LHRH) analogues is the mainstay of treatment. Since the use of prostate-specific antigen (PSA) serum testing has become widespread, however, the timing of endocrine therapy has expanded considerably to include patients with limited involvement of extraprostatic sites and patients presenting an isolated elevation of PSA after radical treatments. These patients are expected to be treated for a long time, since they have a rather low risk of disease progression and there is no recommended time limit for LHRH analogue therapy. The long-term adverse effects of androgen deprivation therapy, therefore, deserve more attention than they have received in the past. Osteoporosis represents a special concern for men with prostate cancer receiving androgen deprivation therapy. The rate of bone loss in these men seems to markedly exceed that associated with menopause in women, and fractures occur more frequently than in the healthy elderly male population. Serial bone mineral density (BMD) evaluation could allow the detection of patients with prostate cancer who are at greater risk of osteoporosis and adverse skeletal events after androgen deprivation therapy, such as patients already osteopenic or osteoporotic at baseline and men with rapid bone loss during treatment. BMD evaluated during treatment could also be a potential surrogate parameter of antiosteoporotic therapeutic efficacy. Treatment of bone loss induced by androgen deprivation comprises general prevention measures, antiosteoporotic drugs and the use of alternative endocrine therapies. Optimising lifestyle and diet is important, although it cannot completely prevent bone loss. Patients with nonsevere bone disease may benefit from calcium and vitamin D supplements. Men who are osteoporotic before androgen deprivation or men becoming osteoporotic during treatment and/or experiencing adverse skeletal events may also require bisphosphonates. The effectiveness of these drugs in preventing fractures has been shown in a single randomised study involving patients with osteoporosis, but it has not yet been established in a prostatic cancer population without bone metastases given androgen deprivation therapy. Different forms of endocrine therapy such as low-dose estrogens, antiandrogens and intermittent androgen ablation are under investigation. They could offer the advantage of avoiding (or limiting) treatment-related bone loss. In our opinion, however, the data available so far are not robust enough to recommend these alternative endocrine therapies instead of standard androgen deprivation in routine clinical practice.