Can subcentimetre ultrasound detected angiomyolipomas be safely disregarded?

AIM: To optimise follow-up by dismissing lesions on baseline ultrasound (US) if renal lesions conform to US criteria of an angiomyolipoma (AML). METHOD AND MATERIALS: The present study was a 10-year retrospective review of patients who were found to have incidental hyperechoic renal lesions on US to ascertain the outcome from subsequent imaging, clinical encounters, and cancer registrations. Exclusions included renal calculi, tuberous sclerosis, Von-Hippel-Lindau, or a known cancer. RESULTS: After excluding 39 patients, 1,493 patients were identified. One hundred and sixty had more than one lesion with 87 patients having bilateral lesions. Regardless of indication, 889 patients had subsequent imaging within 5 years (59.5%). The average size of all AMLs was 13.2 mm. In the group with lesions that were <10 mm (807), 438 had imaging follow-up with an average follow-up time of 1.5 years. Mean lesion size in this group was 7 mm, with an average increase of <0.5 mm on follow-up. No lesions were found to be malignant on subsequent imaging nor did any of these patients have a subsequent renal cancer diagnosis registered at local multidisciplinary team meetings. CONCLUSION: No incidental subcentimetre hyperechoic renal lesion with imaging characteristics of an AML demonstrated significant growth or developed into a malignancy on follow-up.

Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer.

BACKGROUND: Robust data on patient-reported outcome measures comparing treatments for clinically localized prostate cancer are lacking. We investigated the effects of active monitoring, radical prostatectomy, and radical radiotherapy with hormones on patient-reported outcomes. METHODS: We compared patient-reported outcomes among 1643 men in the Prostate Testing for Cancer and Treatment (ProtecT) trial who completed questionnaires before diagnosis, at 6 and 12 months after randomization, and annually thereafter. Patients completed validated measures that assessed urinary, bowel, and sexual function and specific effects on quality of life, anxiety and depression, and general health. Cancer-related quality of life was assessed at 5 years. Complete 6-year data were analyzed according to the intention-to-treat principle. RESULTS: The rate of questionnaire completion during follow-up was higher than 85% for most measures. Of the three treatments, prostatectomy had the greatest negative effect on sexual function and urinary continence, and although there was some recovery, these outcomes remained worse in the prostatectomy group than in the other groups throughout the trial. The negative effect of radiotherapy on sexual function was greatest at 6 months, but sexual function then recovered somewhat and was stable thereafter; radiotherapy had little effect on urinary continence. Sexual and urinary function declined gradually in the active-monitoring group. Bowel function was worse in the radiotherapy group at 6 months than in the other groups but then recovered somewhat, except for the increasing frequency of bloody stools; bowel function was unchanged in the other groups. Urinary voiding and nocturia were worse in the radiotherapy group at 6 months but then mostly recovered and were similar to the other groups after 12 months. Effects on quality of life mirrored the reported changes in function. No significant differences were observed among the groups in measures of anxiety, depression, or general health-related or cancer-related quality of life. CONCLUSIONS: In this analysis of patient-reported outcomes after treatment for localized prostate cancer, patterns of severity, recovery, and decline in urinary, bowel, and sexual function and associated quality of life differed among the three groups. (Funded by the U.K. National Institute for Health Research Health Technology Assessment Program; ProtecT Current Controlled Trials number, ISRCTN20141297 ; ClinicalTrials.gov number, NCT02044172 .).

A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design.

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

Carbonic anhydrase IX expression and outcome after radiotherapy for muscle-invasive bladder cancer.

AIMS: Carbonic anhydrase IX (CA IX) expression has been described as an endogenous marker of hypoxia in solid neoplasms. Furthermore, CA IX expression has been associated with an aggressive phenotype and resistance to radiotherapy. We assessed the prognostic significance of CA IX expression in patients with muscle-invasive bladder cancer treated with radiotherapy. MATERIALS AND METHODS: A standard immunohistochemistry technique was used to show CA IX expression in 110 muscle-invasive bladder tumours treated with radiotherapy. Clinicopathological data were obtained from medical case notes. RESULTS: CA IX immunostaining was detected in 89 ( approximately 81%) patients. Staining was predominantly membranous, with areas of concurrent cytoplasmic and nuclear staining and was abundant in luminal and perinecrotic areas. No significant correlation was shown between the overall CA IX status and the initial response to radiotherapy, 5-year bladder cancer-specific survival or the time to local recurrence. CONCLUSIONS: The distribution of CA IX expression in paraffin-embedded tissue sections seen in this series is consistent with previous studies in bladder cancer, but does not provide significant prognostic information with respect to the response to radiotherapy at 3 months and disease-specific survival after radical radiotherapy.

The management of lymph node metastasis from bladder cancer.

AIM: The presence of pelvic lymph node metastasis from bladder cancer has traditionally been associated with a very poor prognosis. The aim of this paper is to review the literature with regard to the management of patients with nodal disease, particularly gross nodal metastasis and suggest a strategy for management of these patients. METHODS: We performed a literature search in the PubMed database and the reference lists of relevant papers describing the management of locally advanced bladder cancer. FINDINGS: There are no randomised studies relating specifically to the management of nodal metastasis in bladder cancer. It is clear however that a significant number of patients with micrometastatic nodal disease may be cured. Few studies exist which address the management of patients with gross nodal disease and consist of series from a limited number of institutions. In patients with gross nodal disease detected pre-operatively or at the time of surgery, a multimodality approach consisting of surgery, chemotherapy and possibly radiotherapy seems appropriate. The prognosis of such patients relates to the pathological stage of the primary tumour and the degree of lymph node involvement. In addition a good response to neoadjuvant chemotherapy may identify patients who are likely to survive longer. CONCLUSIONS: The prognosis for patients with gross nodal disease from bladder cancer is poor although cure may be possible in a small number of patients. In such cases a multimodality approach is appropriate and management decisions should be made on an individual patient basis.

Concomitant chemoradiotherapy for muscle-invasive bladder cancer: the way forward for bladder preservation?

Muscle-invasive bladder cancer is a common malignancy with a high mortality rate. Despite ongoing debates about the optimal primary intervention, radical cystectomy remains the cornerstone of first-line therapy in many institutions. Over the past decade, bladder-preserving strategies involving transurethral resection (TUR), chemotherapy and radiotherapy have evolved. However, the advantage of these approaches over radiation treatment as monotherapy has yet to be fully evaluated. In other tumour models, most notably cervical and anal cancer, radiation and chemotherapy delivered concomitantly have resulted in significant survival advantages. Here, we consider the potential value of this approach in the treatment of invasive bladder cancer. Concomitant chemoradiotherapy is currently the mainstay of several bladder-preserving programmes reported in the medical literature. Overall, local control and survival rates compare favourably with contemporary cystectomy series; however, difficulties in drawing valid conclusions are highlighted. Concomitant chemoradiotherapy may have a role in the management of certain patient subgroups, and the debate should remain open. Further large-scale randomised trials are needed, and information regarding bladder function and quality of life after treatment is lacking at present. The importance of close follow-up and prompt salvage cystectomy is emphasised.

Prolonged suction drainage prevents serous wound discharge after cardiac surgery.

A series of 180 patients was randomised to two groups after median sternotomy performed for cardiac surgery in order to evaluate the effect of suction drainage on serous wound discharge. In group A all wounds were drained using two conventional mediastinal drains, while in group B one suction drain and one conventional mediastinal drain were employed. Five patients developed serous wound discharge in group B compared with 14 in group A (chi 2, P < 0.02). There were no significant differences between the rates of major wound infection (group A, n = 1; group B, n = 1) or the incidence of postoperative pericardial effusion assessed by echocardiography (group A, n = 10; group B, n = 5).

Complication of treatment of carcinoma in situ of the bladder with photodynamic targeted cystodiathermy.

We report two cases of bladder contracture following photodynamic or 'blue light' detection and cystodiathermy for bladder carcinoma in situ. These patients were unsuitable for treatment with immunotherapy/chemotherapy or had disease recurrence following such treatment. Radical cystectomy was not a treatment option in either patient. Each underwent serial photodynamic cystodiathermy over a three-year period. Neither patient developed muscle invasive disease. However, treatment resulted in contracture of the bladder and incontinence of urine. Patients need to be fully aware of this potential complication in order to make informed choices about their care.

Results of a quantitative survey to explore both perceptions of the purposes of follow-up and preferences for methods of follow-up delivery among service users, primary care practitioners and specialist clinicians after cancer treatment.

AIMS: To ascertain perceptions of reasons for follow-up after cancer treatment among service users (patients and carers), primary care practitioners and specialist clinicians (doctors and specialist nurses) and to identify levels of preference for different models of follow-up and the effect of an individual's experience on preferred models. MATERIALS AND METHODS: A national survey designed to meet the needs of each key respondent group was carried out after a structured literature review, an extensive consultation process and a pilot scheme. Respondents were asked to assess their degree of preference for 10 pre-selected indications for follow-up. Eight models of follow-up were also identified and respondents were asked to state their experience and preference for each type. The questionnaire was distributed nationally via the 34 cancer networks in England and was available both online and in hard copy (postal). The uptake for the electronic format was in the main by primary care practitioners and specialist clinicians. Service users preferred the paper (postal) format. The survey was also publicised through the primary care and patient partnership forums at a Cancer Network Development event. RESULTS: In total, 2928 responses were received, comprising service users (21% of the sample), primary care practitioners (32%) and specialist clinicians (47%). Eighty-six per cent of responses were received from the 10 strategic health authorities in England, with the remaining 14% from Scotland, Wales and The Isle of Man. The responses from Scotland, Wales and the Isle of Man generally occurred where they interfaced with English cancer networks or had been engaged through word of mouth by colleagues. Among all respondents the main aims of cancer follow-up were considered to be: (1) to monitor for early complications after treatment; (2) to detect recurrences early; (3) to detect late effects of treatment. The most commonly experienced method of follow-up among all respondent groups was outpatient review with a doctor. This was considered to be the most preferred follow-up option among service users (86%). The least preferred option among service users was postal follow-up (32%). Primary care practitioners and specialist clinicians were more likely than service users to have experienced alternative methods of follow-up, such as telephone follow-up, self-triggered referral and non-specialist follow-up. These models were highly rated by those who had experience of them. CONCLUSIONS: There was a reasonable level of consensus between service users, primary care practitioners and specialist clinicians as to the reasons for follow-up. Service users seemed to have higher expectations of follow-up, particularly in relation to detecting recurrences early. As respondents were more likely to prefer a method of follow-up delivery that they had experienced than one they had not; there could be resistance to change from established methods to new methods without adequate explanation. This suggests that the communication of new methods could be critical to their successful introduction.

A randomized trial of radical radiotherapy for the management of pT1G3 NXM0 transitional cell carcinoma of the bladder.

PURPOSE: We conducted a multicenter randomized trial in the United Kingdom to determine the efficacy of radical radiotherapy in reducing the incidence of progression of pT1G3 transitional cell carcinoma of the bladder to muscle invasive disease and subsequent disease fatality. MATERIALS AND METHODS: Patients with a new diagnosis of pT1G3 NXM0 transitional cell carcinoma with unifocal disease and no carcinoma in situ (group 1), or with multifocal disease and/or carcinoma in situ (group 2) were eligible for the trial. Patients in group 1 were randomized between observation and radiotherapy to the bladder, and in group 2 between intravesical therapy and radiotherapy. RESULTS: From September 1991 to February 2003 a total of 210 patients from 37 centers in the United Kingdom were entered into the study. There were 77 patients in group 1 and 133 patients in group 2, and 6 patients were excluded from analysis because they were found to have pT2 disease by the reference pathologist. No evidence of an advantage with radiotherapy was found in terms of progression-free interval (hazard ratio 1.07; 95% CI 0.65, 1.74; p = 0.785), progression-free survival (hazard ratio 1.35; 95% CI 0.92, 1.98; p = 0.133) or overall survival (hazard ratio 1.32; 95% CI 0.86, 2.04; p = 0.193). CONCLUSIONS: To our knowledge this is the largest randomized trial performed in patients with pT1G3 disease for which 210 patients were recruited during 11 years. There is no evidence that radiotherapy is better than more conservative treatment. The prognosis of this group of patients appears to be poor irrespective of treatment and new treatment strategies need to be investigated.

The transanal resectoscope: an under-used instrument?

The use of the urological resectoscope in the treatment of rectal tumours has been described in detail. We report the use of the purpose built transanal resectoscope in the treatment of 34 patients. Fourteen patients had villous adenomas and all but one were relieved of symptoms. Of 20 patients with rectal carcinoma, three presented with acute intestinal obstruction and three had rectal stump recurrences. Palliation was excellent in patients with general symptoms, but the results were disappointing for rectal stump recurrences. Transanal resection (TAR) is a novel form of treatment for patients with rectal obstruction. Two patients in this study had their obstruction successfully relieved by transanal resection alone. This allowed formal bowel preparation and full pre-operative assessment. We feel that this technique is under-used and that the results of treatment justify more widespread acceptance of the procedure.

Pyeloureterostomy in the management of renal allograft ureteral complications: an alternative technique.

Pyeloureterostomy is the standard procedure for reconstructing renal allograft ureteral complications. Most reports describe an end-to-end technique with or without native nephrectomy. An alternative is an end-to-side anastomosis, leaving the native ureter in continuity. We report our experience with the latter method. Since July 1983, 437 renal transplantations have been performed at our institution. End-to-side pyeloureterostomy has been used in 5 cases for urological reconstruction after renal transplantation following ureteral ischemic necrosis or stenosis. In 1 patient the native kidneys had been removed several years previously but in the remaining 4 the native kidneys were left in situ. There have been no significant complications following this procedure. We believe that by not significantly mobilizing, ligating or dividing the native ureter the chance of anastomotic breakdown due to ischemia may be decreased.

Clam enterocystoplasty in general urological practice.

A series of 45 patients (31 female) underwent clam enterocystoplasty for urgency and incontinence. The majority had detrusor instability. Prolonged conservative treatment had failed in all cases. Improvement occurred in 71% and those younger than 30 years had better overall results; 29% remained incontinent, with 9% requiring a urinary diversion. Many patients did not achieve maximum benefit until 9 months post-operatively. Surgery had no statistically significant effect on any urodynamic parameter and post-operative complications were common. The operation was performed in either the coronal (19) or the sagittal plane (26); this did not influence results. In general, surgery was found to be technically simpler in the sagittal group and it is recommended that this becomes the standard procedure. We feel that this operation involves major surgery and should only be offered with reluctance.

Measurements using the alkaline comet assay predict bladder cancer cell radiosensitivity.

In the UK, the two main treatments of invasive bladder cancer are radiotherapy or cystectomy. However, approximately 50% of patients undergoing radiotherapy fail to respond. If tumour radiosensitivity could be predicted in advance, it may be possible to improve control rates significantly by selecting for radiotherapy those patients whose tumours are radiosensitive. Additionally, patients who would benefit from surgery would be identified earlier. The alkaline comet assay (ACA) is a sensitive method for the detection of DNA strand break damage in cells. In the present study, using six bladder cancer cell lines of differing radiosensitivities, cell survival was compared to the manifestation of radiogenic DNA damage as assessed by ACA. For all the cell lines, the extent of comet formation strongly correlates with cell killing (R2>0.96), with a greater response being noted in radiosensitive cells. In repair studies, measures of residual damage correlate with survival fraction at 2 Gy (R2>0.96), but for only five of the cell lines. Finally, cells from human bladder tumour biopsies reveal a wide range of predicted radiosensitivies as determined by ACA. Overall, these studies demonstrate ACA to be a good predictive measure of bladder cancer cell radiosensitivity at low dose, with potential clinical application.