Timing of radiotherapy (RT) after radical prostatectomy (RP): long-term outcomes in the RADICALS-RT trial (NCT00541047).

BACKGROUND: The optimal timing of radiotherapy (RT) after radical prostatectomy for prostate cancer has been uncertain. RADICALS-RT compared efficacy and safety of adjuvant RT versus an observation policy with salvage RT for prostate-specific antigen (PSA) failure. PATIENTS AND METHODS: RADICALS-RT was a randomised controlled trial enrolling patients with ≥1 risk factor (pT3/4, Gleason 7-10, positive margins, preoperative PSA≥10 ng/ml) for recurrence after radical prostatectomy. Patients were randomised 1:1 to adjuvant RT ('Adjuvant-RT') or an observation policy with salvage RT for PSA failure ('Salvage-RT') defined as PSA≥0.1 ng/ml or three consecutive rises. Stratification factors were Gleason score, margin status, planned RT schedule (52.5 Gy/20 fractions or 66 Gy/33 fractions) and treatment centre. The primary outcome measure was freedom-from-distant-metastasis (FFDM), designed with 80% power to detect an improvement from 90% with Salvage-RT (control) to 95% at 10 years with Adjuvant-RT. Secondary outcome measures were biochemical progression-free survival, freedom from non-protocol hormone therapy, safety and patient-reported outcomes. Standard survival analysis methods were used; hazard ratio (HR)<1 favours Adjuvant-RT. RESULTS: Between October 2007 and December 2016, 1396 participants from UK, Denmark, Canada and Ireland were randomised: 699 Salvage-RT, 697 Adjuvant-RT. Allocated groups were balanced with a median age of 65 years. Ninety-three percent (649/697) Adjuvant-RT reported RT within 6 months after randomisation; 39% (270/699) Salvage-RT reported RT during follow-up. Median follow-up was 7.8 years. With 80 distant metastasis events, 10-year FFDM was 93% for Adjuvant-RT and 90% for Salvage-RT: HR=0.68 [95% confidence interval (CI) 0.43-1.07, P=0.095]. Of 109 deaths, 17 were due to prostate cancer. Overall survival was not improved (HR=0.980, 95% CI 0.667-1.440, P=0.917). Adjuvant-RT reported worse urinary and faecal incontinence 1 year after randomisation (P=0.001); faecal incontinence remained significant after 10 years (P=0.017). CONCLUSION: Long-term results from RADICALS-RT confirm adjuvant RT after radical prostatectomy increases the risk of urinary and bowel morbidity, but does not meaningfully improve disease control. An observation policy with salvage RT for PSA failure should be the current standard after radical prostatectomy. TRIAL IDENTIFICATION: RADICALS, RADICALS-RT, ISRCTN40814031, NCT00541047.

Prostate artery embolisation: an all-comers, single-operator experience in 159 patients with lower urinary tract symptoms, urinary retention, or haematuria with medium-term follow-up.

AIM: To describe the authors' experience with prostate artery embolisation (PAE) to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) or refractory haematuria of prostatic origin (RHOPA). MATERIALS AND METHODS: PAE was attempted in 159 patients. Procedural details, pre/post-PAE symptom scores, and pre/post-PAE magnetic resonance imaging (MRI) data were recorded. Statistical analysis was performed to determine clinical outcomes and factors predicting clinical success. RESULTS: Technical success was achieved in 156 patients. In patients with LUTS, the International Prostate Symptom Score (IPSS) improved from a mean of 22 at baseline to 9.5 at 6-months post-PAE, then to 10.7, 10, 11.3, and 11 at 1, 2, 3, and 4 years. The quality of life (QoL) score improved from 4.6 at baseline to 2, 2.2, 2.4, 3.1, and 2.5 at the same time points. The International Index of Erectile Function (IIEF-5) scores remained stable. There was no significant difference in IPSS between bilateral or unilateral embolisation to 2 years, or between BPH alone or BPH with biopsy-proven prostate cancer to 3 years post-PAE. Percentage improvement in IPSS at 1 year correlated with percentage reduction in prostate volume on first post-PAE MRI. Percentage improvement in IPSS at 3 years correlated with initial IPSS. PAE facilitated urinary catheter removal in 13/24 patients in retention. PAE controlled bleeding in 12/12 patients with RHOPA. CONCLUSION: PAE is safe and effective in the management of symptomatic BPH. Patients with the highest baseline IPSS and reduction in prostate volume on first post-PAE MRI are likely to derive most benefit from embolisation.

Systematic review of prostate cancer risk and association with consumption of fish and fish-oils: analysis of 495,321 participants.

INTRODUCTION: Fish-oils have a potential role in inflammation, carcinogenesis inhibition and favourable cancer outcomes. There has been increasing interest in the relationship of diet with cancer incidence and mortality, especially for eicosapantaenoic acid (EPA) and docosahexaenoic acid (DHA). This systematic-analysis of the literature aims to review evidence for the roles of dietary-fish and fish-oil intake in prostate-cancer (PC) risk, aggressiveness and mortality. METHODS: A systematic-review, following PRISMA guidelines was conducted. PubMed, MEDLINE and Embase were searched to explore PC-risk, aggressiveness and mortality associated with dietary-fish and fish-oil intake. 37 studies were selected. RESULTS: A total of 495,321 (37-studies) participants were investigated. These revealed various relationships regarding PC-risk (n = 31), aggressiveness (n = 8) and mortality (n = 3). Overall, 10 studies considering PC-risk found significant inverse trends with fish and fish-oil intake. One found a dose-response relationship whereas greater intake of long-chain-polyunsaturated fatty acids increased risk of PC when considering crude odds-ratios [OR: 1.36 (95% CI: 0.99-1.86); p = 0.014]. Three studies addressing aggressiveness identified significant positive relationships with reduced risk of aggressive cancer when considering the greatest intake of total fish [OR 0.56 (95% CI 0.37-0.86)], dark fish and shellfish-meat (p < 0.0001), EPA (p = 0.03) and DHA (p = 0.04). Three studies investigating fish consumption and PC-mortality identified a significantly reduced risk. Multivariate-OR (95% CI) were 0.9 (0.6-1.7), 0.12 (0.05-0.32) and 0.52 (0.30-0.91) at highest fish intakes. CONCLUSIONS: Fish and fish-oil do not show consistent roles in reducing PC incidence, aggressiveness and mortality. Results suggest that the specific fish type and the fish-oil ratio must be considered. Findings suggest the need for large intervention randomised placebo-controlled trials.

Clinical presentation and initial management of black men and white men with prostate cancer in the United Kingdom: the PROCESS cohort study.

BACKGROUND: In the United States, Black men have a higher risk of prostate cancer and worse survival than do White men, but it is unclear whether this is because of differences in diagnosis and management. We re-examined these differences in the United Kingdom, where health care is free and unlikely to vary by socioeconomic status. METHODS: This study is a population-based retrospective cohort study of men diagnosed with prostate cancer with data on ethnicity, prognostic factors, and clinical care. A Delphi panel considered the appropriateness of investigations and treatments received. RESULTS: At diagnosis, Black men had similar clinical stage and Gleason scores but higher age-adjusted prostate-specific antigen levels (geometric mean ratio 1.41, 95% confidence interval (95% CI): 1.15-1.73). Black men underwent more investigations and were more likely to undergo radical treatment, although this was largely explained by their younger age. Even after age adjustment, Black men were more likely to undergo a bone scan (odds ratio 1.37, 95% CI: 1.05-1.80). The Delphi analysis did not suggest differential management by ethnicity. CONCLUSIONS: This UK-based study comparing Black men with White men found no evidence of differences in disease characteristics at the time of prostate cancer diagnosis, nor of under-investigation or under-treatment in Black men.

Pathways to diagnosis for Black men and White men found to have prostate cancer: the PROCESS cohort study.

Black men in England have three times the age-adjusted incidence of diagnosed prostate cancer as compared with their White counterparts. This population-based retrospective cohort study is the first UK-based investigation of whether access to diagnostic services underlies the association between race and prostate cancer. Prostate cancer was ascertained using multiple sources including hospital records. Race and factors that may influence prostate cancer diagnosis were assessed by questionnaire and hospital records review. We found that Black men were diagnosed an average of 5.1 years younger as compared with White men (P<0.001). Men of both races were comparable in their knowledge of prostate cancer, in the delays reported before presentation, and in their experience of co-morbidity and symptoms. Black men were more likely to be referred for diagnostic investigation by a hospital department (P=0.013), although general practitioners referred the large majority of men. Prostate-specific antigen levels were comparable at diagnosis, although Black men had higher levels when compared with same-age White men (P<0.001). In conclusion, we found no evidence of Black men having poorer access to diagnostic services. Differences in the run-up to diagnosis are modest and seem insufficient to explain the higher rate of prostate cancer diagnosis in Black men.

Permanent prostate brachytherapy: a century of technical evolution.

PURPOSE: To summarise the practical aspects of the development of techniques of interstitial permanent prostate brachytherapy (PPB) implantation. Prostate brachytherapy dates back to Pasteau's publication in 1913 describing the insertion of a radium capsule into the prostatic urethra to treat carcinoma of the prostate. Various implantation methods were employed but with unsatisfactory results until the development of the transrectal ultrasound in the 1980s. The subsequent two-stage Seattle technique allowed for a planned homogenous distribution of radioactive sources throughout the gland resulting in biochemical control comparable to surgical and external beam radiotherapy series. With the advent of advanced computer software and improved imaging, the technique has developed accordingly to a single stage procedure with on-table dosimetric assessment. The principles of targeting dose to the prostate while avoiding surrounding organs at risk remain as relevant today as nearly a century ago. There is an array of techniques to consider for the novice PPB provider. Whether the evolution of PPB techniques will translate into improved biochemical control is yet to be seen.

Using combined x-ray and MR imaging for prostate I-125 post-implant dosimetry: phantom validation and preliminary patient work.

Post-implantation dosimetry is an important element of permanent prostate brachytherapy. This process relies on accurate localization of implanted seeds relative to the surrounding organs. Localization is commonly achieved using CT images, which provide suboptimal prostate delineation. On MR images, conversely, prostate visualization is excellent but seed localization is imprecise due to distortion and susceptibility artefacts. This paper presents a method based on fused MR and x-ray images acquired consecutively in a combined x-ray and MRI interventional suite. The method does not rely on any explicit registration step but on a combination of system calibration and tracking. A purpose-built phantom was imaged using MRI and x-rays, and the images were successfully registered. The same protocol was applied to three patients where combining soft tissue information from MRI with stereoscopic seed identification from x-ray imaging facilitated post-implant dosimetry. This technique has the potential to improve on dosimetry using either CT or MR alone.

The RUDY study platform - a novel approach to patient driven research in rare musculoskeletal diseases.

BACKGROUND: Research into rare diseases is becoming more common, with recognition of the significant diagnostic and therapeutic care gaps. Registries are considered a key research methodology to address rare diseases. This report describes the structure of the Rare UK Diseases Study (RUDY) platform that aims to improve research processes and address many of the challenges of carrying out rare musculoskeletal disease research. RUDY is an internet-based platform with online registration, initial verbal consent, online capture of patient reported outcome measures and events within a dynamic consent framework. The database structure, security and governance framework are described. RESULTS: There have been 380 participants recruited into RUDY with completed questionnaire rates in excess of 50 %. There has been one withdrawal and two participants have amended their consent options. CONCLUSIONS: The strengths of RUDY include low burden for the clinical team, low research administration costs with high participant recruitment and ease of data collection and access. This platform has the potential to be used as the model for other rare diseases globally.

Laparoscopic ureteroneocystostomy for benign lower ureteric stricture: case study and literature review.

The surgical treatment of distal ureteric strictures depends on their length and aetiology. Laparoscopic procedures in this setting are uncommon. We describe a laparoscopic non-refluxing ureteroneocystostomy for a symptomatic distal ureteric stricture performed on a 26-year-old man. The operation was carried out successfully without complication. Blood loss was 100 ml with an operating time of 250 min. He was discharged on the fourth day and returned to work after 11 days. Retrograde ureterography and cystography after 1 month showed no evidence of obstruction or reflux. At 3 months, an intravenous urogram showed excellent drainage and at 6 months the patient remained asymptomatic. We advocate the use of laparoscopic ureteroneocystostomy for benign distal ureteric stricture refractory to endoscopic procedures. In symptomatic patients, it is a feasible, safe, minimally invasive procedure with all the added benefits of laparoscopy compared with open repair. A non-refluxing anastomosis is preferable. Reconstructive and intracorporeal suturing skills are needed to carry out this procedure.

A randomised trial of periprostatic local anaesthetic for transrectal biopsy.

Increasingly transrectal ultrasound and biopsy is performed for the detection of prostate cancer. We have conducted a randomised trial to evaluate whether the addition of periprostatic local anaesthetic injection reduces the discomfort of the procedure. A total of 64 patients who attended a specialised prostate clinic and were being evaluated for an elevated prostate-specific antigen agreed to participate in the trial and were randomly allocated to two groups. The intervention group received 10 ml of 1% lignocaine in the periprostatic tissue prior to biopsy and the control group underwent a standard biopsy. All patients had a sextant biopsy under ultrasound guidance. After the procedure, they were asked to determine the severity of the pain on a scale of 0-10 and the whether the quality of the pain was mild, moderate or severe. The responses were distributed normally. The groups were compared using Student's t-test. Pain severity showed no significant difference between the two groups (P=0.14). There was a trend towards a statistical difference (P=0.07) on the qualitative pain scale. In conclusion, no significant difference in overall discomfort in men having sextant biopsies was detected between the two groups, suggesting that the administration of local anaesthetic may not be as valuable as early reports have suggested.

Urine cytology: appropriate usage maximizes sensitivity and reduces cost.

OBJECTIVE: Urine cytology is costly because of the skilled manpower required for analysis. Inappropriate requests are a significant drain both financially and on the cytopathologist's time. The present study aimed at identifying the extent and cause of this misuse and reduce it. METHODS: An audit of urine cytology usage was undertaken using the hospital results reporting system to identify requests. Patient case notes were then obtained to gain further clinical information. Initially a 2-week period was analysed, following which departmental guidelines for requesting urine cytology were produced and circulated. The audit loop was then closed. RESULTS: Over the initial 2-week period, 117 urine cytology requests were received. Thirty-three per cent were inappropriate, either because they were from patients with benign disease or because of duplication. Following the education programme this number fell to 6%. Expenditure on unnecessary samples thus decreased from pounds 2418 to only pounds 310, giving an annual overall saving of pounds 55,000. CONCLUSION: Significant cost and time savings can be made if urine cytology is sent appropriately. Simple guidelines and staff education are the key to reducing inefficiency. Our findings have implications not just for cytopathology costs but for laboratory and radiology requests in general.

'Nerve-sparing' cystectomy and substitution cystoplasty in patients of either sex: limitations and techniques.

OBJECTIVES: To determine the limitations of cystectomy and orthotopic substitution cystoplasty in men and women with bladder cancer. PATIENTS AND METHODS: Cystectomy and orthotopic substitution cystoplasty were carried out in 79 patients (mean age 60 years, range 31-74, including eight women) who were followed for a mean of 7 years (range 1-13) to evaluate continence, potency and survival. RESULTS: Overall, 80% of the patients were continent without further treatment and 55% of the men who were potent before surgery remained so afterward. The best results were obtained with retrograde cystectomy in both sexes and are only achievable in women in this way. Continence was achieved more easily in women than in men, although pathological delineation of the tumour preoperatively and technical considerations per-operatively make both the selection and the procedure more demanding in women than in men. CONCLUSIONS: Cystectomy and orthotopic substitution cystoplasty is possible in patients of either sex and should be offered to all patients as an alternative to ileal conduit urinary diversion, unless preoperative assessment suggests that the urethra must be removed with the bladder, which is rare in men and uncommon in women. In such patients, a continent diversion may be the preferred option.

Ultrasound in renal carcinoma: an essential in follow-up.

A total of 115 patients underwent radical nephrectomy for renal carcinoma in this hospital between 1983 and 1990. Follow-up was available in 113 cases (mean 27 months, range 0-93). The overall actuarial survival was 66% at 2 years and 53% at 5 years. Fifty-three patients have been followed up with annual abdominal ultrasound over the last 2 years. Abnormal ultrasound scans were reported in 6 patients (11%) on follow-up. Two had para-aortic lymph node recurrence amenable to further surgery. One patient developed a metachronous tumour and a partial nephrectomy was carried out. Three patients had local recurrence not amenable to further surgery. Ultrasound and computed tomography have found an invaluable place in the pre-operative diagnosis and staging of renal carcinoma. Sixteen of 113 tumours were diagnosed by ultrasound or intravenous urography carried out for some other purpose; 8 were less than 5 cm in diameter and 12 were T category N0M0V0. The 2-year survival rate in this group was 85% (mean 30 months, range 19-67). We consider the routine follow-up of renal carcinoma with clinical examination and annual chest X-ray to be inadequate. The application of ultrasound in the follow-up of these patients has provided a valuable adjunct to our clinical practice. It has allowed the prompt diagnosis of lymph node recurrence or metachronous tumour amenable to secondary surgery with the potential for improved survival in this group of patients. We consider this to be the logical extension of the value of ultrasound in the pre-operative diagnosis of renal carcinoma.

Relative cytotoxicities of adriamycin and epirubicin in combination with lonidamine against human bladder cancer cell lines.

We have used a panel of bladder cancer cell lines to compare the toxicities of Adriamycin and epirubicin, two drugs used intravesically to treat superficial transitional cell cancer (TCC) of the bladder, alone and in combination with lonidamine, an agent known to be active against anthracycline-resistant disease. Comparing concentrations reducing colony-forming ability by 50%, epirubicin and Adriamycin were similar in their cytotoxicities, although epirubicin was more potent against every line except an Adriamycin-resistant subline. Combinations of the two drugs with a non-cytotoxic concentration (1 microgram/ml) of lonidamine were tested using the Adriamycin-resistant subline MGH-U1R and its sensitive parental line MGH-U1. The addition of lonidamine caused a two-fold increase in the sensitivity of the resistant subline to both drugs, while having no effect on the sensitivity of the parental line. The data indicate that this combination might be of value in anthracycline-resistant disease.

"Urological cold shower"--a novel treatment for intraoperative erection.

Intraoperative penile tumescence during endoscopic surgery is a troublesome complication and a challenge to the urologist. We describe a novel, convenient, safe, and readily available technique. We used an intracavernosal injection of epinephrine using a standard dental syringe and a cartridge of lidocaine 2% and epinephrine 1:80,000 to induce detumescence reliably.