The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy: Involvement of Single Versus Multiple Sextant Sites.

CONTEXT.­: Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. OBJECTIVE.­: To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. DESIGN.­: We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. RESULTS.­: PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1-3), pT (GG1-2/GG1-3/GG2/GG3), surgical margin status (GG1-3/GG3/GG5), or tumor volume (GG1-2/GG1-3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1-2 versus 3-6/1-3 versus 4-6/1-4 versus 5-6), RP GG (1-3 versus 4-6/1-4 versus 5-6), pT (1-2 versus 3-6/1-3 versus 4-6), pN (1-3 versus 4-6), or tumor volume (1-2 versus 3-6/1-4 versus 5-6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1-2/GG1-3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). CONCLUSIONS.­: Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1-3 cancer.

Limited Adenocarcinoma of the Prostate on Needle Core Biopsy.

CONTEXT.­: Grading small foci of prostate cancer on a needle biopsy is often difficult, yet the clinical significance of accurate grading remains uncertain. OBJECTIVE.­: To assess if grading of limited adenocarcinoma on prostate biopsy specimen is critical. DESIGN.­: We studied 295 consecutive patients undergoing extended-sextant biopsy with only 1-core involvement of adenocarcinoma, followed by radical prostatectomy. RESULTS.­: The linear tumor lengths on these biopsy specimens were: less than 1 mm (n = 114); 1 mm or more or less than 2 mm (n = 82); 2 mm or more or less than 3 mm (n = 35); and 3 mm or more (n = 64). Longer length was strongly associated with higher Grade Group (GG) on biopsy or prostatectomy specimen, higher risk of extraprostatic extension/seminal vesicle invasion and positive surgical margin, and larger estimated tumor volume. When cases were compared based on biopsy specimen GG, higher grade was strongly associated with higher prostatectomy specimen GG, higher incidence of pT3/pT3b disease, and larger tumor volume. Outcome analysis further showed significantly higher risks for biochemical recurrence after radical prostatectomy in patients with 1 mm or more, 2 mm or more, 3 mm or more, GG2-4, GG3-4, GG4, less than 1 mm/GG2-4, less than 1 mm/GG3-4, less than 2 mm/GG3-4, 3 mm or more/GG2-4, or 3 mm or more/GG3-4 tumor on biopsy specimens, compared with respective control subgroups. In particular, 3 mm or more, GG3, and GG4 on biopsy specimens showed significance as independent prognosticators by multivariate analysis. Meanwhile, there were no significant differences in the rate of upgrading or downgrading after radical prostatectomy among those subgrouped by biopsy specimen tumor length (eg, <1 mm [44.7%] versus ≥1/<2 mm [41.5%] versus ≥2/<3 mm [45.7%] versus ≥3 mm [46.9%]). CONCLUSIONS.­: These results indicate that pathologists still need to make maximum efforts to grade relatively small prostate cancer on biopsy specimens.

The Clinical Impact of pT3a Lesions in Patients With pT3b Prostate Cancer Undergoing Radical Prostatectomy.

CONTEXT.­: Seminal vesicle invasion (SVI) by prostate cancer (pT3b disease) has been considered as a key prognostic factor. OBJECTIVE.­: To assess the clinical impact of T3a lesions (ie, extraprostatic extension other than bladder neck invasion [BNI] or SVI [EPE], microscopic bladder neck invasion [mBNI]) in pT3b disease. DESIGN.­: We compared radical prostatectomy findings and long-term oncologic outcomes in 248 patients with pT3b disease, with versus without EPE/mBNI. RESULTS.­: Extraprostatic extension/mBNI was found in 219 (88.3%)/48 (19.4%) cases, respectively. Extraprostatic extension was significantly associated with higher preoperative prostate-specific antigen (PSA) level, higher rates of positive surgical margin (pSM) and lymphovascular invasion (LVI), and larger tumor volume. Similarly, mBNI was significantly associated with higher PSA level, higher rates of Grade Group(s) 4-5 or 5, pSM, LVI, and pN1, and larger tumor volume. Significant differences in all of these clinicopathologic features (except lymph node metastasis) between EPE-/mBNI+ or EPE+/mBNI- and EPE+/mBNI+ cases were also observed. Outcome analysis revealed that patients with EPE (P < .001) or mBNI (P < .001) had a significantly higher risk of disease progression than respective controls. Notably, there were significant differences in progression-free survival between EPE-/mBNI+ or EPE+/mBNI- cases and EPE-/mBNI- (P = .001) or EPE+/mBNI+ (P < .001) cases. In multivariate analysis, EPE (hazard ratio [HR] = 6.53, P = .009) and mBNI (HR = 2.33, P = .003), as well as EPE-/mBNI+ or EPE+/mBNI- (HR = 11.7, P = .01) and EPE+/mBNI+ (HR = 25.9, P = .002) versus EPE-/mBNI-, showed significance for progression. CONCLUSIONS.­: From these significant findings, we propose a novel pT3b subclassification: pT3b1 (SVI alone without EPE or mBNI), pT3b2 (SVI with either EPE or mBNI), and pT3b3 (SVI with both EPE and mBNI).

The Clinical Impact of Unilateral Versus Bilateral Invasion Into the Seminal Vesicle in Patients With Prostate Cancer Undergoing Radical Prostatectomy.

CONTEXT.­: Seminal vesicle involvement by prostate cancer has generally been considered as a key prognosticator. OBJECTIVE.­: To assess the clinical significance of unilateral (Uni) versus bilateral (Bil) seminal vesicle invasion (SVI). DESIGN.­: We compared radical prostatectomy findings and long-term oncologic outcomes in 248 patients showing Uni-SVI (n = 139) versus Bil-SVI (n = 109). RESULTS.­: Tumor grade was significantly higher in Bil-SVI cases than in Uni-SVI cases. Additionally, Bil-SVI was significantly associated with a higher incidence of lymphovascular invasion, lymph node metastasis, or positive surgical margin, and larger estimated tumor volume. When the histopathologic features at SVI foci were compared, Grade Group (GG) 3-5/4-5/5 and cribriform morphology were significantly more often seen in Bil-SVI. Outcome analysis revealed that patients with Bil-SVI had a significantly higher risk of disease progression (P < .001) than patients with Uni-SVI. Significantly worse progression-free survival in patients with Bil-SVI was also observed in all subgroups examined, including those with no immediate adjuvant therapy (IAT) (n = 139; P = .01), IAT (n = 109; P = .001), pN0 disease (n = 153; P = .002), or pN1 disease (n = 93; P = .006). In multivariate analysis, Bil-SVI (versus Uni-SVI) showed significance for progression in the entire (hazard ratio [HR] = 1.83, P = .01), IAT (HR = 2.90, P = .006), and pN0 (HR = 2.05, P = .01) cohorts. Meanwhile, tumor grade at SVI (eg, GG4, GG5), as an independent predictor, was significantly associated with patient outcomes. CONCLUSIONS.­: Bil-SVI was found to be strongly associated with worse histopathologic features on radical prostatectomy and poorer prognosis. Pathologists may thus need to report Uni-SVI versus Bil-SVI, along with other histopathologic findings, such as Gleason score, at SVI in prostatectomy specimens.

Application of IRIS Three-Dimensional Anatomical Models As Preoperative Surgical Planning Tools in the Management of Localized Renal Masses.

Introduction: The use of volume-rendered images is gaining popularity in the surgical planning for complex procedures. IRIS™ is an interactive software that delivers three-dimensional (3D) virtual anatomical models. We aimed to evaluate the preoperative clinical utility of IRIS for patients with ≤T2 localized renal tumors who underwent either partial nephrectomy (PN) or radical nephrectomy (RN). Patients and Methods: Six urologists (four faculty and two trainees) reviewed CT scans of 40 cases over 2 study phases, using conventional two-dimensional (2D) CT alone (Phase-I), followed by the CT + IRIS 3D model (Phase-II). After each review, surgeons reported their decision on performing a PN or an RN and rated (Likert scale) their confidence in completing the procedure as well as how the imaging modality influenced specific procedural decisions. Modifications to the choice of procedure and confidence in decisions between both phases were compared for the same surgeon. Concordance between surgeons was also evaluated. Results: A total of 462 reviews were included in the analysis (231 in each phase). In 64% (95% CI: 58-70%) of reviews, surgeons reported that IRIS achieved a better spatial orientation, understanding of the anatomy, and offered additional information compared with 2D CT alone. IRIS impacted the planned procedure in 20% of the reviews (3.5% changed decision from PN to RN and 16.5% changed from RN to PN). In the remaining 80% of reviews, surgeons' confidence increased from 78% (95% CI: 72-84%) with 2D CT, to 87% (95% CI: 82-92%) with IRIS (p = 0.02); this confidence change was more pronounced in cases with a high RENAL score (p = 0.009). In 99% of the reviews, surgeons rated that the IRIS accurately represented the anatomical details of all kidney components. Conclusion: Application of IRIS 3D models could influence the surgical decision-making process and improve surgeons' confidence, especially for robot-assisted management of complex renal tumors.

Robot-assisted Synchronous Bilateral Nephrectomy for Autosomal Dominant Polycystic Kidney Disease: A Stepwise Description of Technique.

OBJECTIVE: To describe our technique of robot-assisted synchronous bilateral nephrectomy (RASBN) for autosomal dominant polycystic kidney disease (ADPKD). METHODS: Given prior abdominal surgery/transplant in most patients, we prefer an open cut-down access to place a 12 mm port 10 cm infraumbilically. Four (8 mm) robotic ports are then placed under vision in a fan distribution along the umbilical level. The operating table is placed in reverse Trendelenburg and tilted opposite to the targeted side. Provided there are no concerns for malignancy, some cysts encountered in large kidneys (>2.5 L) may require puncture, to facilitate access and mobilization. The resected kidney is placed in a large bag and tucked in the pelvis. A similar procedure is carried out on the contralateral side after redocking the robot and tilting the table in the opposite direction. The specimen bags are extracted by elongating the lower midline 12 mm port site. RESULTS: Seven cases of RASBN performed for ADPKD were identified (December 2015 to December 2018). Median (interquartile range, IQR) values for patient demographics were: Age = 59 years (47-63), body mass index = 29 (26-32), and American Society of Anaesthesiology grade = 3. Three patients had prior deceased- and 4 had prior living- donor transplants. Indication for nephrectomy were: pain (5), hemorrhage into cysts (3), and renal masses (2). Perioperative outcomes were: operating room time = 388 minutes, estimated blood loss = 200 mL, hemoglobin change = 1.3 g/dL, transfusion = 0, length of hospital stay = 3 days, Grade I Clavien-Dindo complications = 2 cases. All patients were alive at a median follow-up of 3.8 years. CONCLUSION: RASBN is safe and effective in ADPKD even in the context of prior renal transplant patients with attendant comorbidities.

Oncological and functional outcomes in patients over 70 years of age treated with robotic radical prostatectomy: a propensity-matched analysis.

PURPOSE: The aim of this study was to report on the safety (complications) and efficacy (oncological and functional outcomes) of robot-assisted radical prostatectomy (RARP), performed at our institution, in patients aged over 70. PATIENTS AND METHODS: Review of our prospectively collected database [Cancer Information Systems (CAISIS)] identified two hundred and fifteen (215) patients, aged > 70, who underwent RARP for localized prostate cancer between July 2003 and August 2017. A propensity score-matched analysis, with multiple covariates, was performed to stratify the patients into Age ≤ 70 and Age > 70 comparison groups. RESULTS: Apart from Age (mean ± SD years: 73.5 ± 2.1 vs 59.5 ± 5.9, p < 0.0001) and nerve-sparing status, the two groups were evenly matched for all covariates (p values > 0.05). Median follow-up was 10.6 years. There were no 90-day mortalities in either group. Minor complications (Clavien ≤ 2) were more common in the Age > 70 group (p = 0.0002). Operating room time (p = 0.83), length of hospital stay (p = 0.06) and catheterization duration (p = 0.13) were similar. On final pathology, a higher pT stage (p < 0.0001) and pN1 (p = 0.003) were observed in the Age > 70 group. However, this did not translate adversely into higher rates of positive surgical margin (p = 0.41) or biochemical relapse (p = 0.72). Allowing for the follow-up duration (median 10.6 years), cancer-specific survival was marginally significant (p = 0.05) with an observed lower rate in the Age > 70 group. In terms of functional outcomes, post-operative erectile dysfunction and pad-free continence were significantly better in the younger cohort (p < 0.0001). CONCLUSIONS: Robot-assisted radical prostatectomy should not be denied to those over 70 years solely on the basis of age. Older men need to be counseled about the likelihood of encountering higher-risk features on final pathology and that their functional outcomes may be worse compared to a younger person.

Accelerated Skills Acquisition Protocol (ASAP) in optimizing robotic surgical simulation training: a prospective randomized study.

PURPOSE: To assess the efficacy of an accelerated proficiency-based training protocol in robotic simulation practice in delivering durable proficiency compared to conventional training methods. METHODS: Novice medical students (n = 16) were randomized into either the accelerated skills acquisition protocol (ASAP) or conventional training protocol (CTP). Subjects were trained to proficiency on the da Vinci Skills Simulator (dVSS) by an expert trainer. Differences in the repetitions required to achieve proficiency in two simple and two complex virtual reality (VR) training tasks were assessed as the primary outcome measure. Transfer of the acquired skills to two other non-practiced tasks was assessed immediately and prospectively followed through to 3, 6 and 12 months in the two groups. Retention of the practiced tasks was assessed along the same timeframe. RESULTS: Subjects in the ASAP group acquired proficiency significantly faster in three of the four training tasks: camera control (p = 0.0002), suture sponge (p < 0.0001), ring walk3 (p < 0.0001), and peg board (p = 0.6936). When assessing transfer of skills, there were no significant differences between the two groups: Ring rail 3 (p = 0.6807) and Tubes (p = 0.2240). When assessing retention of skills at 3, 6 and 12 months, for all 6 tasks, no significant differences were seen between the ASAP and CTP groups. CONCLUSION: ASAP is proven to be an efficient approach for delivering proficiency in robotic VR simulation training. The results are durable when compared to conventional simulation training methods. The findings may have significant implications in the design of robotic VR simulation curricula.

Prognostic DNA Methylation Biomarkers in High-risk Non-muscle-invasive Bladder Cancer: A Systematic Review to Identify Loci for Prospective Validation.

CONTEXT: High-risk non-muscle-invasive bladder cancer (HR-NMIBC) represents over 30% of all incident urothelial bladder cancers (BCs); patients are at risk of progression, and 20-30% will die from BC within 5 yr. Current guidelines recommend induction and maintenance of intravesical bacillus Calmette-Guérin (BCG) or upfront radical cystectomy for highest-risk disease, treatments with markedly different morbidity, mortality, and patient burden. There are no validated biomarkers to facilitate such treatment decisions. Alterations in DNA methylation are commonplace in BC; hence, measurable changes in DNA methylation represent an opportunity for the discovery of such biomarkers. OBJECTIVE: To systematically assess the evidence regarding DNA methylation markers as prognosticators for HR-NMIBC. EVIDENCE ACQUISITION: Standard systematic review methods were employed with searches undertaken in MEDLINE, EMBASE, and PubMed up to January 2019. Studies that included patients with HR-NMIBC and investigated the utility of DNA methylation biomarkers as prognostic tools were included. EVIDENCE SYNTHESIS: Of 63 prognostic biomarker studies identified, 21 met the protocol-driven inclusion criteria and were directly relevant to HR-NMIBC patient outcomes: tumour recurrence (TR), tumour progression (TP), disease-specific survival (DSS), and overall survival (OS). These studies described 140 methylation markers; of these, the most promising were cadherin-13 (CDH13; hazard ratios [HRs]: 5.1 for TR, 6.6 for TP, 3.8-8.0 for OS), protocadherins (PCDHs; HRs: 4.7 for TR, 2.5 for TP, 3.0-4.8 for OS), Runt domain transcription factor 3 (RUNX3; HR: 5.1 for TP), Homeobox 9 (HOXA9; HR: 1.9 for TR), Islet-1 (ISL1; HRs: 1.7 for TR, 3.3 for TP), and PAX6 (HR: 2.2 for TR). CONCLUSIONS: This systematic review identifies a number of potentially useful prognostic methylation markers for HR-NMIBC. These loci (CDH13, PCDHs, RUNX3, HOXA9, ISL1, and PAX6) should be validated in prospective studies in order to translate benefit to patients. PATIENT SUMMARY: Early bladder cancer represents a more complex spectrum of disease than can be assessed by conventional methods Emerging studies on molecular markers will improve our understanding of this disease, and may enable more precise and personalised treatment.

Percutaneous Nephrolithotomy and Spina Bifida: Complex Major Stone Surgery?

BACKGROUND: The incidence of spina bifida (SB) is ∼1:1000, and risk of stone disease is substantially raised in SB. This is the unique published study of the outcome of patients with SB undergoing percutaneous nephrolithotomy (PCNL) compared to a neurologically intact historically matched control group at the same institution. PATIENTS AND METHOD: A series of 96 PCNLs in 13 SB and 50 non-SB patients was analyzed. The following measurements were recorded: (1) Comorbidities; (2) Preoperative: (renal function, American Society of Anesthesiologists [ASA] score); (3) Intraoperative: (anesthesia time, number of tracks, stone-free rate); and (4) Postoperative: (sepsis, intensive therapy unit and total length of stay, transfusion rate, stone composition, rate of stone disease-related nephrectomy). RESULTS: Retrograde access to the ureter was impossible in all cases of SB. The median ASA grade (OR 10.5, 95% confidence interval [CI] 2.6-42.7) and operative time (median difference 30 minutes, 95% CI 20-40) were both higher in the SB cohort. Surgeon's estimate of stone-free rate was significantly lower in the SB cohort (46% vs 82%). Intensive care requirement (0.29 days/PCNL vs 0.1 days/PCNL); total hospital stay (7 days vs 4 days); postoperative transfusion rate (11.8% vs 1.6%); and sepsis rate (38% vs 1.6%) were all significantly higher in the SB group. Repeat PCNL and nephrectomy for recurrent stone disease were both significantly increased in SB cohort compared to control group. CONCLUSIONS: PCNL in patients with SB is associated with multiple parameters of poor outcome. Patients with SB should be counseled about increased peri-operative risk and likelihood of stone recurrence. In an era where hospitals are judged according to comparative outcomes, a case may be made for comparing PCNL in this cohort of patients separately because of the significantly increased peri- and postoperative morbidity.

Primary prostate sarcoma: how to manage following diagnosis at transurethral resection.

Primary prostate sarcomas are rare, reportedly comprising just 0.7% of all prostate malignancies. Here, we present the case of a 66-year-old man who was diagnosed with prostate stromal sarcoma after undergoing a routine transurethral resection of prostate for bladder outflow obstruction. Primary prostate sarcoma can be aggressive even when low-grade, with a high risk of local recurrence and, high malignant potential when high-grade. They require aggressive multimodality treatment with surgery, chemotherapy and radiotherapy for durable survival outcomes. They also require close surveillance with long-term follow-up.

Loss of expression of the tumour suppressor gene AIMP3 predicts survival following radiotherapy in muscle-invasive bladder cancer.

The aim of this study was to test the utility of AIMP3, an upstream regulator of DNA damage response following genotoxic stress, as a clinical biomarker in muscle-invasive bladder cancer (MIBC). AIMP3 was identified from a meta-analysis of a global gene-expression dataset. AIMP3 protein expression was determined by immunohistochemistry on a customised bladder cancer tissue-microarray (TMA). The mechanism of gene silencing was probed using methylation-specific PCR. The association between AIMP3 expression, Tp53 transactivity and genomic stability was analysed. In vitro AIMP3 translocation to the nucleus in response to ionising radiation was demonstrated using immunofluorescence. Radiosensitisation effects of siRNA-mediated AIMP3-knockdown were measured using colony forming assays. TMAs derived from patients enrolled in BCON, a Phase III multicentre radiotherapy trial in bladder cancer (ISRCTN45938399) were used to evaluate the association between AIMP3 expression and survival. The prognostic value of AIMP3 expression was determined in a TMA derived from patients treated by radical cystectomy. Loss of AIMP3 expression was frequent in MIBC and associated with impaired Tp53 transactivity and genomic instability. AIMP3-knockdown was associated with an increase in radioresistance. Loss of AIMP3 expression was associated with survival in MIBC patients following radiotherapy (HR = 0.53; 95% CI: 0.36 to 0.78, p = 0.002) but was not prognostic in the cystectomy set. In conclusion, AIMP3 expression is lost in a subset of bladder cancers and is significantly predictive of survival following radiotherapy in MIBC patients.

Long-term outcomes of augmentation ileocystoplasty in patients with spinal cord injury: a minimum of 10 years of follow-up.

OBJECTIVE: To report the long-term outcomes of augmentation ileocystoplasty (AIC) in patients with spinal cord injury (SCI), with a minimum follow-up period of 10 years. PATIENTS AND METHODS: We retrospectively analysed all operations performed by a single surgeon at a specialist spinal unit. Outcomes were measured by comparing preoperative and follow-up videocystometrograms (VCMGs). Complications were identified from case notes and the surgery database. Subjective assessment was through a previously validated questionnaire. RESULTS: The mean (range) follow-up was 14.7 (10.5-20.3) years. There were 19 patients (12 males) with a mean (range) age at time of surgery of 28.9 (12-52) years. The mean (range) period from injury to surgery was 4.5 (0.3-22) years. All had suprasacral injuries. The VCMGs showed a significant improvement in bladder capacity and a decrease in intravesical pressures (P < 0.001). Long-term complications included bladder stones (n= 4); urosepsis (n= 2); vesico-ureteric reflux ([VUR]n= 2), VUR requiring ureteric re-implantation (n= 1); neurogenic detrusor overactivity ([NDO]n= 1); and laparatomy for bowel obstruction (n= 1). Surveillance cystoscopies did not detect any bladder neoplasms. The response rate for the questionnaire survey was 14/17; 13/14 patients were satisfied with the operation such that they would consider it again or recommend it to a friend. No patient reported any significant changes in either bowel habit or sexual function. CONCLUSIONS: We found that AIC has excellent long-term outcomes in the definitive management of refractory NDO in patients with SCI. The complications of AIC appear to be more than counterbalanced by a high level of patient satisfaction with the procedure and by the achievement of the primary aim of ensuring continence and upper tract safety in these patients.

Risk of bladder tumours after childhood cancer: the British Childhood Cancer Survivor Study.

OBJECTIVES: To estimate the risk of a second primary tumour (SPT) of the bladder in a cohort of childhood cancer survivors, investigate factors associated with a bladder SPT developing, and compare the risk observed with that expected from the general population. PATIENTS AND METHODS: The analysis included 17981 individuals diagnosed with childhood cancer, between 1940 and 1991 in Britain, and surviving for ≥5 years. Ascertainment of a bladder SPT was primarily through the National Health Service Central Registers (NHSCR). RESULTS: From the NHSCR, 17 bladder SPTs were ascertained; this corresponded to four times (95% confidence interval 2.5-6.4) the expected number of bladder tumours. Standardized incidence ratios (SIRs) varied significantly (P < 0.05) by first primary tumour (FPT) type, follow-up period, attained age and chemotherapy. The highest SIRs were in those: with heritable retinoblastoma (31.4); treated with chemotherapy (12.0); 0-9 years of follow-up (10.8); and aged 0-19 years (9.3). The absolute excess risk (AER) for a bladder SPT was 3.7 cases/100000 survivors per year. The AER varied significantly by FPT type, follow-up period, attained age and gender. The highest AERs were in those: diagnosed with heritable retinoblastoma (34.0); 20-29 years of follow-up (14.2); aged 40-49 years (13.0); and male (5.8). Using multivariable Cox regression, FPT and chemotherapy were significantly associated with the risk of a bladder SPT developing. By the age of 55 years, 0.4% of survivors developed a bladder SPT. CONCLUSION: Although the absolute risk of a bladder tumour within childhood cancer survivors was low, the risk was four times that expected from the general population. Specific groups, e.g. survivors of heritable retinoblastoma and those treated with chemotherapy, were at the highest risk.