Search

5009 Background: Radiotherapy is a common and effective treatment for localised prostate cancer. However, recurrence of cancer can occur in 10-15% of men in the following 5 years. Most patients with recurrence are managed using hormonal therapy with associated systemic side-effects and subsequent development of castrate resistance. Salvage prostatectomy confers a high risk of urine incontinence and rectal injury. Accurately localising and ablating only areas of recurrence within the prostate might be effective with fewer side-effects. The FOcal RECurrent Assessment and Salvage Treatment (FORECAST) trial assessed this diagnostic and treatment pathway for men with radiorecurrent cancer (NCT01883128). Methods: We first compared the accuracy of multi-parametric MRI (mp-MRI) and MRI-targeted biopsy in identifying areas of recurrent cancer to a transperineal template prostate mapping (TTPM) biopsy (Apr/2014-Jan/2018) in 181 patients from 6 UK centres. We then assessed the functional and cancer control outcomes of focally ablating areas of intraprostatic recurrence in 93 patients with localised or metastatic cancer (using cryotherapy or HIFU). Primary outcomes were sensitivity of mpMRI and MRI-targeted biopsies and urinary continence after focal ablation. A key secondary outcome was progression free survival (PFS) defined as no new metastases or hormone use (localised group only), or chemotherapy or further local treatment. Results: Of 181 men with suspicion of recurrence following radiotherapy, re-staging whole-body imaging (Choline PET and Bone Scan) showed localised disease in 128 (71%), nodal disease only in 13 (7%) and 38 (21%) metastatic. The sensitivity of MRI-targeted biopsy was 92% (95%CI 83-97%). Specificity, and positive and negative predictive values, were 75% (95%CI 45-92%), 94% (95%CI 86-98%) and 65% (95%CI 38-86%). 4/72 (6%) cancers were missed on TTPM biopsies alone and 6/72 (8%) were missed on MRI-targeted biopsies alone. Overall sensitivity of mpMRI was 81% (95%CI 73-88%) using Likert score 4-5 to denote a positive test. Specificity, and positive and negative predictive values, were 88% (95%CI 73-98%), 96% (95%CI 90-99%) and 57% (95%CI 42-70%). In the 93 men undergoing focal ablation, urinary continence was preserved in 78/93 (84%); 5/93 (5%) had a CTCAE grade 3+ adverse events. There were no rectal injuries. With a median follow-up of 27.8 [SD 1.3] months, PFS was 66% [54-75] at 24-months. Metastases-free survival in the 73 men with localised disease was 80% [95%CI 68–88] at 24-months. There were no cancer specific deaths. Conclusions: Prostate mpMRI and MRI-targeted biopsies can accurately detect and localise recurrent prostate cancer following radiotherapy. Focal ablation to areas of intra-prostatic recurrence preserves continence in the majority of men with good cancer control. Clinical trial information: NCT01883128.

503 Background: Level 1 evidence exists for the use of both neoadjuvant chemotherapy (NAC) and concomitant radiosensitization (CRS) to improve outcomes in patients receiving radical radiotherapy (RT) for muscle invasive bladder cancer, but uptake has been patchy. We report here the current patterns of usage in an ongoing trial of adaptive radiotherapy. Methods: RAIDER is an international randomized phase II trial recruiting patients with unifocal T2-T4a urothelial carcinoma of the bladder suitable for RT (ISCRTN:26779187). Patients are randomized in a 1:1:2 ratio to one of 3 arms: Standard whole bladder RT (control); Standard dose adaptive tumour focused RT; Dose escalated (DE) adaptive tumour boost RT. Standard dose patients are treated to either 64Gy/32f or 55Gy/20f and DE patients to 70Gy in 32f or 60Gy in 20f. Patients are encouraged to receive NAC and CRS. The primary endpoint is the rate of late toxicity 6-18 months post treatment in arm 3, with secondary endpoints of patient reported and disease related outcomes. Results: To August 2019, 285 patients had been recruited. Median age is 72 years (IQR 67-79). Stage of disease is T2 79%, T3 19%, T4 2%; 19% have hydronephrosis. Patients receiving NAC were more likely to be PS 0 at trial entry (70% v 45%). Variation in frequency of CRS use is seen across sites, with some offering to >90% of participants and some

131 Background: In primary treatment of localised prostate cancer, minimally invasive ablative therapies such as HIFU aim to achieve cancer control whilst offering a potentially favourable toxicity profile. At 5 years median follow up, 12% of patients treated with focal HIFU require salvage therapy. PROMS using Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC‐CP) provide a validated and clinically relevant tool to assess and quantify side effects from pelvic radiotherapy. There is limited data on late toxicity using PROMs with salvage radiotherapy in this setting. Methods: Retrospective analysis from prospectively collected data of 28 patients who received salvage radiotherapy at our institution 2010-2018 was performed. Late bowel and urinary toxicity measured by EPIC-CP is reported. Results: Gleason score at diagnosis: 3+3 4/28; 3+4 22/28; 4+3 2/28. HIFU treatment received: focal: 9/28; whole gland: 6/28; focal and redo focal: 7/28; focal and redo whole gland: 1/28; whole gland and redo: 5/28. All patients had mpMRI and biopsy proven recurrence with median PSA 6.6 ng/ml (0.57- 30.89). Median age at radiation was 67 years (55-80). Patients received 74 Gy to the prostate and 4 patients received additional pelvic lymph node irradiation. Three men received conformal radiotherapy (multiphase technique) and 25 arcing intensity modulated radiotherapy with hormone therapy as per risk stratification. Cumulative incidence of toxicity is reported at median follow-up of 43 months (7-99). Overall urinary function: no problem 8/28; very small problem 4/28; small problem 7/28; moderate problem 5/28; big problem 4/28 Urinary Incontinence Symptom Score: 2.5/12 (0-12) Urinary Irritation /Obstructive Symptom Score: 3.1/12 (0-12) Bowel Symptom Score: 3.5/12 (0-11) Biochemical relapse has occurred in 2/28 patients. Conclusions: Functional and oncological outcomes for a greater number of patients treated with minimally invasive ablative therapies followed by salvage radiation are required, however this data suggests radiation is a well-tolerated and effective salvage option following primary HIFU.

547 Background: Platinum-based combination chemotherapy regimens are used in the treatment of carcinoma of the penis, but toxicity limits their value for patients with metastatic disease. This trial aims to define both the toxicity and the rate of disease control for the non-platinum cytotoxic agent Vinflunine. Methods: A phase II single-arm trial was designed to demonstrate a clinical benefit rate of at least 40% and to exclude a rate of less than 15% (p0 = 0.15, p1 = 0.40, α = 0.05, β = 0.80, Fleming-A’hern exact design). 22 evaluable patients were required. Key eligibility criteria included measurable, histologically-proven squamous cell carcinoma of the penis staged as M1; or M0, Tx, N3; or M0, Tx, N2 and deemed inoperable by multidisciplinary team; or M0, T4 any N. Patients were required to have ECOG performance status of 0, 1 or 2 and adequate hepatic and renal function. Treatment comprised four 21-day cycles of vinflunine (320mg/m2) with RECIST v1.1 restaging following cycle 4 (response primary endpoint). Patients deemed to be benefitting from treatment were permitted to continue vinflunine at the discretion of the treating clinician until progression or unacceptable toxicity. Results: 25 patients were recruited from 8 UK centres between June 2014 and May 2017. Median age was 68 years; 19 patients had metastatic (M1) disease. All patients have completed trial treatment and primary endpoint assessment. Data cleaning for the primary analysis is currently in progress, with the snapshot for the primary analysis due in October 2017 and primary analysis to be presented to the trial oversight committees in November 2017. Conclusions: It is hoped that single-agent vinflunine will be associated with a favourable toxicity profile combined with meaningful clinical responses. The results will be available for presentation at the meeting. Clinical trial information: NCT02057913.

425 Background: Squamous cell carcinoma (SCC) of the posterior urethra is rare and is associated with sexually transmitted infections, urethritis, chronic strictures or urethral surgery. Unlike anterior urethral SCC, the presentation of posterior urethral SCC is often late and there are currently no standardised treatment protocols. We present our series of posterior urethral SCC treated by radical surgery and bladder preservation by performing a pan-urethrectomy, radical prostatectomy with a bladder neck closure and chemoradiotherapy. Methods: We retrospectively collected data from patients diagnosed with posterior urethral SCC from a penile cancer database. Data including patient age, histological subtypes, surgical management, post-operative complications, chemo-radiotherapy and survival rates were recorded. Results: A total of 10 cases with histologically proven posterior urethral SCC were treated in a single centre. Median follow-up was 19 months (SD±10 months). Mean age at presentation was 49 years (SD±6.44) and usual type SCC (80%) was the most prevalent histological subtype followed by NOS and condylomatous SCC. The majority of cases were poorly differentiated SCC (70%), stage ≥ T3 and required radical surgery with total urethrectomy and radical prostatectomy. Complications included post-operative ileus (30%), wound infection (20%), sepsis (10%), perioperative transfusion was required in one patient. Lymphovascular invasion was present in 90% of cases and local recurrence occurred in 60% of patients. Only one patient was suitable for neo-adjuvant chemo-radiotherapy (cisplatin/5-FU) and a further 5 required adjuvant chemoradiotherapy following surgery. 60% of patients developed metastatic disease and 60% died with a median survival of 9.6 months (SD±5.3) from diagnosis to death. Conclusions: Posterior urethral SCC is rare and the late presentation means that neoadjuvant chemoradiotherapy is often not possible. Radical surgery requires a pan-urethrectomy and urinary diversion. Despite adjuvant chemoradiotherapy, posterior urethral SCC is associated with significant mortality with a median survivial of less than one year.

283 Background: Muscle invasive bladder cancer (MIBC) incidence increases with age, with many patients (pts) unfit for radical therapy. We aimed to demonstrate feasibility of delivery & acceptable rates of hypofractionated RT toxicity using image guided adaptive techniques for these pts in a multicentre trial. Methods: Pts with T2-T4aN0M0 MIBC had 36 Gray (Gy) in 6 fractions (fr) over 6 weeks & were randomised (1:1) to standard (SP) or adaptive planning (AP). For AP 3 RT plans (small, medium, large) were generated with preRT cone beam (CB) CT used to select best fitting ‘plan of the day’ at each fr. A QA programme aided standardised CBCT image interpretation. The SP group had RT with 1 plan. The aim was to exclude ≥30% grade ≥3 (≥G3) acute (to 3 months (m)) non-genitourinary (GU) toxicity for AP in pts with no MIBC death by 3m (p0=0.7 p1=0.9 α=0.05 β=0.2). Secondary endpoints included 36Gy/6fr acute toxicity in pts who had ≥1 RT fr & proportion of AP fr using small/large plan. Adverse events (AEs) were assessed (CTCAE v4) weekly on RT, 4 weeks & 3m post RT. Blind independent review assessed relatedness of non-GU AEs to RT. Results: Between Apr 2014 & Aug 2016 65 pts were randomised (SP (n=32) AP (n=33)) from 12 UK sites. Median age was 85yrs; 68% male; 92% transitional cell MIBC; 99% grade 3; 25% clinical stage T3 & 6% T4. 58 pts are evaluable to date, ≥G3 acute non-GU adverse reactions (AR) were reported in 2/30 (7%; 90% CI: 1%–20%) AP (G3 hyperkalemia & hyponatremia; G3 diarrhea & dehydration) & 3/28 (11%; 90% CI: 3% –25%) SP pts (G3 fatigue; G3 hyperkalemia, weight loss & anorexia; G3 diarrhoea). 24/65 (37%; 90% CI: 27%-48%) pts who had ≥1 RT fr had ≥G3 acute AEs including G4 hyponatremia (2 AP pts), G5 pneumonia (1 SP, 1 AP), G5 sepsis (1 AP) & G5 renal failure (1 SP) (all G4/5 unrelated to RT). 7/65 pts received 25% fr adapted has potential for benefit. Comparative randomised studies are needed to quantify benefits of AP over SP. Clinical trial information: 18815596.

e16018Background: UK guidelines for treatment of bladder cancer recommend Gemcitabine/Cisplatin (GC) or MVAC (Methotrexate, Vinblastine, Doxorubicin and Cisplatin). Outcomes are similar but reporte...

5600 Background: CTCs are prognostic and predictive markers in many solid tumours. There are no validated biomarkers to assess treatment (tx) response or molecular therapies in aEC. We conducted a ...