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PURPOSE Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST) assessed whether magnetic resonance images (MRIs) or a reduced scan schedule could be used without an unacceptable increase in advanced relapses. METHODS A phase III, noninferiority, factorial trial. Eligible participants had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Random assignment was to seven CTs (6, 12, 18, 24, 36, 48, and 60 months); seven MRIs (same schedule); three CTs (6, 18, and 36 months); or three MRIs. The primary outcome was 6-year incidence of Royal Marsden Hospital stage ≥ IIC relapse (> 5 cm), aiming to exclude increases ≥ 5.7% (from 5.7% to 11.4%) with MRI ( v CT) or three scans ( v 7); target N = 660, all contributing to both comparisons. Secondary outcomes include relapse ≥ 3 cm, disease-free survival, and overall survival. Intention-to-treat and per-protocol analyses were performed. RESULTS Six hundred sixty-nine patients enrolled (35 UK centers, 2008-2014); mean tumor size was 2.9 cm, and 358 (54%) were low risk (< 4 cm, no rete testis invasion). With a median follow-up of 72 months, 82 (12%) relapsed. Stage ≥ IIC relapse was rare (10 events). Although statistically noninferior, more events occurred with three scans (nine, 2.8%) versus seven scans (one, 0.3%): 2.5% absolute increase, 90% CI (1.0 to 4.1). Only 4/9 could have potentially been detected earlier with seven scans. Noninferiority of MRI versus CT was also shown; fewer events occurred with MRI (two [0.6%] v eight [2.6%]), 1.9% decrease (–3.5 to –0.3). Per-protocol analyses confirmed noninferiority. Five-year survival was 99%, with no tumor-related deaths. CONCLUSION Surveillance is a safe management approach—advanced relapse is rare, salvage treatment successful, and outcomes excellent, regardless of imaging frequency or modality. MRI can be recommended to reduce irradiation; and no adverse impact on long-term outcomes was seen with a reduced schedule.

1. The effect of addition of guar gum (5 and 10 g/l) to a radiolabelled, homogenized, baked-bean test meal on the distribution of that meal in the gastrointestinal tract was investigated in groups of male rats killed at 25, 50, 100, 200, 300 and 400 min after gavage.2. Addition of 5 and 10 g guar gum/l significantly increased the proportion of the meal remaining in the stomach at 25 and 50 min after gavage (P<0·01).3. The heads of the control meal and meals containing guar gum reached the distal small intestine within 25 min after gavage but radioactivity was not observed in the caecum until 100 min after administration of each of the meals. Addition of guar gum (5 and 10 g/l) delayed caecal filling even though the head of each meal reached the caecum at the same time after gavage.4. The geometric centres of guar-gum-containing meals were proximal to that of the control meal at all times after gavage.5. The observed delay in the passage of a guar-gum-containing meal through the stomach and small intestine is probably due to the viscous nature of the meal resisting the propulsive and mixing effects of the gastrointestinal contractions, thereby reducing access of the glucose to the absorptive epithelium. This could contribute to the observed reductions in postprandial glycaemia seen in previous studies after incorporating guar gum into a meal.

Background:The influence of EGFR pathway mutations on cetuximab-containing rectal cancer preoperative chemoradiation (CRT) is uncertain.Methods:In a prospective phase II trial (EXCITE), patients with magnetic resonance imaging (MRI)-defined non-metastatic rectal adenocarinoma threatening/involving the surgical resection plane received pelvic radiotherapy with concurrent capecitabine, irinotecan and cetuximab. Resection was recommended 8 weeks later. The primary endpoint was histopathologically clear (R0) resection margin. Pre-planned retrospective DNA pyrosequencing (PS) and next generation sequencing (NGS) of KRAS, NRAS, PIK3CA and BRAF was performed on the pre-treatment biopsy and resected specimen.Results:Eighty-two patients were recruited and 76 underwent surgery, with R0 resection in 67 (82%, 90%CI: 73–88%) (four patients with clinical complete response declined surgery). Twenty–four patients (30%) had an excellent clinical or pathological response (ECPR). Using NGS 24 (46%) of 52 matched biopsies/resections were discrepant: ten patients (19%) gained 13 new resection mutations compared to biopsy (12 KRAS, one PIK3CA) and 18 (35%) lost 22 mutations (15 KRAS, 7 PIK3CA). Tumours only ever testing RAS wild-type had significantly greater ECPR than tumours with either biopsy or resection RAS mutations (14/29 [48%] vs 10/51 [20%], P=0.008), with a trend towards increased overall survival (HR 0.23, 95% CI 0.05–1.03, P=0.055).Conclusions:This regimen was feasible and the primary study endpoint was met. For the first time using pre-operative rectal CRT, emergence of clinically important new resection mutations is described, likely reflecting intratumoural heterogeneity manifesting either as treatment-driven selective clonal expansion or a geographical biopsy sampling miss.

ImplicationsOestrogens in men are derived from the aromatisation of androgens therefore most androgen suppression strategies used to treat prostate cancer, such as LHRHa, cause a dual set of toxicities related to both androgen and oestrogen depletion. Using tE2 to produce castrate levels of testosterone in men with prostate cancer mitigates the side effects of LHRHa caused by oestrogen depletion (e.g. hot flushes, osteoporosis and adverse metabolic profiles), as well as avoiding the cardiovascular toxicity seen with oral oestrogen.Oestrogens administered transdermally should be considered for androgen suppression in the management of prostate cancer.