Sophie Dorothea Fosså

Purpose: To explore whether prostatectomized men report improved post-operative erectile function and urinary control dependent on the application of intra-operative frozen section examination (NeuroSAFE) during nerve-sparing radical prostatectomies (NS-RPs). Methods: Pre- and post-RP responses to the sexual domain and the urinary incontinence subscale of EPIC-26 were analyzed in 95 and 312 men from a NeuroSAFEGroup (Martini-Klinik, Hamburg, Germany) and a Non-NeuroSAFE Group (Oslo University Hospital, Norway), respectively, undergoing NS-RPs for ≤ cT2 prostate cancer. All patients had intra-prostatic tumors as evaluated by Digital Rectal Examination. Statistical significance in bivariate and multi-variable analyses: p < 0.05. Results: With similar oncological outcomes and not associated with the performance of bilateral or unilateral NS-RP within each group patients from the NeuroSAFE Group had better sexuality outcomes than those from the NonNeuroSAFE Group (p < 0.01). Age and pre-RP sexual function represented significant co-variables. In pre-RP potent men, erectile function was preserved in 74% of men in the NeuroSAFE Group and in 46% in those from the NonNeuroSAFE Group (p < 0.01). Any superior continence-saving effect of NeuroSAFE was limited. The non-randomized small-sized observational study design represents the observations’ main limitation. Conclusions: Our study indicates that NeuroSAFE contributes to preservation of post-RP erectile function. If confirmed in a randomized trial the NeuroSAFE should be applied in patients undergoing NS-RP for maximal preservation of post-RP sexual function.

With the favorable trend regarding survival of cancer in the Western world, there is an increasing focus among patients, clinicians, researchers, and politicians regarding cancer survivors’ health and well-being. The number of survivors grows rapidly, and more than 3% of the adult populations in Western countries have survived cancer for 5 years or more. Cancer survivors are at increased risk for a variety of late effects after treatment, some life-threatening such as secondary cancer and cardiac diseases, while others mainly have negative impact on daily functioning and health-related quality of life (HRQOL). The latter factors include fatigue, anxiety disorders, sexual problems, insomnia, and reduced work ability, while depression does not seem to be more common among survivors than in the general population. Life style factors are highly relevant for cancer survivors concerning risk of relapse and somatic comorbidity. The field of cancer survivorship research has grown rapidly. How to best integrate the knowledge of the field into clinical practice with adequate follow-up of cancer survivors at risk for developing late effects, is still an unresolved question, although several models are under consideration.

10075 Background: TCS are an important group in which to characterize late effects of cancer and its therapy given their young age at diagnosis and high cure rate. We comprehensively evaluated CBM and identified associated clinical, sociodemographic, and behavioral risk factors among TCS given cisplatin based chemotherapy in a multicenter study. Methods: TCS completed a comprehensive health questionnaire. Responses were grouped into 22 adverse health outcomes (AHO) and graded by severity. A CBM score was calculated based on AHO number and severity, following Geenen et al (JAMA 2007). Multivariable ordinal logistic regression examined the association of clinical, sociodemographic, and behavioral factors with CBM. Variable-based hierarchical clustering identified individual AHOs that co-occurred. Results: Among 1,215 TCS (median age at evaluation 38 y, range 19-68 y; time since chemotherapy 4.6 y), over 20% had a CBM score of high (17%), very high (4%) or severe (0.4%). Most TCS, however, had CBM scores of low (37%), medium (28%), very low (9%) or none (5%). In a multivariable model controlling for time since chemotherapy, older attained age (OR 1.2; 95% CI 1.1 - 1.3), being widowed/divorced/separated (OR 1.8; 95% CI 1.1 - 3.1), having less than college-level education (OR 1.7; 95% CI 1.3 - 2.2), being retired/on disability (OR 2.5; 95% CI 1.2 - 5.3), and receipt of 4 cycles of BEP vs. 4 cycles of EP or 3 cycles of BEP (OR 1.3; 95% CI 1.01 - 1.8) were associated with increased odds of a worse CBM score; vigorous exercise (OR 0.7; 95% CI 0.5 - 0.9) and non-white race (OR 0.6; 95% CI 0.4 - 0.9) were associated with decreased odds. A separate cluster analysis revealed five groups of AHOs: those known to be cisplatin-related (e.g. neuropathy, ototoxicity); metabolic abnormalities (e.g. hypercholesterolemia, diabetes); vascular damage (e.g. stroke); testicular cancer-related (e.g. hypogonadism); and other (e.g. thyroid disease). Conclusions: TCS with factors associated with worse CBM may be candidates for closer monitoring. If confirmed, our cluster analysis showing that groups of conditions tend to co-occur in TCS could provide guidance for survivorship care plans.

E18162 Background: RP is an adverse drug reaction characterized by reduced blood flow to the extremities causing pain and sensations of cold. Few studies have examined the genetic basis for RP, although family studies suggest a heritable component to primary RP. Methods: Eligible testicular cancer survivors (TCS) were < 55 y at diagnosis, treated with first line cisplatin-based chemotherapy, and completed questionnaires. Genotyping with standard quality control and imputation were performed. A case-control RP phenotype was derived from patient-reported outcomes and associations were computed by logistic regression. GWAS used cumulative bleomycin dose and 10 genetic principal components as covariates. Gene set enrichment analysis (GSEA) utilized genes ranked by the most significant GWAS SNP in/within 20 kilobases. A polygenic risk score for CVD derived from four prior independent GWAS (Khera et al. NEJM 2016) was assessed for association with RP. Results: Of 749 patients (median age 38 y, median time since chemotherapy 5 y), 38% reported RP. Bleomycin dose was the most significant predictor of RP (OR_{100 mg/m}² = 1.25, p < 0.0001). Number of years smoking also correlated with RP (OR_year = 1.05, p = 0.002). Age and hypertension showed no significant correlation with RP. GSEA revealed several significant pathways (FDR q < 0.1), including “ cellular response to VEGF stimulus” (q = 0.05) and “ cardiac muscle cell action potential” (q = 0.09). We hypothesized that RP may share genetic architecture with CVD. Deriving a polygenic risk score from genome-wide significant SNPs in prior CVD GWAS (n = 4260-22,389), we showed nearly significant case-control differences in CVD polygenic risk score (two-tailed t-test, p = 0.053). RP frequency significantly increased with polygenic risk score quartile (OR = 1.19, p = 0.008). Conclusions: Over one third of TCS report RP, with greater frequency among bleomycin-treated patients and smokers. Implicated genetic pathways include ones established in CVD. Although shared genetic risk between chemotherapy-induced RP and CVD may be possible, further investigation is required. Primary RP has been inconsistently linked with CVD.

4551 Background: Physical activity (PA) is believed to reduce acute side-effects as deconditioning, fatigue and nausea during chemotherapy and enhance post-treatment physical and psychosocial recovery. The national multicenter randomized TAST-trial (clinicaltrial.gov: NCT02577172) aimed to determine the effect of high-intensity training (HIT) during chemotherapy for testicular cancer (TC) on acute and post-treatment physical- and psychosocial outcomes. Methods: Patients aged 18 – 60 years with newly diagnosed metastatic TC, planned for 3 or 4 cisplatin-based chemotherapy cycles in combination with etoposide (EP) or etoposide plus bleomycin (BEP), were randomized to HIT during 9 or 12 weeks of chemotherapy or to one lifestyle counseling session (LCS) during first cycle. The HIT included two supervised endurance interval sessions per week, of which 10-15 minutes per session at 85 – 95 % of peak heart rate. The intensity, duration and number of the intervals were predetermined, but adjusted in accordance to the patients’ daily condition. Thromboembolic (TE) complications were registered consecutively. Results: Among the first 9 patients randomized to HIT, 33% (3 patients aged 22, 30 and 44 years) developed severe TE complications; 2 cases of pulmonary embolism (respectively at day 9 and 7 of BEP cycle 2) and 1 myocardial infarction (at day 7 of BEP cycle 3). Common for these patients were non-seminoma TC, clinical stage IIA, good prognosis group and no known risk factors for TE events. TE complications were not observed among the 10 patients randomized to the LCS. Conclusions: Since TC patients within good prognosis group are expected to have about 5 % risk of TE complications during or shortly after cisplatin-based chemotherapy, we cannot exclude that the HIT may have contributed to the unexpected high number of TE events. Until possible mechanisms explaining our observations have been explored, we discourage high-intensity endurance training during cisplatin-based chemotherapy for TC. These observations led to closure of the TAST-trial after inclusion of 19 of 94 planned patients. Clinical trial information: NCT02577172.

E16047 Background: 80% of TCS were reported to have a hearing loss based on post-CBCT audiograms (American Speech-Language-Hearing Association (ASHA) definition; Frisina et al, JCO 2016:34) Methods: 46 TCS treated with CBCT 1980-1994 with audiograms (0.25-8 kHz) pre chemotherapy (PRE) and at a survey (SURV) after median 10 years were included (cases). Audiograms at SURV from 46 age-matched TCS without CBCT were included as controls. Linear regression was performed to evaluate predictors for change in hearing threshold level (HTL) from PRE to SURV. Mean HTL for both ears exceeding 20 dB at any frequency 0.25-8 kHz were classified as a hearing loss (ASHA definition). We also applied the WHO definition of hearing loss, present if the average HTL threshold for the four frequencies 0.5, 1, 2 and 4 kHz exceeded 20 dB (M4 definition). At SURV, self-reported hearing loss was assessed by a questionnaire (categorized as “a little”, “quite a bit” and “very much” vs. “not at all”). Results: Age and PRE HTL was associated with change in HTL for most frequencies. Cisplatin dose was significantly associated with change in HTL for the frequencies 2 to 8 kHz, with a gradually greater change in HTL and lower p-value with increasing frequencies. For the 8 kHz frequency, each 100 mg increase in cumulative cisplatin dose was associated with a deterioration of 3.6 dB (p < .001). According to ASHA, the prevalence of a hearing loss among cases was 33% PRE, 70% at SURV, and 65% among controls at SURV (cases vs. controls, p = .66). According to M4, the prevalence of hearing loss among cases was 6.5% PRE, 13% at SURV, and 2.2% among controls at SURV (cases vs. controls, p = 0.05). Overall 29% of cases, and 33% of controls (p = .70) reported some degree of hearing impairment at SURV, of whom only 6.5% of cases reported more than “a little”. Self-reported hearing loss was not associated with hearing loss according to ASHA (p = .20), but was associated with the M4 definition (p = .02). Conclusions: Cisplatin is associated with a moderate hearing loss particularly at higher frequencies. Ageing is important for hearing loss regardless of treatment. The ASHA definition of hearing loss overestimates the hearing problem and should not be used as a clinical tool.

102 Background: Testicular cancer has an excellent prognosis since the introduction of platinum-based CHEM. However, several European studies report an excess of cardiovascular disease (CVD) in TCS. MetS is a cluster of cardiovascular risk factors that doubles CVD risk, with several European series noting a prevalence ranging from 13-39% in TCS. In the first large multi-center North American study of TCS, we examine the prevalence of and potential risk factors for MetS after modern CHEM (NCI R01 CA157823). Methods: Eligible TCS were