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Cancer treatment during reproductive ages may negatively impact fertility and there is a need of firm knowledge about the prevalence and predictors of fertility-related distress. The aim was to examine fertility-related distress in a population-based sample of young women and men recently treated for cancer and to identify predictors for this outcome. This nationwide cohort study included 1010 individuals (694 women and 316 men), mean age 34.5 ± 4.9 and 32.1 ± 5.5, respectively, diagnosed with breast, cervical, ovarian, testicular cancers, brain tumors or lymphoma at ages 18–39 in Sweden. Participants completed a survey 1.5-year post-diagnosis to assess fertility-related distress (RCAC), emotional distress (HADS) and self-efficacy, as well as sociodemographic and clinical factors and fertility preservation. Logistic regression was used to examine associations between explanatory factors and high fertility-related distress (RCAC subscale mean >4). Many participants (69% of women and 47% of men) had previous children and about half reported a wish for future children. High fertility-related distress was more prevalent among women (54%) than men (27%), and women were more likely than men to report distress concerning all but one RCAC dimension after adjustment for sociodemographic factors. Use of fertility preservation was unevenly distributed (15% of women and 71% of men) and was not associated with decreased fertility-related distress. In multivariable logistic regression models, a wish for future children, being single, not having previous children, symptoms of anxiety and low self-efficacy regarding one's ability to handle threats of infertility were associated with high fertility-related distress. This nationwide study found a high prevalence of fertility-related distress in young women and men recently treated for cancer and identified sociodemographic and psychological predictors. Fertility preservation was not found to act as a buffer against fertility-related distress, indicating the continuous need to identify strategies to alleviate fertility distress following cancer. [ABSTRACT FROM AUTHOR]

Background: Patients with stage II seminoma have traditionally been treated with photons to the retroperitoneal and iliac space, which leads to a substantial dose bath to abdominal and pelvic organs at risk (OAR). As these patients are young and with excellent prognosis, reducing dose to OAR and thereby the risk of secondary cancer is of utmost importance. We compared IMPT to opposing IMRT fields and VMAT, assessing dose to OAR and both overall and organ-specific secondary cancer risk. Material and methods: A comparative treatment planning study was conducted on planning CTscans from ten patients with stage II seminoma, treated with photons to a 'dog-leg' field with doses ranging from 20 to 25Gy and a 10Gy sequential boost to the metastatic lymph node(s). Photon plans were either 3-4 field IMRT (Eclipse) or 1-2 arc VMAT (Pinnacle). Proton plans used robust (5mm; 3.5%) IMPT (Eclipse), multi field optimization with 3 posterior fields supplemented by 2 anterior fields at the level of the iliac vessels. Thirty plans were generated. Mean doses to OARs were compared for IMRT vs IMPT and VMAT vs IMPT. The risk of secondary cancer was calculated according to the model described by Schneider, using excess absolute risk (EAR, per 10,000 persons per year) for body outline, stomach, duodenum, pancreas, bowel, bladder and spinal cord. Results: Mean doses to all OARs were significantly lower with IMPT except similar kidney (IMRT) and spinal cord (VMAT) doses. The relative EAR for body outline was 0.59 for IMPT/IMRT (p<.05) and 0.33 for IMPT/VMAT (p<.05). Organ specific secondary cancer risk was also lower for IMPT except for pancreas and duodenum. Conclusion: Proton therapy reduced radiation dose to OAR compared to both IMRT and VMAT plans, and potentially reduce the risk of secondary cancer both overall and for most OAR. [ABSTRACT FROM AUTHOR]

Testicular cancer survivors (TCS) are at risk of Leydig cell insufficiency, which is a condition characterized by elevated luteinising hormone (LH) in combination with low levels of testosterone. It has been suggested that this condition is associated with impaired metabolic profile and low bone mineral density (BMD). The primary aim of the randomized double-blind trial NCT02991209 was to evaluate metabolic profile after 12-months testosterone replacement therapy (TRT) in TCS with mild Leydig cell insufficiency. Here we present the secondary outcomes of changes in BMD and markers of bone turnover. In total, 69 TCS with mild Leydig cell insufficiency were randomized 1:1 to 12 months TRT (n = 35) (Tostran, gel, 2%, applied transdermally, with a maximum daily dose of 40 mg) or placebo (n = 34). BMD and markers of bone turnover were evaluated at baseline, after 6- and 12-months TRT, and 3-months post-treatment. Linear mixed effects models were used to analyse changes in BMD, N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX). After 12 months treatment, TRT was not associated with a statistically significant difference in BMD compared to placebo; total body BMD: 0.01 g/cm2 (95% confidence interval (CI): −0.01 − 0.02), BMD of the lumbar spine: 0.01 g/cm2, (95% CI: −0.01–0.03), BMD of the left femoral neck: 0.00, (95% CI: −0.01–0.02). TRT was associated with a small but statistically significant increase in P1NP: 11.65 µg/L (95% CI: 3.96, 19.35), while there was no difference in CTX. 12 months of TRT did not change BMD, while there was as small and clinically irrelevant increase in P1NP compared to placebo in TCS with mild Leydig cell insufficiency. The findings need validation in a larger cohort. [ABSTRACT FROM AUTHOR]

Background: Men with testicular cancer receiving platinum-based chemotherapy have an increased risk of thromboembolic events, with incidence rates between 8–24%. A recent trial evaluating the effect of high-intensity interval training (HIIT) prematurely closed as three out of nine participants (33%) in the intervention group developed a thromboembolic event. The purpose of this retrospective cohort study was: 1) (primary) to evaluate the incidence of thromboembolic events in men receiving chemotherapy for testicular cancer who had participated in HIIT during a 6-week exercise program (Body & Cancer) 2) to describe the feasibility of this program. Material and methods: Forty men who had participated in at least one HIIT session from February 2007 to February 2020 were included. Electronic medical records were searched for incident thromboembolic events (arterial and venous) during Body & Cancer and up to one-year post-chemotherapy. Attendance, cardiorespiratory fitness (VO2-peak), and upper and lower extremity muscular strength (1 repetition maximum (RM)) were obtained from the Body & Cancer database. Results: One participant developed a thromboembolic event during Body & Cancer. No participants developed a thromboembolic event in the follow-up period. In all, data represent 160 HIIT sessions with a median attendance of eight sessions [range 1–19]. Statistically significant increases in upper and lower extremity strength were observed (8.6 (4.2 to 13.0) and 26.0 (14.9 to 37.0) kg, respectively). No significant increase in cardiorespiratory fitness was found (0.14 (−0.03 to 0.31) l/min). Conclusion: While conclusions on the safety of HIIT cannot be drawn, data from the present study do not support previous findings cautioning avoidance of HIIT due to a possible added risk of thromboembolic events in men receiving platinum-based chemotherapy for testicular cancer. Considering the potential for positive effects on cardiovascular outcomes associated with HIIT, future studies with robust design should be performed in this population to confirm these observations. [ABSTRACT FROM AUTHOR]

Purpose: In this paper, we present age-standardized cancer incidence and mortality rates in the Faroe Islands. We also compare with the Nordic rates and show incidence rate ratios (IRR) and mortality rate ratios (MRR). Materials and methods: The Faroese cancer registry (FCR) was established in 1994, with incidence available from 1960 and mortality from 1983. The FCR is a part of the NORDCAN collaboration, where the different Nordic countries all report anonymized cancer data by standardized methods, ensuring comparability. Validation efforts revealed that 13% of cases had not been reported to the FCR from 2006 to 2019, emphasizing the need for continued validation efforts of cancer registries. After validation, we submitted the updated cancer cases to NORDCAN and now present this data, taken directly from the NORDCAN website (2019 data). Results: We found that the incidence of the summary group all cancers in the Faroe Islands increased from 1960 to 2019, while cancer mortality decreased from 1983 to 2019. Comparisons with Nordic rates showed significantly lower IRRs for cancer in all cancers, bladder and urinary tract, and skin cancer for both sexes, while IRR was lower for breast cancer in women and prostate cancer in men. Contrary, IRR was higher for rectum and kidney cancer in women and esophagus and testicular cancer in men. There was an increased MRR for cancer in female organs, bladder and urinary tract, and kidney cancer in women, and esophagus and pancreas cancer in men. In contrast, malignant hematopoietic diseases and melanoma in women had a lower MRR. Conclusions: Cancer incidence in the Faroe Islands was lower than in the other Nordic countries. Of particular interest, the incidence of testicular cancer saw a steep increase during the last 20 years, and an investigation into possible causes for this is needed. [ABSTRACT FROM AUTHOR]

Thyroid hypofunction is a late effect observed in several groups of cancer survivors, but has to date not been evaluated in-depth in testicular cancer survivors (TCSs). We investigated the prevalence of thyroid hypofunction in long-term TCSs and compared the findings with those of a comparison group from the general population. Norwegian TCSs diagnosed with unilateral testicular cancer in the period 1980–1994 (N = 1,436) were grouped according to their cancer treatment (Surgery only; Radiotherapy only; Cisplatin-based chemotherapy, eventually combined with radiotherapy). They were invited to participate in three surveys covering up to three decades post-diagnosis. Serum thyrotropin (s-TSH) from samples collected from the last survey were analyzed. S-TSH results were also available from a health survey of the general population performed in a county in mid-Norway (the HUNT3 Survey [comparison group]). Data on the prescription of thyroid hormone replacement therapy (levothyroxine) from the Norwegian Prescription Database were obtained for the TCSs and the comparison group's participants. Thyroid hypofunction was defined as 'untreated' (overt or subclinical) hypothyroidism (with s-TSH ≥3.5 mIU/L and no regular prescription of levothyroxine) or 'treated' hypothyroidism with regular prescription of levothyroxine. Three decades after diagnosis the prevalence of thyroid hypofunction (i.e., both treated and untreated) was 11% in the TCSs and the prevalence ratio was 1.9 indicating an almost doubled prevalence in the TCSs compared to the comparison group (prevalence ratio 1.91, 95% CI [1.54; 2.38]). However, there were no significant differences in the risk of thyroid hypofunction related to the TCSs' treatment modality. TCSs may have an increased prevalence of thyroid hypofunction compared to the general population. Hypothyroidism has negative consequences related both to primary hypogonadism and to cardiovascular disease. As both conditions are overrepresented in TCSs, regular monitoring of thyroid hormones may be advisable. [ABSTRACT FROM AUTHOR]

Infertility is a well-known sequela of cancer treatment. Despite guidelines recommending early discussions about risk of fertility impairment and fertility preservation options, not all patients of reproductive age receive such information. This study aimed to investigate young adult cancer patients' receipt of fertility-related information and use of fertility preservation, and to identify sociodemographic and clinical factors associated with receipt of information. A population-based cross-sectional survey study was conducted with 1010 young adults with cancer in Sweden (response rate 67%). The inclusion criteria were: a previous diagnosis of breast cancer, cervical cancer, ovarian cancer, brain tumor, lymphoma or testicular cancer between 2016 and 2017, at an age between 18 and 39 years. Data were analyzed using logistic regression models. A majority of men (81%) and women (78%) reported having received information about the potential impact of cancer/treatment on their fertility. A higher percentage of men than women reported being informed about fertility preservation (84% men vs. 40% women, p <.001) and using gamete or gonadal cryopreservation (71% men vs. 15% women, p <.001). Patients with brain tumors and patients without a pretreatment desire for children were less likely to report being informed about potential impact on their fertility and about fertility preservation. In addition, being born outside Sweden was negatively associated with reported receipt of information about impact of cancer treatment on fertility. Among women, older age (>35 years), non-heterosexuality and being a parent were additional factors negatively associated with reported receipt of information about fertility preservation. There is room for improvement in the equal provision of information about fertility issues to young adult cancer patients. [ABSTRACT FROM AUTHOR]

Cisplatin-based chemotherapy (CBCT) can cause high-frequency hearing loss, but little is known about the development and clinical relevance of this hearing loss in survivors of adult-onset cancer with very long-term follow-up. This case-control study investigates hearing and speech perception both in quiet and with background noise 30-years after CBCT. One-hundred-and-one patients (Cases) who received CBCT for testicular cancer between 1980 and 1994 were assessed with pure-tone audiometry (.125 − 8 kHz) and speech perception tests including hearing in noise test (HINT). Self-reported hearing and tinnitus was scored by participants. Results were compared with 30 age-matched controls. The median age of Cases and Controls was 60 (46 − 83) and 61 years (51 − 74), respectively. The median observation time for Cases was 30 years (22 − 37). Compared with Controls, Cases had 8 and 19 dB worse age-adjusted high-frequency hearing at 6 and 8 kHz, respectively (p <.05), while thresholds at lower frequencies did not differ. All but four Cases reached 100% speech perception with basic speech audiometry. There was no difference between Cases and Controls in speech perception neither in quiet nor with both speech and background noise from the front, although the within-group variance was greater among Cases. Cases scored slightly worse with speech from front and noise from either side. Self-reported hearing loss (both hearing loss in general and specifically with background noise), and tinnitus were about three times more common among Cases compared with Controls. Cisplatin causes high-frequency hearing loss, but speech perception tests performed both in quiet and in background noise 30 years post-treatment indicate that the clinical relevance is limited for most patients. Few patients develop severe hearing loss that requires rehabilitation but it is important to identify these patients. Self-reported hearing loss and tinnitus were more common among Cases compared with Controls. [ABSTRACT FROM AUTHOR]

Treatment for disseminated testicular cancer increases the risk of secondary malignancy and cardiovascular disease. The risk of developing these serious adverse effects may be positively affected by healthy living. The purpose of this study was to identify health behaviours with possible influence on late effects that could be targets for intervention. In this cross-sectional study, testicular cancer survivors diagnosed in the period 1984–2007 from the Danish Testicular Cancer database completed a questionnaire on health behaviours (2014–2016). We estimated prevalence of smoking, alcohol consumption, sedentary lifestyle and overweight. Prevalence ratios described with 95% confidence intervals of adverse health behaviours were stratified by treatment modalities and compared to a reference population by means of logistic regression with adjustment for sociodemographic confounders. In total, 2395 testicular cancer survivors (surveillance, 1175; chemotherapy, 897; radiotherapy, 323), median time since diagnosis 19 years, and 65,289 noncancer males were included, questionnaire response rates were 60% and 54%, respectively. There were more current smokers (prevalence ratio; 1.14, 95% confidence interval (CI): 1.03–1.26) and patients with body mass index above 25 kg/m2 (prevalence ratio; 1.10, 95% CI: 1.01–1.20) among testicular cancer survivors than in the reference population. Testicular cancer survivors reported less sedentary lifestyle (prevalence ratio; 95% CI: 0.74, 0.64–0.85) and everyday drinkers were fewer (prevalence ratio; 0.79, 95% CI: 0.68–0.92) than in the reference population. We identified smoking cessation as primary target for intervention studies in testicular cancer survivors. The effect of smoking cessation interventions as part of treatment should be investigated. Whether drug-based intervention is effective in minimising the risk of exposure to conventional risk factors for cardiovascular disease is also of interest. [ABSTRACT FROM AUTHOR]

Patients with testicular cancer (TC) are mainly young and survival rates are high. MRI has several times been proposed to replace CT in follow-up of this patient group to reduce image-related radiation exposure. However, current evidence is scarce for the use of MRI in this context. First, to retrospectively evaluate the ability of MRI of the retroperitoneum and pelvis to detect relapse in patients with TC stage I. Second, to present a relevant MRI protocol of the retroperitoneum and pelvis with diffusion weighted imaging (DWI). A retrospective analysis of written radiology reports compared to clinical data from clinical practice from 2010 to 2018. The cohort consists of 2487 MRIs of the retroperitoneum and pelvis in 759 patients with TC stage I (524 seminoma (69.0%), 235 non-seminoma (31.0%)), including 102 patients (13.4%) with confirmed relapse. Confirmed relapse was defined when treatment was initiated for metastatic TC. Ninety-five patients had a relapse in the MRI scan field during follow-up. MRI of the retroperitoneum and pelvis showed a high sensitivity of 93.8% and a high specificity of 97.4% for detecting TC relapse. The sensitivity for detecting relapse ≥10 mm in short axis lymph node diameter was 100%. The negative predictive value was 99.7%, the positive predictive value was 59.9% and the accuracy was 97.3%. MRI of the retroperitoneum and pelvis constitutes a safe alternative to CT in follow-up of patients with TC stage I with both a high sensitivity and a high specificity. We present a robust MRI protocol with DWI and estimate that MRI follow-up of TC stage I can be easily implemented in most modern radiology departments. Registration: Conducted with permission from the Danish Data Protection Agency (1-16-02-323-16) and the Danish Health Authority. [ABSTRACT FROM AUTHOR]

Introduction: To minimize the radiation exposure of mostly young testicular cancer patients, it is essential to find out whether CT could be replaced by magnetic resonance imaging (MRI) in the staging and follow-up of the patients. In this trial, we examined whether abdominal MRI is as effective as computed tomography (CT) in the detection of retroperitoneal metastases of testicular cancer. Material and methods: This prospective study included 50 patients, 46 cases of retroperitoneal metastases and 4 controls without abdominal metastases (mean age 33, 5 years, range 20–65 years). Imaging of the retroperitoneum was performed using CT and 1.5 T MRI with diffusion weighted imaging (DWI). One experienced radiologist re-analyzed all of the examinations without knowledge of clinical information. All metastatic or suspicious lymph nodes were noted and measured two-dimensionally from axial images. Nodal detection and the size of detected nodes on CT and MRI were compared. Results: There was no significant difference in the detection of retroperitoneal metastasis between CT and MRI. The sensitivity of MRI was 0.98. There was no statistically significant difference in the sizes of lymph nodes found in CT and MRI, and even very small lymph nodes could be detected in MRI as well as in CT. Conclusion: MRI with DWI is as good as CT in detection of retroperitoneal lymph node metastases regardless of lymph node size, and it can be used as part of follow-up of testicular cancer patients instead of ionizing radiation producing imaging methods. [ABSTRACT FROM AUTHOR]

Purpose: Testicular cancer survivors (TCSs) have increased risk of reduced kidney function related to treatment burden, but longitudinal studies of renal outcome in aging TCSs have been lacking. This longitudinal study describes age- and treatment-related kidney function changes in TCSs compared to a comparison group from the general population. Patients and methods: Estimated glomerular filtration rate (eGFR) was determined in blood samples from Norwegian TCSs (diagnosed 1980–1994) and surveyed median 11, 19 and 26 years since diagnosis (Survey1 [N = 1273], 2 [N = 849] and 3 [N = 670]) defining four treatment groups; Surgery only, Radiotherapy (RT) only, Cisplatin-based chemotherapy (CBCT) ≤850 mg and High CBCT/RT >850 mg cisplatin or any combination of CBCT with RT. A comparison group was constructed from similarly aged men who participated in a population-based health survey. By multiple linear regressions and generalized mixed models for repeated measurements, we studied difference in eGFR between TCSs and the comparison group for all TCSs combined and stratified by treatment modality. Results: At Survey 1, the kidney function for the youngest TCSs combined versus the comparison group was significantly reduced by mean six units (mL/min/1.73 m2) with further decline to mean 12 units at Survey 3. The kidney function was significantly reduced in all treatment groups with the largest differences emerging for TCSs from the High CBCT/RT Group, thus indicating a deteriorating impact of high cumulative doses of cisplatin. Conclusion: Collated to the comparison group, the kidney function in TCSs became increasingly impaired during nearly three post-treatment decades, related to the treatment modality. Early detection and intervention of kidney dysfunction is important to reduce the risk of TCSs' long-term morbidity and mortality related to nephrotoxicity, such as cardio-vascular diseases. [ABSTRACT FROM AUTHOR]

Background: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs. Material and methods: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment. Information about second cancers after SII was retrieved from the Norwegian Cancer Registry. Results: A larger Pt decline from SI to SII was associated with a decreased risk of a second cancer diagnosis (HR 0.78, 95% CI 0.62-0.99 per 10 ng/L/year), and worsening of paresthesias in hands (OR 1.98, 95% CI 1.09-3.59 per 10 ng/L/year) and tinnitus (OR 1.51, 95% CI 1.01-2.27 per 10 ng/L/year). Conclusion: In summary, we found a significant association between a larger Pt decline and a reduced risk of second cancers and deterioration of paresthesias in hands and tinnitus. [ABSTRACT FROM AUTHOR]

Background: Resection of residual masses after chemotherapy plays a crucial role in management of patients with germ cell tumours (GCTs). The extent of surgery is controversial and we present the experiences from Aarhus University Hospital over a 20-year period. The aim was to evaluate survival, complications, working ability and quality of life (QOL) following a limited surgical procedure performed to resect residual masses in non-seminomatous testicular cancer patients after chemotherapy. Material and methods: A consecutive patient cohort of 109 patients having surgery between 1993 and 2013 was investigated. Hospital records were reviewed and complications were graded according to the Clavien-Dindo classification. QOL data were assessed in a cross-sectional analysis using the European Organisation for Research and Treatment of Cancer (EORTC), QLQ-C30 version 3.0. Patients were matched 1:1 with controls to evaluate the influence of surgical resection on the QOL. Results: With a median follow-up of 10.3 years, 11 relapses in retroperitoneum were recorded in 10 patients (9%), and four patients (5%) died of disease progression. The majority of relapses in patients considered having no evidence of disease (NED) after primary retroperitoneal surgery occurred 10þyears after treatment and was outside the field of the elective lymph node dissection. Twentyseven (44%) grade I, 15 (24%) grade II, 7 (11%) grade IIIa and 13 (21%) grade IIIb complications were recorded. No grade IV and V complications were observed. Twenty-three patients (20%) reported loss of antegrade ejaculation. We found no significant differences between patients and controls regarding QOL. Conclusion: The survival outcome and complication rate are favourable and are comparable to studies involving full and modified template lymph node dissection. We find that limited resection constitutes an applicable and safe procedure. Limited surgical resection did not influence the patients’ long-term QOL. Longer follow-up might be considered. [ABSTRACT FROM AUTHOR]

Background: Hearing loss is a well-known long-term effect after cisplatin-based chemotherapy (CBCT) in testicular cancer survivors (TCS), but longitudinal data are sparse. We evaluate hearing loss and the impact of age in TCS treated with CBCT in this longitudinal study. Material and methods: Forty-six TCS treated with CBCT 1980-1994 with audiograms (0.25-8 kHz) prechemotherapy (PRE) and at a follow-up 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 the hearing threshold level (HTL) from PRE to SURV. Two definitions of a audiogram-defined hearing loss was applied if: (1) mean HTL for both ears exceeded 20 dB at any frequency 0.25-8 kHz (American Speech-Language-Hearing Association (ASHA) definition) and (2) average HTL for the frequencies 0.5, 1, 2 and 4 kHz exceeded 20 dB (WHO-M4 definition). Self-reported hearing impairment (SURV) was assessed by a questionnaire. Results: Age and cisplatin dose was significantly associated with a greater change in HTL for the frequencies 2-8 kHz. For the 8 kHz frequency, each 100mg increase in cumulative cisplatin dose was associated with a deterioration of 3.6 dB (95% CI 1.8-5.3, p<.001). The prevalence of hearing loss (ASHA) 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≤.049). Twenty-nine percent of cases, and 33% of controls (p≤.70) reported hearing impairment at SURV. Conclusion: Cisplatin is associated with a hearing loss particularly at higher frequencies. Age appear to be an important factor for hearing loss regardless of treatment. The ASHA definition overestimates the hearing problem. [ABSTRACT FROM AUTHOR]

Purpose:One established risk factors for testicular cancer is cryptorchidism. However, it remains unclear whether cryptorchidism is a risk factor in itself or whether the two conditions share common causes in early life (estrogen hypothesis), such as birth weight and birth order. The objective of this study is to utilize data from the Copenhagen School Health Records Register (CSHRR) to evaluate cryptorchidism, birth weight and birth order as risk factors for testicular cancer. Methods:The study population consisted of 408 cases of testicular cancer identified by a government issued identification number linkage of the entire CSHRR with the Danish Cancer Registry and a random subsample of 4819 males from the CSHRR. The study design was case-cohort and the period of follow-up between 2 April 1968 and 31 December 2003. Results:Cryptorchidism was significantly associated with testicular cancer in crude analyses [hazard ratio (HR) = 3.60, 95% CI 2.79–4.65]. Birth weight was inversely associated with testicular cancer and no clear association with birth order was observed. The positive association between cryptorchidism and testicular cancer was only slightly attenuated controlling for birth weight and birth order and stratified on birth cohort (HR = 3.46, 95% CI 2.67–4.48). Conclusion:This study confirmed the robustness of the association between cryptorchidism and testicular cancer even after adjustment for birth weight and birth order. Furthermore, the study showed an inverse association between birth weight and testicular cancer. [ABSTRACT FROM PUBLISHER]

The article evaluate the prevalence of thyroid hypofunction among a cohort of Norwegian testicular cancer survivors take advantage of results in a normative Norwegian population as well as linkage to the Norwegian Prescription Database. Topics include testicular cancer diagnosis, the prevalence of thyroid hypofunction was in the testicular cancer survivors; and overall risk of thyroid hypofunction related to the type of cytotoxic testicular cancer treatment with cisplatin-based chemotherapy.

Background.Whole body (WB) magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) has become increasingly utilized in cancer imaging, yet the clinical utility of these techniques in follow-up of testicular cancer patients has not been evaluated. The purpose of this study was to evaluate the feasibility of WB MRI with continuous table movement (CTM) technique, including multistep DWI in follow-up of patients with testicular cancer. Patients and methods.WB MRI including DWI was performed in follow-up of 71 consecutive patients (median age, 37 years; range 19–84) with histologically confirmed testicular cancer. WB MRI protocol included axial T1-Dixon and T2-BLADE sequences using CTM technique. Furthermore, multi-step DWI was performed using b-value 50 and 1000 s/mm2. One criterion for feasibility was patient tolerance and satisfactory image quality. Another criterion was the accuracy in detection of any pathological mass, compared to standard of reference. Signal intensity in DWI was used for evaluation of residual mass activity. Clinical, laboratory and imaging follow-up were applied as standard of reference for the evaluation of WB MRI. Results. WB MRI was tolerated in nearly all patients (69/71 patients, 97%) and the image quality was satisfactory. Metal artifacts deteriorated the image quality in six patients, but it did not influence the overall results. No case of clinical relapse was observed during the follow-up time. There was a good agreement between conventional WB MRI and standard of reference in all patients. Three patients showed residual masses and DWI signal was not restricted in these patients. Furthermore, DWI showed abnormally high signal intensity in a normal-sized retroperitoneal lymph node indicating metastasis. The subsequent18F-FDG PET/CT could verify the finding. Conclusion.WB MRI with CTM technique including multi-step DWI is feasible in follow-up of patients with testicular cancer. DWI may contribute to important added-value data to conventional MRI sequences regarding the activity of residual masses. [ABSTRACT FROM PUBLISHER]

Purpose.To investigate if testicular cancer survivors (TCSs) have a higher incidence of work loss compared with the population, accounting for stage, treatment and relapse. Material and methods.A cohort of 2146 Swedish TCSs diagnosed 1995–2007 (seminoma n = 926, non-seminoma n = 1220) was identified in the SWENOTECA (Swedish-Norwegian Testicular Cancer Group) register, and matched 1:4 to population comparators. Prospectively recorded work loss data (both before and after diagnosis) were obtained from national registers through September 2013. Adjusted relative risks (RR) and 95% confidence intervals (CI) of sick leave and/or disability pension were calculated annually and overall with Poisson- and Cox regression, censoring at relapse. The mean number of annual work days lost was also estimated. Results.TCSs were at a modestly increased annual risk of work loss up to the third year of follow-up (RR3rd year1.25, 95% CI 1.08, 1.43), attributed to a more pronounced risk among extensively treated patients (4 chemotherapy courses: RR3rd year1.60, 95% CI 1.19, 2.15; > 4 courses: RR3rd year3.70, 95% CI 2.25, 6.11). Patients on surveillance or limited treatment (radiotherapy, 1–3 chemotherapy courses) did not have an increased risk of work loss beyond the first year. TCSs receiving > 4 chemotherapy courses had higher mean number of annual days of work loss up to the 10th year post-diagnosis, and a five-fold risk of disability pension (RR 5.16, 95% CI 2.00, 10.3). Conclusion.Extensively treated TCSs, but not those on surveillance or limited treatment, are at increased risk of work loss long-term, not explained by relapse. These patients may benefit from early rehabilitation initiatives. [ABSTRACT FROM PUBLISHER]

Background. Treatment of testicular germ cell cancer constitutes a major success story in modern oncology. Today, the vast majority of patients are cured by a therapeutic strategy using one or more highly effective components including surgery (orchiectomy), radiotherapy and/or chemotherapy. However, the excellent cancer-specific survival comes at considerable costs, as individuals with a history of germ cell cancer experience serious long-term complications, including markedly increased risk of cardiovascular morbidities and premature cardiovascular death. The factors responsible, as well as their mode of action, are not fully understood and there is a lack of knowledge concerning optimal evidence-based long-term follow-up strategies. Results. Here, we present the growing body of evidence suggesting that germ cell cancer patients as a consequence of the different treatment components, are subjected to toxicities, which individually, and synergistically, can cause physiological impairments leading to sub-clinical or clinical cardiovascular disorders (i.e. the 'multiple-hit hypothesis'). Furthermore, we discuss the efficacy and utility of structured exercise training to ameliorate treatment-induced cardiovascular dysfunction to prevent premature onset of clinical cardiovascular disease in germ cell cancer survivors, with a view towards highlighting future directions of exercise-based survivorship research in the germ cell cancer setting. Conclusion. As exercise training may have the potential to ameliorate and/or reverse long-term cardiovascular disease sequelae in germ cell cancer survivors, a strong rationale exists for the promotion of exercise oncology research in this setting, in order to provide exercise recommendations for optimal germ cell cancer survivorship. [ABSTRACT FROM AUTHOR]

Background. A contralateral tumor occurs in 3.5-5% of men diagnosed with testicular germ cell cancer (TGCC). Biopsy of the contralateral testis may detect intratubular germ cell neoplasia ITGCNU, a precursor of TGCC. Biopsy of the contralateral testis to detect ITGCNU is controversial. If adjuvant chemotherapy (ACT) protects against bilateral cancer is debated. Material and methods. A total of 1003 patients with clinical stage I (CS I) non-seminomatous testicular germ cell cancer (NSGCT) were included in two prospective, population-based protocols. Fifteen patients were excluded. Treatment was either adjuvant chemotherapy (n = 494), or surveillance (n = 494). Contralateral testicular biopsy was recommended for all patients, but was performed only in 282 patients. In case of ITGCNU radiotherapy (RT) to 16 Gy was recommended. Results. During a follow-up of 8.3 years, 31 (3.6%) patients developed contralateral TGCC. ITGCNU was detected in 3.2% (9/282) of biopsied patients. The incidence of bilateral TGCC was similar following ACT, 2.5% (11/494), and surveillance, 3.4% (13/494), p = 0.41. Young age was a risk factor for metachronous TGCC (HR 0.93; 95% CI 0.88-0.99, p = 0.02). In total 2.2% (6/273) of patients without ITGCNU in the biopsy developed contralateral TGCC. One irradiated patient developed contralateral cancer, and one developed contralateral tumor before RT was given. Conclusion. ACT did not reduce the incidence of contralateral TGCC. Young patients had the highest risk of developing contralateral TGCC. The proportion of false negatives biopsies was higher than reported in earlier trials, but this may in part be related to patient selection, single biopsies and lack of mandatory immunohistochemistry. [ABSTRACT FROM AUTHOR]

The author reflects on the developments in testicular cancer management and treatment as of June 2021. Other topics include the introduction of cisplatin-based chemotherapy, the updated prognostic factors for disseminated germ cell cancer (GCC), and the collaboration among surgical and medical oncology societies in the advancements of testicular cancer management.

Background. Following restoration of political independence in 1990, Lithuania underwent rapid societal and economic changes. We aimed to assess trends in cancer survival in the first two decades following these changes. Material and methods. We used population-based data from the Lithuanian Cancer Registry and period analysis techniques to examine trends in one-, 2-5- and five-year relative survival between 1995-1999 and 2005-2009 for 24 common cancers in Lithuania. Results. Between 1995-1999 and 2005-2009, five-year relative survival increased significantly for 20 of 24 cancers, and for 10 cancers the increase exceeded 10% units. Five-year relative survival estimates reached 46%, 69% and 91% for colorectal, breast and prostate cancer in 2005-2009, respectively, while patients with testicular cancer, Hodgkin's or non-Hodgkin's lymphoma had a five-year relative survival of 77%, 75% and 50%, respectively. Conclusion. We found a rapid increase in survival for most forms of common cancers in Lithuania between 1995 and 2009. Nevertheless, several cancers with effective therapies exhibit considerable gaps compared with Northern and Western European countries. Despite ongoing rises in survival, mortality declines are not yet manifesting for important common cancers such as breast and colorectal cancer. Rapid incidence rises suggest that increases in survival for prostate and thyroid cancers are massively influenced by early detection-related effects. Improving the availability of effective therapies, and carefully planned early detection programs may help to increase cancer survival in Lithuania in the future. [ABSTRACT FROM AUTHOR]

Background. Testicular cancer survivors treated with chemotherapy are at increased risk for metabolic syndrome (MetS) and cardiovascular disease (CVD). We explored acute effects of chemotherapy by assessing metabolic factors, abdominal fat volume, hepatic triglyceride content (HTC) and aortic wall stiffness. Material and methods. We studied 19 testicular cancer patients (age 20-54 years) before, at three and nine months after the start of chemotherapy. Blood serum was analyzed for lipids, glucose and insulin. Abdominal visceral and subcutaneous fat volume and aortic pulse wave velocity were assessed by magnetic resonance imaging (MRI) techniques; HTC was measured by proton MR spectroscopy. Results. Three months after start of chemotherapy visceral abdominal fat volume had significantly increased from 202 ± 141 to 237 ± 153 ml (p = 0.009) whereas body mass index and subcutaneous fat volume significantly increased nine months after treatment from 24.4 ± 4.0 to 26.4 ± 4.1 kg/m2 (p = 0.01) and from 556 ± 394 to 668 ± 460 ml (p = 0.002) respectively. Serum total cholesterol, low-density lipoprotein cholesterol and insulin also significantly increased three months after start of treatment from 4.88 ± 1.1 to 5.61 ± 1.50 mmol/l (p = 0.002), 3.31 ± 1.16 to 3.73 ± 1.41 mmol/l (p = 0.02) and 5.7 ± 4.4 to 9.6 ± 6.3 mU/ml (p = 0.03), respectively. Nine months after start of chemotherapy serum lipid and insulin concentrations had returned to baseline. HTC increased in seven of the 19 patients (36.8%) during follow-up. Aortic pulse wave velocity remained unchanged at the three time points measured. Conclusion. Cisplatin-based chemotherapy was associated with acute insulin resistance, dyslipidemia and an immediate increase in abdominal visceral adipose tissue and abdominal subcutaneous adipose tissue in testicular cancer patients. A large prospective cohort study with long follow-up is warranted to characterize the time course and relationship between acutely induced obesity and hypercholesterolemia and the development of metabolic syndrome and CVD years later in individual testicular cancer survivors. [ABSTRACT FROM AUTHOR]

Background. Worldwide marked changes have been observed in the incidence and survival of testicular cancer (TC) during the last decades. We conducted a study on trends in TC incidence, treatment, survival, and mortality in the Netherlands during the period 1970-2009 with specific focus on trends according to age, histology and stage of disease. Methods. Data from the Eindhoven cancer registry, the Netherlands cancer registry and Statistics Netherlands was used. Age-standardized incidence and mortality rates and five-year relative survival were calculated. Treatment was categorized into five major groups. Results. TC incidence showed a substantial annual increase of 3.9% in the period 1989-2009. The incidence increased for all stages of both seminoma and non-seminoma TC. Stage distribution for the non-seminoma patients shifted towards more localized disease. Most patients received primary treatment according to the guidelines. Five-year relative survival improved (non-significantly) for most groups of stage and histology. TC mortality dropped sharply in the 1970s and 1980s and remained relatively stable thereafter. Conclusion. This study shows that incidence of TC has increased sharply in the Netherlands. Relative survival is high and improved in most disease stages. There is a growing demand for medical care of newly diagnosed TC patients and for the rapidly increasing number of prevalent TC patients. [ABSTRACT FROM AUTHOR]

The article presents commentary on Thyroid hypofunction in aging testicular cancer survivors. Topics include findings are not against a hypothesis of in utero endocrine disrupting exposure as an etiology for testicular dysgenesis and thyroid dysfunction; and followed-up proposal of additional analyses of the hypothyroidism in 148 Testicular Cancer Survivors (TCSs) after surgery.

Background. Studies suggest an increased risk for compromised cognitive function among cancer survivors. It is unclear to what extent chemotherapy is the cause and how the dysfunction, when present, affects everyday life. The objective was to study self-reported behaviours that may depend on cognitive function, among testicular-cancer survivors who received various cycles of cisplatin-based chemotherapy by comparing them with those who did not. Material and methods. We identified 1173 eligible men diagnosed with non-seminomatous testicular cancer treated according to the national cancer-care programs SWENOTECA I-IV between 1981 and 2004. During an 18-month qualitative phase we constructed a study-specific questionnaire including questions about specific activities and behaviour in everyday life. Results. We obtained information from 960 of 1173 (82%) testicular-cancer survivors diagnosed on average 11 years previously. The prevalence of 'saying similar but incorrect words' at least once a week was 5% among those having received no chemotherapy versus 16% among those having received five or more cycles, giving a prevalence ratio ('relative risk', RR) of 3.3 with a 95% confidence interval of 1.5 to 7.1. The corresponding figure for 'saying words in the wrong order' was 3.1 (1.7-5.8), for 'difficulties understanding what other people mean' 3.1 (1.3-7.7), for 'saying words other than planned' 2.2 (1.1-4.5) and for 'difficulties completing sentences' 2.0 (1.0-3.6). The relative risks for those with a low level of education ranged between 4.9 (1.6-14.9) and 15.3 (1.9-120.5). Conclusion. Testicular-cancer survivors in Sweden who have received five or more cycles of cisplatin-based chemotherapy experience an increased incidence of long-term compromised language; the effect is primarily seen among men with a low level of education. [ABSTRACT FROM AUTHOR]

Background. The SWENOTECA IV protocol from 1995 is a prospective population-based study in metastatic non-seminomatous germ cell testicular cancer (NSGCT), designed for early identification of patients with poor response to standard cisplatin-based chemotherapy. A slow tumor marker decline (HCG T½ > 3 days, AFP T½ > 7 days) after BEP or BEP plus ifosfamide was regarded as poor response. The aim of this study was to present survival and toxicity data for patients treated with high-dose chemotherapy (HDCT) within the SWENOTECA IV cancer care program. Material and methods. In total 882 adult men diagnosed with metastatic NSGCT between July 1995 and June 2007 in Sweden and Norway (except one center) were included in SWENOTECA IV and treated accordingly. Among these, 55 men (6.2%) were treated with HDCT according to three different indications in the protocol: A) poor response to standard-dose intensified chemotherapy (BEP plus ifosfamide); B) vital cancer at surgery after intensified chemotherapy; and C) selected relapses after previous chemotherapy. In situation A and C two HDCT cycles and in situation B one HDCT cycle was recommended. Situation A was the reason for HDCT in 36 patients, B in seven and C in 12 patients. The first HDCT cycle consisted of carboplatin 28 × (GFR ++ 25) mg, cyclofosfamide 6000 mg/m2 and etoposide 1750 mg/m2, administered over four days. In cycle two, etoposide was replaced by tiotepa 480 mg/m2. Results. After a median follow-up of 7.5 years, overall survival was 72%, 100% and 58%, while failure-free survival was 64%, 71% and 42% in situation A, B and C, respectively. Three patients (5.5%) died during HDCT (renal failure or intracerebral hemorrhage). Nephrotoxicity was the most common non-hematological grade 4 toxicity (n == 5, 9%). Conclusion. The population-based SWENOTECA strategy, selecting patients who do not respond adequately to primary standard-dose chemotherapy for immediate treatment intensification with HDCT, is feasible and might be advantageous. [ABSTRACT FROM AUTHOR]

The authors reflect on testicular cancer and on testicular germ cell tumors. They suggest that a large geographical variation in the incidence of testicular germ cell cancers has puzzled researchers who are interested in testicular cancer epidemiology. They argue that in 2012 there are still many questions which need to be answered regarding testicular cancer and its treatment and that medical professionals should be encouraged by progress which has been made in the area since 1982.

Background. The etiology of testicular germ cell cancer (TGCC) is still poorly understood, but biological and epidemiological evidence suggest that TGCC originates early in life. The aim of the present study was to analyze heterogeneity in TGCC risk within Norway, comparing county of birth to county of diagnosis, in order to assess the relative contribution of risk factors acting early and later in life. A further aim was to present the Norwegian TGCC incidence rates (1958-2007). Material and methods. All TGCC cases (n == 7130) reported to the Cancer Registry of Norway, 1958-2007, were analyzed by county of diagnosis in 10-year intervals. The relative risk of TGCC based on county of birth, was estimated by Poisson regression analysis of all new TGCC cases (n == 1943), based on the mother's county of residence at the time of the son's birth, 1967-2007, obtained by linkage between the Cancer Registry and the Medical Birth Registry of Norway. Results. Between the first (1958-67) and last (1998-2007) 10-year period, the average incidence rate more than tripled from 3.3 to 10.5 per 100 000 person-years (world adjusted), respectively. The average incidence rate during 1968-2007 was highest in the county of Rogaland (8.6) and lowest in Hedmark (5.3), the ratio between them being 1.6. The relative risk of TGCC based on county of birth (1967-2007) varied between 1.43 (Møre og Romsdal) and 0.95 (Buskerud), giving a ratio of 1.5. Conclusions. The ratio between the relative risk in the highest and lowest county was basically similar when comparing counties of birth with counties of diagnosis. Thus, our data do not shed light on the relative contribution of risk factors acting early versus later in life. The incidence rate of TGCC in Norway is among the highest in the world, and the increase in incidence rate does not seem to level off. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented which is concerned with testicular cancer and the tuberous sclerosis complex.

Background. International comparisons have pointed to very low survival of patients diagnosed with testicular cancer (TC) in Estonia. Methods. Using population based data from the Estonian Cancer Registry and period analysis, we examined trends in TC survival between 1985 and 2004. Additional results from a review of clinical records to ascertain patterns of disease management (1990-2003) were used to explain the changes and identify the areas for potential improvement. Results. Age-adjusted 5-year period relative survival increased from 47.9% in 1985-1989 to 74.5% in 2000-2004 (p for trend <0.01). A marked improvement was seen for the patients younger than 30, with the 5-year survival reaching 93.3%, while the improvement remained modest among patients aged 30 and above. Although substantial advances occurred in staging and treatment techniques since 1990, deficiencies remained evident in disease management, including not referring patients to an oncologist after their orchiectomy and less careful diagnostic workup for patients above 30 years of age. Low use of radiotherapy suggests poor access to contemporary equipment. Delays in seeking medical consultation, but also in starting adjuvant therapy, could have contributed to poorer outcomes. Conclusions. Survival in TC increased markedly in Estonia by the 21st century, but is still notably lower than in the more developed countries. Multidisciplinary efforts may help to achieve further improvement. The provision of TC care should be coordinated by specialised cancer centres. [ABSTRACT FROM AUTHOR]

The clinical significance of serum neuron-specific enolase (NSE) was evaluated at diagnosis (before orchiectomy) in 132 patients, and in the follow-up of 236 men with germ cell tumours of the testis. The purpose of the study was to determine whether serum NSE was a more clinically useful tumour marker than the existing tumour markers β-hCG, AFP and LDH. The mean observation time was 4.3 years. At orchiectomy, serum NSE levels were raised in 38 (29%) of all the patients, and in 8/53 (15%) of the patients with clinical stage 1 seminoma. NSE had the same sensitivity as β-hCG in seminoma. There were very few false-positive values for the classic markers β-hCG and AFP, but 117 out of 219 patients (53.5%) did experience false-positive serum NSE levels at least once during follow-up. The false-positive values were wide ranging [13-70 μg/L]. None of the four evaluable patients with seminoma who experienced relapse had increased levels of serum NSE at relapse. Two out of 14 non-seminoma patients who experienced relapse had elevated serum NSE levels at the time of relapse, but increased NSE was not the first sign of relapse in any of them. It is concluded that serum NSE is of no clinical value in monitoring patients with testicular cancer. [ABSTRACT FROM AUTHOR]

Decrease in serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels is considered as a response during chemotherapy of non-seminomatous germ cell testicular tumors, but data on the prognostic significance of marker half-life remains inconclusive. Serum marker half-life was evaluated in 34 patients with elevated markers, receiving chemotherapy (CT). Marker half-life was calculated from the natural logarithm of the sequential AFP or HCG concentrations. The correlation between event-free (EFS) and overall survival (OS) with unfavorable half-lives of AFP and HCG was evaluated. Median actual half-life (AHL) AFP was 3.9 days (range, 1.4-21.5) and median AHL HCG was 4.4 days (range, 1.4-21.0); 82% of the patients had a satisfactory initial decline in AFP, and 71% had a satisfactory initial decline in HCG. There was a significant difference in EFS and OS between the two groups of patients with an AFP half-life <7 days and >7 days. HCG half-life did not adversely affect EFS and OS. The correlation of better EFS and OS with appropriate AFP marker half-life during chemotherapy could provide a dynamic method, which could complement the standard baseline prognostic factors, for the prediction of prognosis. [ABSTRACT FROM AUTHOR]

Testicular primary non-Hodgkin's lymphoma (NHL) is said to account for about 5% of all testicular tumors and about 2% of extranodular lymphoma. From a clinical standpoint, we reviewed testicular NHL of stage IE treated at our department over the past 18 years. Among the 865 cases of NHL, 19 (2.2%) were primary testicular NHL, stage IE. The 19 patients had a median age of 62 years (range 48-77 years), all had diffuse B-cell lymphoma. Of the 19 patients, 8 were treated with radiotherapy after high inguinal orchiectomy (Group I), 4 received both postoperative radiotherapy and chemotherapy (Group II), and 7 received additional prophylactic intrathecal chemotherapy (Group III). The 5-year survival rates for Groups I, II and III were 37.5%, 50%, and 100%, respectively. None of the patients receiving prophylactic intrathecal chemotherapy had relapse in the central nervous system and all of them are alive and disease-free. Primary testicular NHL is relatively common among elderly persons, and many patients die as a result of central nervous system recurrence. These results suggest that preventive measures for central nervous system recurrence such as intrathecal injection of anticancer agents should be taken into consideration as early as at the induction of remission. [ABSTRACT FROM AUTHOR]

The article looks at patterns of testicular cancer mortality in Europe, noting that disparities between outcomes in Eastern and Western Europe persist despite the success of cisplatin treatments. The estimated annual percent change (EAPC) of age-standardised testicular cancer mortality rates over thirty years was calculated for 21 European countries, including the highest rates for Bulgaria and the Republic of Moldova and the lowest in Luxembourg and Iceland.

The article presents a case study of a 19 year old patient who was admitted to a hospital after having suffered a convulsive fit. A discussion of diagnostic testing which was conducted on the patient, and which resulted in him receiving a diagnosis of multifocal intracranial germinoma with raised tumour markers in serum but not in CSF and with carcinoma in situ of the testis, is presented.

A letter to the editor is presented which is concerned with a case of sarcoidosis in a patient with testicular cancer post stem cell transplant.