There have been significant advances in the treatment of testicular cancer in recent decades, such that >97% of individuals can expect a cure [1-3]. While being cancer free, survivors may experience physical, psychological, and social consequences that persist long after their diagnosis and treatment, including cardiovascular morbidity, hypogonadism, second malignancy, and residual chemotherapy toxicities [4-9]. Psychological distress is common immediately following diagnosis [10-13], with a large retrospective study of survivors of testicular cancer suggesting that distress was most significant at this time compared with other periods of their cancer journey [13]. Distress is multifactorial; however, it frequently stems from a perceived lack of information regarding treatment and prognosis [14] and is influenced by risk factors including education level, chronic illness, absence of paid employment, relationship status, and treatment-related factors, such as concomitant use of chemotherapy [6,9,15-18]. Importantly, some individuals may experience persistent symptoms leading to chronic anxiety and depression [19], such that the prevalence and severity of anxiety reported in long-term survivors of testicular cancer is higher than in the general population, with up to 21% of survivors reporting persistent symptoms [9].

Existing support for distress focuses on these long-term survivors, leaving individuals shortly after their diagnosis without adequate resources to support their distress, if required [13,20]. Multiple studies have demonstrated that psychosocial interventions or support help reduce anxiety and depression in people with cancer generally [21-23], and in long-term survivors of testicular cancer [24,25]. However, intervention uptake is variable, particularly in males and young adults [26-29], which may stem from differences in coping strategies and help-seeking behavior and the influence of social gender norms. In addition, there is a lack of age-appropriate and sex-sensitized support for younger people diagnosed with testicular cancer [30,31], further widening this gap and accentuating the need for support to help manage distress proactively and promote long-term psychological health. With this in mind, a pilot study of a web-based psychological intervention in long-term survivors of testicular cancer demonstrated promising acceptability; however, feasibility was limited by poor engagement with the intervention, as evidenced by low module completion rates over time [25]. Where survivors of testicular cancer frequently survive for many decades following curative treatment [32], it is integral to develop novel strategies to adequately address distress at the outset in those who need assistance.

Nuts & Bolts is a web-based intervention funded and operated by the Movember Foundation that could help address this unmet need in patients with recently diagnosed testicular cancer [33]. The intervention comprised the following three domains:

The website requires individuals to self-navigate through the 3 domains according to their specific needs. It was not readily available to the public at the time this study was recruiting; however, the website has since been made available following an official launch.

We undertook a prospective, multicenter, randomized controlled trial to evaluate the acceptability, feasibility, and impact of Nuts & Bolts on distress levels in the weeks following diagnosis of testicular cancer; however, because of poor accrual and anticipated impacts of the COVID-19 pandemic on research personnel, the trial closed early. We then evaluated the prevalence of distress, anxiety, and depression following a recent diagnosis of testicular cancer, changes in symptoms across a period of observation, and an exploration of the lived experience of individuals with newly diagnosed testicular cancer through thematic analysis of semistructured interviews.

This study was designed as a mixed methods, convergent parallel, randomized controlled trial. Eligible participants were aged >18 years, had histologically confirmed testicular cancer within 4 weeks of study consent, were proficient in English and had access to the internet.

Eligible participants were assigned (1:1) to either early intervention with access to Nuts & Bolts at the time of study consent or delayed intervention, in which access was provided 1 week later. Once access was provided, participants were expected to self-navigate the website according to their specific needs.

Quantitative data were collected using the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) score (0-10) and problem list [34], as well as the Hospital Anxiety and Depression Scale–Anxiety (HADS-A) score (0-21), Hospital Anxiety and Depression Scale-Depression (HADS-D) score (0-21), and Hospital Anxiety and Depression Scale-Total score (0-42) [35]. Participants completed assessments on a web-based portal at study consent and after 1, 2, 4, and 5 weeks, which varied by the assigned study group (Figure 1).

The primary end point was the change in DT score between study consent and day 8 in the early intervention group, compared with the control, delayed intervention group. Key secondary end points included changes in DT, HADS-A, and HADS-D scores between study consent and day 8 and introduction to Nuts & Bolts and 4 weeks later. Owing to poor accrual, a descriptive analysis of the results obtained from all enrolled participants, regardless of group assignment, was performed. In addition, the acceptability and usability of Nuts & Bolts were evaluated using a supplemental questionnaire delivered after the period of observation.

Qualitative data were collected after completion of the quantitative assessments. Participants were invited to undertake optional, ethically approved semistructured interviews, which were thematically analyzed [36] to explore the lived experiences of individuals following the diagnosis of testicular cancer. Consenting participants were invited to be interviewed using convenience sampling until data saturation was reached. Interviews were undertaken (interviewer was female, registered nurse and research coordinator; see the Acknowledgments section) in accordance with the consolidated criteria for reporting qualitative research recommendations [37]. Telephone interviews lasting 20 to 30 minutes were audio recorded. The interviewer had previous contact with all participants in her role as a research coordinator before the interview; no relevant biases were reported.

We estimated that a sample of 86 participants, allowing for a 20% loss to follow-up, would provide ≥80% power to detect a mean difference of 1.8 between early and delayed intervention groups when a change in DT scores from baseline to day 8 were assessed using analysis of covariance where study arm and baseline DT score treated as covariates. In addition, linear regression was performed to explore the impact of the study arm and baseline DT score on the reduction in DT. Other quantitative data were analyzed using simple descriptive statistics. Odds ratios (ORs) were used to explore associations among categorical data, and the log method was used to calculate 95% CIs. For comparisons of mean scores between time points and subgroups, paired or independent 2-tailed t tests were used and are further outlined in the Results section. Statistical significance was defined as a 2-tailed P value of ≤.05. All statistical analyses were performed using Stata (version 14.2; IBM Corp) and Microsoft Excel for Mac (version 16.5).

Qualitative semistructured interview data were thematically analyzed, systematically identifying, organizing, and providing insight into patterns of meaning (themes) across the data set [36]. Interview transcripts were independently coded using NVivo (version 10; QSR International) by a member of the research team naïve to intervention allocation. A subset of the interviews (n=3) was coded by a second researcher to ensure concordance, and differences in coding were resolved through discussion. The themes were derived from the data. A constant comparative method involving moving back and forth between the interview transcripts, coded data extracts, and themes generated was used to ensure that the thematic hierarchy accurately reflected the interview data. Subthemes and themes were finalized in discussions with a second researcher to reduce the risk of individual biases affecting the results. The participants did not provide feedback on the findings.

Study data were collected and managed using REDCap (Research Electronic Data Capture; Vanderbilt University) [38,39], electronic data capture tools hosted by the Clinical Translation Centre, Walter and Eliza Hall Institute of Medical Research.

This study was approved by the Melbourne Health Human Research Ethics Committee (MH-2018-157301). Local ethical and governance approval was obtained from all participating sites. All participants provided written informed consent based on the Declaration of Helsinki principles [40] and were not financially compensated for their involvement in the study. All data collected during the study were deidentified; participants were provided with a unique identification code at the time of registration.

Between April 2019 and April 2020, of the 56 invited participants, 39 (70%) participants from 4 sites consented to the trial and were randomly assigned to early intervention (20/39, 51%) or delayed intervention (19/39, 49%; Figure 2). The accrual was closed early because of the anticipated impact of the COVID-19 pandemic on research personnel and hospital resources at coordinating and recruiting centers. Overall, 119 study questionnaires were completed during the observation period, and 95% (37/39) of the participants completed all study assessments. The median participant age was 32 (range 24-55) years, and the median time from orchidectomy was 14.8 (range 3-62) days at study consent (Table 1). In all, 5% (2/39) of the participants were enrolled >4 weeks after the diagnosis of testicular cancer (enrollment violation).

Distress identification is vital when caring for patients diagnosed with cancer [19]. Our study of individuals with recently diagnosed testicular cancer found that more than half of the participants reported moderate distress at the time of study enrollment, with the highest distress observed in participants within 14 days of orchidectomy, as in previous research [10-13]. Reassuringly, distress levels decreased over time, with a significant change in mean DT scores seen throughout the course of observation and as time increased from diagnosis, with only 13% (5/38) of the participants reporting moderate distress after 1 week of observation (approximately 3 weeks after orchidectomy). Notably, depressive symptoms were less common than anxiety in our cohort, which mirrors existing research [6,41].

Although the primary outcome of this study was not met and earlier introduction to Nuts & Bolts did not lead to a significant reduction in distress on day 8, thematic analysis of semistructured interviews occurring after completion of quantitative assessments emphasized a high level of perceived utility for Nuts & Bolts. Multiple participants indicated a strong preference for access to Nuts & Bolts at the time of diagnosis, when their distress was highest, while acknowledging its usefulness during and after treatment. Importantly, the introduction of Nuts & Bolts did not negatively affect distress, and thematic analysis and poststudy evaluations strongly endorse its ongoing role in supporting individuals following the diagnosis of testicular cancer. Partnerships between researchers and nongovernment and industry organizations are key to the sustained dissemination of web-based interventions in cancer care [42]. As this study was completed, Movember has formally launched and promoted the availability of Nuts & Bolts.

Making Nuts & Bolts available to individuals earlier in the process of diagnosing and treating testicular cancer may increase its clinical utility. The perceived “late” introduction to Nuts & Bolts may have lessened its clinical utility. A preference for earlier intervention, that is, before orchidectomy, was highlighted by participants in semistructured interviews and may be appropriate to help ameliorate the significant distress and whirlwind of diagnosis they experience in some individuals where a testicular cancer diagnosis is strongly suspected based on preoperative information. Other studies evaluating psychological interventions for the management of distress in patients with cancer, have similarly highlighted that earlier interventions lead to reduced stress, improved quality of life, and superior clinical outcomes [18]. With conflicting reports regarding the prevalence of long-term distress in survivors of testicular cancer [9,10,43], early intervention is important for those who wish to receive it. In addition, as a clinical trial requiring consent, the study may have introduced a potential selection bias for “active copers” rather than individuals with passive coping strategies [6], which may be reflected in the 70% (39/56) response rate for study involvement. These individuals are likely to seek additional information following their diagnosis as opposed to individuals with passive coping strategies. Sociodemographic information of nonconsenting individuals was not collected.

The potential sources of distress elicited from participants were wide ranging, with domains of emotional problems, such as nervousness, worry, fear and sadness and physical problems, such as pain, fatigue and “feeling swollen” dominating the NCCN problem list tool at study entry. Notably, these stressors reduced over time, with a comparatively small number of participants reporting these problems after 4 weeks of observation. This may relate to the resolution of postoperative symptoms, particularly pain and “feeling swollen,” and adjustment to the new diagnosis over time. In addition, thematic analysis revealed important concerns regarding communicating with family and friends, fear of cancer recurrence or spread, potential toxicity from chemotherapy, and risks posed by the COVID-19 pandemic while undergoing treatment. Although only raised by a small number of participants in the semistructured interviews in our study, previous research has identified significant concerns about fertility and sexual health following a cancer diagnosis [44-47], which is relevant to survivors of testicular cancer. Regardless, Nuts & Bolts was able to address multiple sources of distress for some participants by providing accurate information about their diagnosis, treatment options, and prognosis, while others relied on their health care team, alternate resources, and family or friends to fill these gaps.

Overall, Nuts & Bolts was considered relevant, user-friendly, and acceptable by most participants. These findings are consistent with previous studies, which reported high levels of patient satisfaction with web-based and mobile-based psychosocial interventions [48-55], particularly those encouraging patient empowerment [56], such as Nuts & Bolts. This is significant for survivors of testicular cancer, given the barriers to engagement that this unique cohort faces over and above other populations with cancer [26-31]. As almost all individuals recruited in our study reported ethnicity, individuals from culturally and linguistically diverse backgrounds may require alternate support geared toward their needs in the future.

Our study had several strengths, including its prospective design with limited missing data and the inclusion of a mixed methods analysis derived from questionnaires and thematic analysis of semistructured interviews highlighting key issues for survivors after diagnosis. Unfortunately, owing to poor accrual and anticipated impacts of the COVID-19 pandemic on hospital resources and recruiting and coordinating centers, the study was closed early, and consequently, the primary end point was underpowered, and we were unable to draw firm conclusions about the differential impact of Nuts & Bolts on distress after 1 week. The instruments that have been validated in multiple clinical settings may also have been too crude to adequately evaluate changes over a short period, which may have also limited the interpretation [57].

In addition, our primary end point may have been inadvertently hampered by the study design. When designing the study, we felt that withholding access to a potentially valuable clinical resource from patients in the delayed group for more than 1 week was unethical. Although the baseline characteristics were balanced across both groups, our results showed that distress was highest in participants who were enrolled within 14 days of orchidectomy, and the baseline level of distress was the only covariate associated with a significant decline in DT score after 1 week of observation. Therefore, a 1-week delay in the introduction of Nuts & Bolts from the time of study consent was unlikely to have a significant impact on distress. Instead, prospectively enrolling participants before orchidectomy to ensure that questionnaires were completed at uniform periods postoperatively may have overcome this; however, this approach risked missing potential participants owing to the rapidity of diagnostic workup and delays in referral for the trial. Despite this limitation, the thematic analysis of semistructured interviews and observation over time of individuals’ distress following a recent testicular diagnosis adds valuable data to the literature and remains a significant strength.

High levels of distress are observed following a diagnosis of testicular cancer; however, this decreases over time. Nuts & Bolts is an acceptable and feasible tool to help address distress in individuals recently diagnosed with testicular cancer, empowering them to seek information relating to their diagnosis and potentially improve preparedness for treatment using a model appropriate for its target population. The optimal timing of introduction remains unclear; however, early access to appropriate support appears to be key to maximizing benefit and ameliorating the whirlwind associated with diagnosis and treatment. On the basis of these outcomes, the intervention was rolled out in a broader community of individuals diagnosed with testicular cancer.