Quality of life, voiding and sexual function of penile cancer patients: DaPeCa‐10—a cross‐sectional questionnaire survey

Abstract Objectives To assess prevalence of voiding and sexual symptoms and quality of life in penile cancer patients. Methods From 1 January 2013 to 31 December 2015, we approached three separate groups of Danish penile cancer patients and asked them to complete a face‐validated questionnaire at diagnosis (Group 1), after 1 year (Group 2) and after 2 years (Group 3). We analysed symptom prevalence and bother and quality of life items and explored differences between groups. Results In total, we analysed 157 questionnaires. The response rates at diagnosis, after 1 year and after 2 years were 29%, 46% and 30%. The pad use (p = 0.001) and occurrence of nocturia twice a night or more (p = 0.006) was significantly decreasing 2 years after treatment. There was an increasing trend in sexual thoughts and importance of sexuality from 1 to 2 years after treatment, but the proportion of patients reporting a frequency of orgasm at more than once in the past 6 months was significantly decreasing after treatment (p = 0.03). Likewise, the trend for erectile dysfunction worsened after treatment with 49% of patients reporting an erection never sufficient for intercourse at diagnosis increasing to 62% after 1 year and 69% after 2 years. We observed trends towards lower self‐esteem with increasingly mutilating treatment. Conclusion Pad use, nocturia and frequency of orgasm were significantly reduced after penile cancer treatment. We observed trends towards lower self‐esteem with increasingly mutilating treatment and increase in erectile dysfunction after treatment.

of the urethral orifice, which in turn may lead to a new perception of voiding and varying challenges with urine stream control and need for urinary aids.
Many treatments of penile cancer may affect penile sensibility, reduce sensible areas, introduce deformity and reduce length. Some of these changes may inflict sexual challenges on patients, and in some cases, the sum of changes caused by disease and treatment may affect quality of life. [1][2][3][4][5] Even if a cancer is perceived life-changing and body-image-altering, a number of human psychological defence mechanisms and survival instincts prevail in the dominating narrative of many patients, who mobilize remarkable coping strategies and thrive against difficult odds. 3,[6][7][8] Few studies have focused on differences at different time points in aspects of quality of life, voiding symptoms and sexual function after treatment for penile cancer. 9 Such data may be useful in the planning of cancer rehabilitation and might guide the focus and themes of the clinical follow-up.
In this study we assess quality of life, voiding and sexual function related to three different points in time: at diagnosis, after 1 year and after 2 years. We assess outcomes related to type of treatment, and we compare Danish penile cancer patients with healthy Scandinavian men. This study is among the first to focus on quality of life and sexuality in penile cancer at different time points in the clinical trajectory.

| METHODS
We conducted a questionnaire survey among Danish penile cancer patients from 1 January 2013 to 31 December 2015 in connection with inpatient treatment and outpatient follow-up. The study was prospectively designed as a two-centre, three-time point crosssectional questionnaire-based survey in penile cancer patients.
All patients were treated and followed up at the only two Danish urology departments treating penile cancer with curative intent.
Questionnaires were handed out, introduced and collected as a part of everyday clinical practice by health professionals involved in the clinical trajectory. There was no dedicated study specific organization.
We approached patients if they were newly diagnosed (Group 1) if they attended a 1-year follow-up visit in our outpatient clinics (Group 2) or if they attended a 2-year follow-up visit (Group 3) during the study period. Patients registered to have accepted participation but failing to return the questionnaire received an identical questionnaire, a pre-stamped envelope and a reminding letter per mail 1 month after inclusion. We excluded patients who failed to respond to first and second invitation to participate.
To assess response rates, we retrospectively extracted the patterns of referral to the two specialized centres treating penile cancer with a curative intent in Denmark from the Danish National Penile Cancer Database.

| Questionnaire
The questionnaire queried patients on a wide range of issues with focus on demographic data, psychological aspects of life, voiding symptoms and sexual experiences and symptoms. We developed the study specific questionnaire from a combination of validated questionnaires and a series of purpose-built single questions. We translated into Danish and adapted for penile cancer patients the validated Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) Questionnaire. 10 The SPCG-4 Questionnaire is partly based on other validated tools and two psychometric tests such as Spielberger's Trait measure from the State-Trait Anxiety Inventory 11 and the Centre for Epidemiological Studies Measure of Depression. 12 The psychological symptoms (anxiety, depressed mood), sense of well-being and quality of life were assessed on 7-point visual digital scales. We assessed the resulting penile cancer questionnaire for face validity in a pilot project with six patients. Because the pilot project only led to minor nonsignificant changes to the original questionnaire, we included these six patients in the study cohort. We considered responders sexually active if they had engaged in any form of sexual stimulation or intercourse 6 months prior to responding to the questionnaire.

| Comparison
We compared score prevalence between groups of penile cancer patients according to time of completion of the questionnaire and according to the type of treatment received.

| Statistics
We ensured that data were discrete and independent by only considering one response per patient. In 27 patients responding more than once, we only considered their latest response. We compared age between groups by ANOVA and differences between groups of other demographic and clinical variables by nonparametric tests. For statistical analysis we used Stata Statistical Software: Release 13, TX: StataCorp.
We considered a p-value of 0.05 or less statistically significant.

| Sexological counselling
Coinciding with study initiation, we decided to offer all penile cancer patients free in-hospital post-operative sexological counselling by a specially trained nurse as a standard of care. Thus, all study participants were offered post-operative sexological counselling.

| Symptoms and distress associated with urinary functions in penile cancer patient groups
At the current group sizes, we found few differences in symptom prevalence or bother scores between penile cancer patient groups

| Symptoms and distress associated with sexual functions in penile cancer patient groups
Trends towards increasing occurrence of sexual thoughts from first (69%) to second year (80%) after diagnosis (p = 0.40) and an increase in attributing moderate or great importance to sexuality from first (29%) to second year (42%) after diagnosis (p = 0.76) did not reach statistical significance. This was also true for the trend of increasing T A B L E 1 Patient characteristics for three groups of Danish penile cancer patients responding to a validated quality of life questionnaire at diagnosis (Group 1), after 1 year (Group 2) and after 2 years or more (Group 3)      The implementation of several items from the SPCG-4 questionnaire in our penile cancer questionnaire allows us to compare our findings to a large control cohort of cancer-free Scandinavian men from the SPCG-4 study.

| DISCUSSION
We find a significant difference between the proportion of responders scoring the importance of sexuality as moderate or great There was no difference in scores for depressed mood, well-being, quality of life and sense of meaningfulness. 13 Nocturia more than twice a night was reported by 40% of penile cancer patients and 42% of the slightly older controls, p = 0.81.
In summary, as has been reported by previous penile cancer studies, we also found in the current study that both disease and treatment had negative effects on sexual aspects of life, such as reported frequency of intercourse, reported frequency of orgasm and judged importance of sexuality, which were all scored significantly lower by penile cancer patients than SPCG-4 cancer-free controls. 1,2,5,13 During the study period, only four (  study. 5 We tried to run this study along with normal outpatient activities in two busy university clinic settings without dedicated study staff. Some of our approached and non-responding patients may have been discouraged to participate due to the substantial number of items in our questionnaire. One obvious way to approach this challenge may be to markedly reduce the number of items. Future attempts to collect patient reported outcome measures should focus on fewer items and either be integrated in obligatory electronic logistic procedures connected to the outpatient clinic routine or have dedicated data collection staff (or both) to ease participation and increase response rates. Nevertheless, penile cancer is a rare disease, and in fact, this is one of the larger series published on the subject. Our cohort represents national data with responders from both treating centres in Denmark that limits selection bias. However, we do see some indirect signs of selection bias in the dataset in our counterintuitive age distribution between Groups 1, 2 and 3, where one would expect the age to increase with time after diagnosis, the distribution of responders in our study is opposite, with more young patients participating in the group 2 years after treatment. We interpret this as a selection bias of the health professionals enrolling patients for Groups 2 and 3 in the study being more likely to invite younger patients than older patients. Only few patients were recruited from Centre 2. Because we have no questionnaire from non-responders, we have no way to compare base line characteristics from patient responses, but we are able to indirectly draw some conclusions from our knowledge of the penile cancer cohort as a whole. Our responders have a higher mean age at 70.3 years, 67.4 years and 66.4 years compared with our general penile patient cohort at 66.1 years, 14 which indicates that a larger proportion of the younger patients declined to participate in the current questionnaire study. We speculate that this might have skewered our data in the direction of less dramatic differences between scores, because it is our experience from a previous single patient interview study 3 and from our daily practice that younger patients seems to worry more about consequences of disease and treatment than older patients. If we look at other baseline parameters and compare our responders to our penile cancer cohort as a whole, we find no difference in cohabitation, education level and source of income. 15 Nearly 60% of responding penile cancer patients are sexually active at diagnosis. Pad use, nocturia and frequency of orgasm were significantly reduced after penile cancer treatment. We observed trends towards lower self-esteem with increasingly mutilating treatment and decline in erectile function after treatment. Only few patients accepted our free offer of in-hospital post-operative sexological counselling. We need to improve recruitment logistics and increase response rates in future studies to further explore the patient perspective in this rare disease.