Evolving Penile Cancer Care: Advancement of Treatment Outcomes and Patient Well-being

This thesis focuses on optimizing outcomes for patients with penile cancer, aiming to improve both survival and (sexual) quality of life. The work consists of two main parts: the first addressing oncological outcomes and innovations in treatment, and the second focusing on patient well-being and functional recovery.
Chapter 2 evaluates the development of penile cancer care in the Netherlands over the past 30 years, including more than 3,100 patients. Although penile cancer remains rare, its age-standardized incidence has increased. The findings confirm a strong trend toward centralization, with growing numbers of referrals to expertise centers. Patients treated in these centers demonstrated significantly better survival compared with those treated in regional hospitals, emphasizing the value of specialized care for rare malignancies.
Chapters 3 to 5 focus on the sentinel node procedure. After more than a decade of clinical use, nanocolloid—a human serum albumin-based tracer—was replaced by Nanoscan due to production discontinuation. Chapter 3 demonstrates that despite minor chemical differences in ICG-binding between ICG 99mTc nanocolloid and ICG 99mTc nanoscan, no significant differences were found in sentinel node visualization or complication rates. Nanoscan is therefore a safe and effective replacement.
In Chapter 4, a systematic review of hybrid fluorescent and radioactive albumin-based tracers was conducted, summarizing 60 clinical studies encompassing over 2,000 patients across 14 tumor types, including penile cancer. These results confirm the clinical value and safety of hybrid tracer technology for sentinel node mapping.
Chapter 6 explores skip metastases (SKM), defined as metastatic lesions in the corpora cavernosa or spongiosum without direct extension from the primary tumor. SKM presence was an independent predictor of poorer cancer-specific survival. Interestingly, a proportion of SKM-positive patients showed atypical metastatic patterns, such as distant metastases without lymph node involvement. Patients with SKM and pN0 disease had survival outcomes comparable to those with advanced nodal or distant metastases, indicating the aggressive nature of SKM.
The second part focuses on quality of life and sexual well-being. Chapter 7 shows that penis-sparing surgery effectively preserves organ function and overall life quality but increases the risk of local recurrence due to narrow surgical margins (>1 mm). The long-term survival impact of these recurrences remains unclear, and data on sexual outcomes are limited.
In Chapter 8, sexual satisfaction following surgery is analyzed. Men who underwent penis-sparing procedures reported greater sexual activity and higher satisfaction than those who underwent partial or total penectomy. These findings highlight the importance of integrating functional and psychosocial aspects into treatment planning.
Chapter 9 addresses the follow-up of node-negative penile cancer patients. Late lymph node metastases were rare and usually developed within the first year after treatment. Based on these findings, a new follow-up protocol is proposed: intensive surveillance with routine groin ultrasonography during the first year, followed by less frequent examinations thereafter. The frequent occurrence of local recurrences underlines the importance of patient self-examination, which could safely reduce follow-up visits by up to 50% compared to current practice.
In conclusion, this thesis demonstrates that centralization of penile cancer care and the application of innovative diagnostic, surgical, and surveillance approaches significantly improve survival and quality of life. Future care should emphasize personalized, multidisciplinary management in which oncological outcomes and patient well-being are equally prioritized.