For several decades, despite better understanding in anatomy of lymphatic system and remarkable technical advancements in cancer surgery, there has been a lack of preventive and sustainable treatment strategies for common postoperative complications of lymphadenectomy.¹ Nonetheless, less lymph node surgery has been shown to provide equivalent survival in some common solid cancers, and sentinel lymph node biopsy has been commonly utilized as a staging procedure, such as for early-stage primary breast cancer and cutaneous melanoma with clinically negative nodal basin.^2,3 In addition, a therapeutic value of sentinel lymph node biopsy was recently observed in patients with cutaneous melanoma metastatic to sentinel lymph nodes, and it was even suggested that removal of positive sentinel lymph nodes via biopsy alone could eliminate the need for complete lymph node dissection.⁴

In patients with penile squamous cell carcinoma (PSCC) without clinically palpable/visible inguinal lymph nodes (cN0), the rate of micrometastasis in inguinal lymph nodes is about 25%,^5,6 which underscores the necessity for evaluation of inguinal lymph node status for staging. Currently, for patients with ≥pT1G2 PSCC with cN0 inguinal basin, a superficial (modified) inguinal lymph node dissection (ILND) and dynamic sentinel lymph node biopsy (DSNB) are recommended by European Association of Urology and the National Comprehensive Cancer Network guidelines.^7,8 Despite technical refinements in superficial ILND over time, the superficial ILND-related morbidity remained high.⁹ Any and major grade postoperative complications after superficial ILND occurred in about 45% and 30% of the patients, respectively. Common complications included wound infection (15%), wound dehiscence/necrosis (12%), lymphedema (12%), lymphocele, hematoma and thromboembolism (4% each).

The value of sentinel lymph node biopsy for diagnostic staging of cN0 PSCC has been underexamined compared to other common solid cancers. Nonetheless, with recent refinements in the technique, DSNB was found to provide remarkably successful outcomes in PSCC.¹⁰ A hybrid indocyanine green-^99mTc-nanocolloid was utilized for DSNB, and it provided the lowest false-negative rate (1.4% at 2 years) to date among more than 400 patients with ≥T1G2N0 disease. The hybrid indocyanine green-^99mTc-nanocolloid was injected the same day or the day before surgery as sentinel node tracer and lymphoscintigraphy was performed at 0-10, 15, and 60 min after the injection (part A of Figure). Then a single-photon emission computed tomography/computed tomography was performed completing the preoperative identification of sentinel lymph node (part B of Figure). At the time of surgery, sentinel nodes were traced using a gamma probe and a mobile gamma camera (part C of Figure), and they were visualized using fluorescence camera (part D of Figure). The reported safety outcomes from this DSNB technique were also very promising. The 30-day postoperative complications were noted in 14% of groins treated, with wound infection and lymphocele being the most common complications.¹¹ All complications after the first 30 d until 90 d were mild or moderate (grade I-II) and occurred in only 3.4% of the groins.

In order to strike a balance between minimizing morbidity and improving detection of inguinal metastasis, minimally invasive techniques were also tested in patients with cN0 PSCC. Video-endoscopic inguinal lymphadenectomy and robotic-assisted video-endoscopic inguinal lymphadenectomy have been shown to be a feasible alternative to open dissection while achieving similar oncologic outcomes.^12,13 Nonetheless, the minimally invasive ILND methods were still associated with substantial morbidity, occurring in one-third of all cases, and they were mainly lymphatic complications (about 25%).¹⁴ In another study that included 34 patients who underwent robotic-assisted video-endoscopic inguinal lymphadenectomy for cN0 PSCC, any grade complication rate was reported 75%, and incidence of lymphocele, limb edema, and surgical site infection was similar compared to the open ILND group, albeit with fewer major complications.¹⁵ These complication rates are still not ideal and remain higher than those reported in DSNB (ranging from 7% to 15% overall, and about 3% rate of lymphocele).^11,16 Although convalescence after minimally ILND appeared to be faster compared to open ILND, as well as the length of hospital stay and time for drain removal were shorter, prolonged operative time is the other drawback of minimally invasive ILND, which was significantly longer than an open ILND by at least 30 min.¹³ Open modified ILND takes about 60 min;¹⁵ however, in this regard, DSNB appears to be more advantageous as well due to its shorter operative time, which is usually less than 30 min.¹⁷ Furthermore, frozen sections of several resected lymph nodes from the second inguinal side during ILND may further add to the total operative time. Given the high operating room time costs, DSNB may potentially prove itself to be a more cost-effective staging procedure, although no comparative analysis exists.

In the U.S., utilization of DSNB has been considerably low for decades.¹⁸ According to a recent survey study, use of DSNB as the preferred diagnostic staging approach for cN0 PSCC was 5% in contrast to open and robotic-assisted ILND (60% and 26%, respectively). So far, utilization of DSNB has been mostly limited to the countries with universal and more centralized health care such as The Netherlands, Denmark, and the United Kingdom.¹⁹ For example, in The Netherlands, a northwestern European country with a population of approximately 17 million, 3 academic medical centers are receiving referrals of high-risk cN0 PSCC cases for DSNB procedure from the entire country, with Amsterdam being the main referral center. The fact remains that adoption of DSNB as a staging procedure for high-risk cN0 PSCC is a challenging process. It requires a substantial learning curve, an experienced multidisciplinary medical team, close collaboration between different medical departments, and robust infrastructure for pre- and intraoperative imaging studies.²⁰ However, given its high accuracy for detection of metastatic lymph nodes, acceptably low comorbidity, and its potential to further decrease the costs, DSNB currently remains one of the biggest opportunities to be further explored for improving treatment outcomes and changing current practice patterns in the U.S. health care system.