The management of regional lymph nodes is decisive for long-term patient survival. In clinically node-negative patients (cN0), micrometastatic disease occurs in about 25% of cases and is related to the local tumour stage and grade. The delay of the lymphadenectomy procedure is associated with an increased risk of failure. Also, many authors emphasize that lymphadenectomy should be performed as soon as possible after treating the primary lesion on the penis [11–13]. Nevertheless, owing to be afraid of surgical complications or the risk of overtreatment, the studies of necessity of early inguinal lymphadenectomy operated on the patients of T1G2, especially T1aG2 are still deficient.
To the best of our knowledge, vast majority of previous studies on this issue were retrospective and none randomized controlled trials was addressed or under way. Besides, various local therapies of penile cancer, relatively few or even none ILND cases to the whole cohort, not long enough follow-up time, lack of the essential information or no pathological external validation, all of which made the nature of this issue confused and may hinder to catch significant differences. In a serious of 20 patients of T1G2 from 5 different centers, Naumann et al. demonstrated the risk for lymphatic spread to be 50% [14]. These data are similar to a sub-analysis of a Dynamic Sentinel Node Biopsy (DSNB) series published by Leijte et al.[15]. Whereas, B.Schlenker et al. reported 28.9% positive lymph nodes with a cohort of 38 cases [16]. The similar result (25%) was declared in another study include only 4 patients [17]. Confusedly, some authors published no positive lymph nodes in the T1G2 subgroup in their studies [18, 19]. In a more recent research, Rodolphe Thuret et al. had studied 655 T1 patients of cN0 who only underwent primary tumor excision but not performed an eILND relying on the database of Surveillance, Epidemiology, and End Results (SEER) [20]. In that study, the 5-year caner-specific mortality of T1G2 was 10%, which was significantly higher than T1G1 (2.6%) while the 5-year other-cause mortality of T1G2 was even 27.3%, still the benefit of eILND in T1G2 was unclear. In our opinions, there were some limitations in that study. Firstly, the proportion of excisional biopsy of primary lesion was as high as 32.4%, while biopsies of penile caner may lead to the risk of under staging a T2 or T3 tumor since the deepest point of invasion, histologic grade, and risk factors like vascular invasion were reported to be incorrect in 30% − 91% of cases [21]. Additionally, as all of patients in that cohort without an eILND, their results could not compare with a series that did undergo an eILND with no caution, especially if the eILND was performed in the context of lymph node metastasis. Referring to guidelines in this subgroup, there are no North American recommendations supporting the need for an eILND, whereas the EAU SCC treatment guidelines still do recommend an eILND being necessary to these patients [20].
In our study, the partial/total penectomy and early bilateral inguinal modified lymphadenectomy ensured the most therapeutic benefits of these patients. Also, the unified primary lesion excisions guaranteed the accuracy of pathological staging. Additionally, the median number of LNs retrieved of each side was 12, more than the requested 8 removed LNs. By performing standardized lymphadenectomy, separately submitting LN packets and with a dedicated pathologist reassessing the specimen, we obtained accurate clinical and pathologic characteristics. The differences of T1aG1 and T1aG2 according to the latest guideline even could be analyzed, which hadn’t been researched before. In this cohort, the proportion of positive lymph node of T1G2 was 68.8%, which was significantly higher than T1G1 (18.9%). We further analyzed the patients of clinically node-negative patients (cN0), micro metastatic disease occurs in T1G2 was 50% but in T1G1 was 14.8%, which also reached statistical significance. According to the latest guidelines, significant differences were reached as the risk for lymphatic spread of T1aG2 was 44.4% while only one 4.5% of T1aG1 was found inguinal lymph node metastasis. In an addition, Survival Curve had been demonstrated but no statistical differences found between T1G1 and T1G2 and the same result also existed in the cohort of T1aG1 and T1aG2, all of which revealed a strong proof of eILND’s therapeutic benefit.
Up to 68.8% of patients with T1G2 and 44.4% of patients with T1aG2 definitely harbored lymph node metastasis, lymphadenectomy should be highly recommended, which was also mentioned in the EAU guidelines for this subgroup. The option of a surveillance strategy recommended by AJCC was not applicable to these patients, since the great potential risks of a definite worsening of the prognosis in case of regional recurrence far outweighed the non–life-threatening risks of lymphadenectomy. At present, modified inguinal lymphadenectomy which reduces the morbidity and preserves the therapeutic benefit compared to radical ILND has been recommended in patients who have high-risk primary penile tumours and clinically negative groins. As the sensitivity of dynamic sentinel node biopsy (DSLNB) is variable, this technology has only been extensively studied by a few large specialized European centers but failed to gain widespread implementations in outside [22, 23]. Fortunately, in the recent years, some minimally invasive technologies have emerged like laparoscopic surgery and even robot-assisted techniques are under investigation which could further reduce patient morbidity caused by lymph node dissection and better diagnose or treat those patients who will most benefit from lymphadenectomy.
There are some limitations to our study we have to acknowledge. Firstly, it was an uncontrolled, retrospective study. With unified criteria of surgery, a dedicated pathologist reassessing the specimen, relatively new incidences (all surgeries were implemented after 2002), comprehensive clinical and pathological data, we had minimized the potential flaws of a retrospective research. Secondly, a relatively small number of T1G2 patients were included in this study. Nevertheless, most of our cohort had a long followup and the stage of primary lesion and the status of lymph node metastasis were definitely clarified by routinely standard surgical procedures. To our knowledge this is the first study in the literature to specifically concentrate on the penile cancer of T1aG1 and T1aG2 in detail. Additionally, due to socioeconomic factors, the close surveillance and appropriate caveats in the patients of T1G1 SCC tumours are unavailable in our country. Bilateral inguinal modified lymphadenectomy was offered to this subgroup to achieve the most therapeutic benefits. Lastly, though the concept of T1G2 has been updated by the latest SCC guideline, owing to such low-prevalence disease, lack of enough awareness of operative methods or decision-making strategies, ambiguity and deficiency of pathological diagnosis, a number of therapy centers as far as we know still adopt earlier version of SCC guideline in our country especially in some rural areas. In view of above, we have investigated T1G2 and T1aG2 respectively and patients with this subset should be more carefully managed.