Inguinal Lymphadenectomy for Penile Cancer: an Interim Report From a Prospective Randomized Clinical Trial Comparing Open vs. Video-endoscopic Approach
Phase: NA
Conditions: Penile Cancer, Lymph Node Metastasis, Sentinel Lymph Node, Surgical Complication
Sponsor: A.O.U. Città della Salute e della Scienza

  
  
 
                                  Study protocol  
 
Project title:   
 
  
 
Surgical  and oncological  outcomes  of  the  laparoscopic  assisted  radical  
inguinal  
 
lymphoadenectomy  for  cN1/N2  penile  cancer:  a  prospective  comparative  
study  between  
 
open and laparoscopic approach  
 
Local Ethics Committee Approval n° 00025/2020 of date April 4, 2020 
 
Date: March 31, 2020  
 
  
 
Principal  Investigator: Marco  Falcone MD,  Urologist,  SC  UROLOGIA  
Presidio  
 
Molinette – Città della Salute e della Scienza di Torino  
 
  
 
Background and aims:   
 

  
 
Penile  cancer represents,  to  date, a  rare  oncological  pathology  (1/100000  
males  in  
 
Europe).  However,  in tertiary  reference  centres,  such  as  the  SCU  Urologia  
(Prof. P.  
 
Gontero), the number of patients sent for this pathology is increasing.   
 
Although for the  main  lesion  (T)  there  are  now  consolidated  standards  of  
care,  
 
increasingly  aimed  at  a conservative  "sexual  sparing"  approach where  
oncologically  
 
possible,  the  management  of  loco-regional lymph  nodes is  still not  completely  
 
standardized.  
 
The European Guidelines (EAU) recommend bilateral inguinal radical 
lymphadenectomy  
 
for cN1/N2 (palpable lymph nodes mono/bilaterally, but not fixed) or high-risk 
tumour (>  
 
T1G2).  
 
Lymph  node  management  is the factor  that most influences patient  survival. For  
this  
 
reason, this must be entrusted to highly specialized centres. Some recent trials have 
shown  
 
that  bilateral  inguinal lymphadenectomy  has  a  statistically  significant  
superiority  to  
 
radiotherapy and clinical surveillance in cN1/N2 patients.  
 
Despite  this, inguinal  lymphadenectomy has an  important  incidence  of  
morbidity  (up  to  
 

50% of cases) which often wrongly limits its indications.   
 
Main complications are:  
 
 - Lymphocele  
 
- Prolonged lymphatic drainage  
 
- Skin necrosis  
 
- Dehiscence of the surgical wound  
 
- Edema of lower limbs and genitals  
 
  
 
Only few studies have recently evaluated the oncological and functional results of 
inguinal  
 
lymphadenectomy  performed  with  minimally  invasive  techniques  using  video- 
 
laparoscopic instruments. First results seem to support minimally invasive 
approach, that  
 
appears to have comparable oncological results and less post-operative morbidity.  
 
However, evidences are still extremely limited, and no high-grade 
recommendations can  
 
be made.  
 
  
 
The aim  of  the present  study is  to prospectively compare oncological  and  
functional  
 
results of penile radical inguinal lymphadenectomy performed with an open versus 
video- 
 
laparoscopic technique.  
 
  
 

Study design:  
 
  
 
Surgical, observational, prospective, monocentric study.  
 
20  patients with  indication  for  inguinal  lymphadenectomy  (according  to  EAU  
2019  
 
Guidelines - in case of primary lesion > pT1G2 or in case of lymph node disease 
cN1/N2)  
 
will be enrolled.   
 
Each  patient  will  undergo  treatment  of the  primary  lesion  and  contextual  
inguinal  
 
lymphadenectomy. The procedure will be performed in this way:  
 
- Groin 1: open lymphadenectomy performed by a surgical team with extensive 
experience  
 
in traditional surgery  
 
- Groin  2:  laparoscopic  lymphadenectomy performed  by  a  surgical  team  with  
extensive  
 
experience in minimally invasive surgery  
 
The results of these procedures will be prospectively collected and compared.  
 
The  main  outcome will be  the  percentage  of  postoperative  complications 
(lymphocele,  
 
prolonged lymph drainage, necrosis of the skin, dehiscence of the surgical wound, 
edema  
 
of lower  limb,  emergency  admission from the  ED,  re-intervention/surgical  
revision).  
 
Complications  will be classified  according  to  the  international  Clavien-Dindo  
 

classification.   
 
Additionally,  secondary  outcomes (number  of  lymph  nodes,  number  of  
positive  lymph  
 
nodes, surgical time) will be evaluated.  
 
After the operation, patients will attend a 24-month follow-up program, as reported 
in the  
 
flow chart, functional results and patient satisfaction will be evaluated during the 
visits.  
 
  
 
Statistical analysis:  
 
The categorical variables will be described using frequency and percentage, and 
the  
 
continuous variables will be described using median and interquartile range (IQR) 
value.  
 
Differences between groups will be assessed by the Student independent t test or 
the  
 
Mann-Whitney U test on the basis of their normal or not-normal distribution, 
respectively  
 
(normality of variables’ distribution will be tested by the Kolmogorov-Smirnov 
test).  
 
                                        Pag. 2 di 5 

  
 
Inclusion Criteria:  
 
Age  of  patients  [45-80],  CCI  ≤  3.  Penile  tumour  with inguinal  
lymphadenectomy  
 
indication, according to EAU 2019 guidelines. Written informed consent.  
 
  
 
Exclusion Criteria:  
 
Age of patients> 80, CCI ≥ 3. Patients with lymphatic disorders of lower limbs. 
Patients  
 
with  previous inguinal surgery/radiotherapy.  Previous  or  concomitant  diagnosis  
of  other  
 
tumours.  
  
 
Study Endpoints  
 
  
 
Primary endpoint:   
 
- Compare peri/postoperative complications  of  open VS  video-laparoscopic  
 
lymphadenectomy  
  
 
Secondary endpoint:  
 
- Compare surgical time of procedures, number of lymph nodes removed, number  
 
of metastatic lymph nodes   
 
  
 
Outcomes measures:  
 

  
 
Complications: lymphocele,  prolonged  lymph  drainage,  necrosis  of  the  
skin,  
 
dehiscence  of  the  surgical  wound, edema  of lower  limb,  emergency  admission  
from  
 
the ED, surgical re-operation/revision. Stratification of complications according to 
the  
 
international classification of Clavien-Dindo.  
  
 
Secondary outcomes evaluation: surgical  time  of the procedures, number of 
lymph  
 
nodes removed, number of lymph nodes that are metastatic.  
  
 
Video – laparoscopic procedure learning curve analysis  
  
 
  
 
Study planning:  
 
Kick off of the project: April 2029  
 
Expected date deadline: April 2023  
 
  
 
Duration  of  the  study  (referring  to  the  individual  patient  and  including  all  
phases: recruitment, treatment, follow-up): 24 months.  
 
 
Statistical Analysis: 
 
Continuos data were analysed using analysis of covariance and categorical data 
were compared using a chi2 test . 
 
 

Bibliography  
 
  
 
[1] Kieffer JM, Djajadiningrat RS, van Muilekom EAM, Graafland NM, Horenblas S, Aaronson 
NK.  
Quality of Life for Patients Treated for Penile Cancer. J Urol 2014;192:1105–10.  
doi:10.1016/j.juro.2014.04.014.  
 
[2] Misra S, Chaturvedi A, Misra NC. Penile carcinoma: a challenge for the developing world. 
Lancet  
Oncol 2004;5:240–7. doi:10.1016/S1470-2045(04)01427-5.  
 
[3] Barnholtz-Sloan JS, Maldonado JL, Pow-sang J, Giuliano AR, Guiliano AR. Incidence trends 
in  
primary malignant penile cancer. Urol Oncol 2007;25:361–7. doi:10.1016/j.urolonc.2006.08.029.  
 
[4] Hegarty PK, Shabbir M, Hughes B, Minhas S, Perry M, Watkin N, et al. Penile preserving 
surgery  
and surgical strategies to maximize penile form and function in penile cancer: recommendations  
from the United Kingdom experience. World J Urol 2009;27:179–87. doi:10.1007/s00345-008- 
0312-x.  
 
[5] Minhas S, Kayes O, Hegarty P, Kumar P, Freeman A, Ralph D. What surgical resection 
margins  
are required to achieve oncological control in men with primary penile cancer? BJU Int  
2005;96:1040–3. doi:10.1111/j.1464-410X.2005.05769.x.  
 
[6] Albersen M, Ph D, Parnham A, Ch MBB, Urol FRCS, Joniau S, et al. Predictive factors for 
local  
recurrence after glansectomy and neoglans reconstruction for penile squamous cell carcinoma.  
Urol Oncol Semin Orig Investig 2018;36:141–6. doi:10.1016/j.urolonc.2017.07.025.  
 
[7] Sedigh O, Falcone M, Ceruti C, Timpano M, Preto M, Oderda M, et al. Sexual function after  
surgical treatment for penile cancer: which organ sparing approach gives the best results? Can 
Urol  
Assoc J 2015;9:E423-7. doi:10.5489/cuaj.2801.  
 
[8] Hakenberg OW, Compérat EM, Minhas S, Necchi A, Protzel C, Watkin N. EAU guidelines 
on  
penile cancer: 2014 update. Eur Urol 2015;67:142–50. doi:10.1016/j.eururo.2014.10.017.  
 
[9] Kumar V, Sethia KK. Prospective study comparing video-endoscopic radical inguinal lymph 
node  
dissection (VEILND) with open radical ILND (OILND) for penile cancer over an 8-year period.  
BJU Int 2017;119:530–4. doi:10.1111/bju.13660.