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 » Introduction
 » Subjects and Methods
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  Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 2  |  Page : 309-312
 

Prognostic factors and 5-year survival of patients with carcinoma penis: Tertiary health center study


1 Department of Surgical Oncology, Mahavir Cancer Sansthan, Phulwari Sharif, Patna, Bihar, India
2 Department of Pathology, Mahavir Cancer Sansthan, Phulwari Sharif, Patna, Bihar, India

Date of Web Publication6-Jan-2017

Correspondence Address:
A A Shah
Department of Surgical Oncology, Mahavir Cancer Sansthan, Phulwari Sharif, Patna, Bihar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.197729

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 » Abstract 

Context: To identify prognostic factors in carcinoma penis with its impact on survival. Aims: To find out the relation of various prognostic factors of carcinoma penis with the various outcomes. Settings and Design: Retrospective cohort study. Subjects and Methods: Each patient diagnosed as having carcinoma of penis by incision biopsy and operated from January 2004 to May 2009 at the institute was included in the study (n = 117). Data were collected and analyzed. Statistical Analysis Used: The Chi-square (χ2) test was used to test for the significance of association between the independent (predictor) and dependent (outcome) variables. Multivariate logistic regression analysis was used to determine predictor variables that predicted the outcome. Five year disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Results: Of the total 117 patients studied, 30 patients died within 5 years (median = 25 months). Recurrences (local or systemic) were seen in 23 patients (median = 14 months). Five-year DFS was 80.34% and OS was 72.22%. Kaplan–Meier analysis showed that well to moderately differentiated grade, lymph node negative disease and low stage have higher survivals than poorly differentiated grade, lymph node positive disease and higher stage, respectively. Multiple logistic regression analysis revealed that inguinal lymph node positivity and grade were significantly associated with local or systemic recurrence. Conclusions: Penile cancer patients with advanced disease had poor survival. Tumor grade and inguinal lymph node metastasis are factors affecting DFS. Lymphadenectomy remains an integral part of the management of patients with penile cancer.


Keywords: Carcinoma penis, lymph node, metastasis, penile cancer, prognosis, survival


How to cite this article:
Shah A A, Shah H A, Panjwani G N, Pandey B B, Shah N. Prognostic factors and 5-year survival of patients with carcinoma penis: Tertiary health center study. Indian J Cancer 2016;53:309-12

How to cite this URL:
Shah A A, Shah H A, Panjwani G N, Pandey B B, Shah N. Prognostic factors and 5-year survival of patients with carcinoma penis: Tertiary health center study. Indian J Cancer [serial online] 2016 [cited 2019 Aug 19];53:309-12. Available from: http://www.indianjcancer.com/text.asp?2016/53/2/309/197729



 » Introduction Top


Cancers of the penis are rare in the United States, Europe, and other industrialized countries, but are more common in less developed areas of the world, such as parts of Africa, Asia, and South America. In the United States, penile carcinoma accounts for <1% of cancers in men, with <2000 new cases and 300 deaths annually.[1] However, in parts of Africa, Asia, and South America, penile cancer accounts for approximately 10–20% of all malignancies in men.[2] Penile cancer is typically a disease of older men and rates increase steadily with age.[3] The mean age at diagnosis is 60 years, although penile cancer is seen in men <40 years.[4],[5] Without treatment, patients with penile squamous cell carcinoma (SCC) usually die within 2 years after diagnosis of the primary lesion because of uncontrollable locoregional disease or from distant metastases. Tumor stage, grade, and spread of the tumor to the regional lymph nodes (lymph node positivity) is the most relevant prognostic factor.[6],[7]

The major issue in penile cancer is deciding whether patient should undergo lymph node dissection as false positive and false negative results of the clinical examination or radiological findings are high with respect to metastatic nodal disease.[8],[9] Inguinal and iliac lymph node dissection should be considered for its effectiveness versus short- and long-term morbidity. The aim of this study is to find out the relation between various prognostic factors of carcinoma penis with multiple outcome parameters after at least 5 years.


 » Subjects and Methods Top


Study design

Retrospective observational study.

Inclusion criteria

  • Each patient who was diagnosed as having carcinoma of penis by incision biopsy and operated from January 2004 to May 2009 at the institute.


Exclusion criteria

  • Nonavailability of medical records, investigation records, history sheets of diagnosed patients of any age group
  • Patients with fixed inguinal lymph nodes or inoperable disease at presentation.


Methodology

One hundred and thirty consecutive patients of penile carcinoma diagnosed by incision biopsy and primarily treated by surgery from January 2004 to May 2009 were included in the study. Patients were thoroughly examined clinically for penile growth and inguinal region for regional nodal enlargement. Apart from routine blood investigation, chest X-ray and ultrasound abdomen were done to rule out any systemic metastasis. Computed tomography scan of abdomen and pelvis was performed in clinically enlarged inguinal nodes to look for pelvic nodal enlargement. Patients were categorized as per the American Joint Committee on Cancer tumor-node-metastasis staging for penile cancer (6th ed., 2003). All patients after proper examination and work-up were called in the multidisciplinary tumor board and final management decision was taken. All patients with Ta or T1 primary with Grade I disease were treated with surgery without inguinal lymph node dissection (ILND). Patients having inguinal lymph nodes >4 cm or fixed to underlying structures or having enlarged pelvic nodes or inoperable primary disease were sent for neo-adjuvant chemotherapy and they were excluded from the study. Patients with T2 or higher primary disease and T1 with Grade II or III were treated by partial penectomy or total penectomy (according to the involvement of penis or prepuce) with ILND. Due to nonavailability of frozen section in many hospitals in developing countries such as ours, specimen of the ILND was completely evaluated by palpation by surgical oncologist and pelvic lymph node dissection (PLND) (includes iliac and obturator group) of the same side of the suspicious inguinal node was carried out on the same sitting. A standard full template ILND was performed with preservation of saphenous vein. All PLND were done by separate lower abdominal incision with extraperitoneal approach. Adjuvant radiotherapy was given to inguinal and pelvic region in case of positive nodes and adjuvant chemotherapy was added in case of bilateral (B/L) positive inguinal nodes or positive pelvic nodes. Patients were kept in follow-up, 6 monthly in the first 3 years and then yearly for the next 2 years. On each visit, clinical locoregional examination and ultrasound of abdomen and chest X-ray were done to look for any systemic failure. Data were collected by review of records for the age of the patient, clinical presentation, tumor stage, histopathological type and grade, the presence of lymph node or distant metastases, treatment modalities, surgical complications, and compliance to adjuvant treatment and follow-up. Tumor grading was done in three-tier system as described by Maiche et al.[10] Disease-free survival (DFS) was defined as the length of time from the date of surgery to any tumor-related relapse. Overall survival (OS) was determined as the time from surgery until the date of death. This study pro forma was presented to the Institutional Ethical Committee and approved.

Statistical analysis

The statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 17.0 (International Business Machine Corporation, Armonk, New York, U.S) for Windows. The median and ranges were calculated for continuous variables, whereas proportions and frequency tables were used to summarize categorical variables. The Chi-square (χ2) test was used to test for the significance of the association between the independent (predictor) and dependent (outcome) variables in the categorical variables. The level of significance was considered as P < 0.05. Multivariate logistic regression analysis was used to determine predictor variables that predicted the outcome. Five-year DFS and OS were calculated using the Kaplan–Meier method.


 » Results Top


During the study, 130 patients of carcinoma of penis diagnosed by incision biopsy were registered in the institutional registry. Due to lack of data, 13 patients were excluded from the study and 117 patients were included in the study. The age of patients at diagnosis ranged from 20 to 84 years with the median age of 51 years [Table 1]. The peak incidence was in the age group of 51–60 years. Eighty-five (72.64%) patients belonged to 41–70 years of age. Of the type of surgical procedures performed, partial penectomy and B/L ILND was the most frequently performed surgical procedure, accounting for 66.66% of cases [Table 2]. Keratinizing SCC was the most common histology (90.59%). Rest were nonkeratinizing SCC (4.27%), verrucous carcinoma (4.27%), and sarcomatoid SCC (0.85%). Fifty-eight (49.57%), 54 (46.15%), and 5 (4.27%) patients had Grade II, III, and I disease, respectively [Table 3]. Seventy-two (61.53%) patients presented in Stage 2 [Table 4].
Table 1: Age-wise distribution of carcinoma of penis

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Table 2: Different types of surgical treatment offered

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Table 3: Number of patients with different grades of tumor

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Table 4: Tumor, node, metastasis stage-wise presentation

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Inguinal lymph nodes metastases were seen in 28 patients (23.93%) and iliac lymph node metastases in five patients. No skip metastasis to direct iliac nodes was observed, but iliac node positivity was seen in 17.85% of patients with positive inguinal metastasis. The sensitivity of clinical intra-operative assessment of harboring metastasis in inguinal lymph node came out to be 50% only but the acceptable specificity of 87.95% [Table 5]. Fourteen patients required second stage operation for PLND. Postoperative complications are shown in [Table 6]. All complications such as marginal skin necrosis, seroma formation, wound infection, and lymphedema (P = 0.0215) were more common in ILND + PLND.
Table 5: Intra-operative clinical assessment and final histopathology report

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Table 6: Postoperative complications

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Thirty patients died within 5 years (median = 25 months). Recurrences (local or systemic) were seen in 23 (19.65%) (median = 14 months). There were three local, two locoregional, eight regional (Inguinal or pelvic), two locoregional + systemic and ten distant metastasis. Out of systemic failures, most common were in lung followed by liver. Five-year DFS for all stages was found to be 80.34% and OS was 72.22%. Five year OS for Stage I and II (lymph node negative disease) was 95.55% and for Stage III and IV (lymph node positive) was 46.55%. Twenty-one patients defaulted for adjuvant treatment and out of them 15 (62.5%) patients developed recurrence. Kaplan–Meier survival analysis showed that inguinal lymph node negative disease, pelvic lymph node negative disease and patients who were adherent to adjuvant treatment have higher DFS than patients with inguinal lymph node positive disease [Figure 1]a, pelvic lymph node positive disease and those who defaulted for adjuvant treatment, respectively. As grade [Figure 2]a and stage increase DFS decreases. Multiple logistic regression analysis revealed that inguinal lymph node positivity (P = 0.013) and grade (P = 0.002) were significantly associated with recurrence. Kaplan–Meier survival analysis also showed that inguinal lymph node positivity and grade were significantly associated with OS [Figure 1]b and [Figure 2]b. Bivariate analysis revealed significantly higher rate of recurrence in patients with higher grade (P < 0.0001), inguinal node positivity (P < 0.0001), iliac node positivity (P < 0.0001), higher stage (P < 0.0001) and those who defaulted to adjuvant treatment (P = 0.0163).
Figure 1: (a) Kaplan–Meier disease free survival curve for inguinal lymphnode positive and negative disease. (b) Kaplan–Meier overall survival curve for inguinal lymphnode positive and negative disease

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Figure 2: (a) Kaplan–Meier disease free survival curve for grade of tumor. (b) Kaplan–Meier overall survival curve for grade of tumor

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 » Discussion Top


Cancer of the penis, although rare in developed countries, constitutes a continuing challenge to health-care provider. Penile cancer is typically a disease of older men and rates increase steadily with age.[11] Many studies in developed countries indicate a higher incidence of the disease between the sixth and seventh decades of life.[5],[11] The median age of 51 years found in our study co-incides with the literature. About 47% of patients were found in fifth and sixth decade, but 25.64% of patients also found in fourth decade suggesting rising incidence in young population. Partial penectomy with B/L ILND remains the most commonly performed surgical procedure as 61.53% of patients presented with Stage 2. Totally 28 patients required adjuvant treatment, out of them 18 defaulted. Of these 18 patients, recurrence was seen in 13 patients suggesting the need and importance of adjuvant therapy (P = 0.0163).

In a large series described by Graafland et al. reported inguinal lymph node metastasis in 37% of patients and pelvic lymph node metastasis occurred in 19–48% of all node positive patients.[6],[12] In our series, inguinal lymph nodes metastases were seen in 28 patients (23.93%) and pelvic node metastasis in 5 patients, which consists of 17.85% of patients with positive inguinal metastasis. Fourteen patients required second stage procedure due to lack of sensitivity of clinical plus radiological plus intraoperative clinical examination. Frozen section is definitive answer of this situation but in developing countries, low resource institutes like ours without frozen section are still suffering from this issue. Prophylactic PLND in all patients is another approach to deal with this situation, but it leads to overtreatment in 73 patients in our series which increases the complications as described in [Table 3]. Postoperative complications in our series were also similar as described in the literature.[8],[13]

Thirty patients in our study died within 5 years (median = 25 months). Guimarães et al. reported 24% recurrence rate.[14] Recurrences (local or systemic) were seen in 23 patients (19.65%) (median = 14 months) in the study. Five year DFS was found to be 80.34% and OS was found to be 72.22%. Different series reported 5 year OS for Stage I and II ranging from 74% to 93% and for Stage III and IV ranging from 28% to 50%.[15],[16] In this study, 5 year OS for Stage I and II was 95.55% and for Stage III and IV was 46.55% which coincides with the literature. Out of 54 patients who had Grade I tumor, recurrence was seen in only 1 patient. However, out of 58 patients who had Grade II tumor, recurrences were seen in 18 patients and out of five patients with Grade III tumor, recurrences were seen in four patients suggesting that as grade increases, recurrence rate increases (P < 0.0001). Multiple logistic regression analysis revealed that inguinal lymph node positivity (P = 0.0274) and grade (P = 0.0074) were significantly associated with recurrence which again correlates with literature showing inguinal node positivity as the most important prognostic factor.[12] To the best of our knowledge, grade proving to be a significant prognostic factor in multivariate analysis is a new finding. None of the patients having pelvic lymph node metastases lived for 5 years, which is again a consistent finding found in many studies.[17],[18],[19]


 » Conclusions Top


Penile cancer patients with advanced disease had poor survival. Tumor grade and inguinal lymph node metastasis are factors affecting DFS. Lymphadenectomy remains an integral part of the management of patients with penile cancer.

Limitation of study

As our histopathology report was not mentioning lymphovascular invasion, perineural invasion and extranodal spread, we were unable to consider these variables in the final outcomes in spite of knowing that there are evidences as these factors have some prognostic significance.

Acknowledgment

We are thankful to our operation theater staff and record room staff for their cooperation.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5-29.  Back to cited text no. 1
    
2.
Ornellas AA. Management of penile cancer. J Surg Oncol 2008;97:199-200.  Back to cited text no. 2
    
3.
Hernandez BY, Barnholtz-Sloan J, German RR, Giuliano A, Goodman MT, King JB, et al. Burden of invasive squamous cell carcinoma of the penis in the United States, 1998-2003. Cancer 2008;113 10 Suppl: 2883-91.  Back to cited text no. 3
    
4.
Hegarty PK, Kayes O, Freeman A, Christopher N, Ralph DJ, Minhas S. A prospective study of 100 cases of penile cancer managed according to European Association of Urology guidelines. BJU Int 2006;98:526-31.  Back to cited text no. 4
    
5.
Favorito LA, Nardi AC, Ronalsa M, Zequi SC, Sampaio FJ, Glina S. Epidemiologic study on penile cancer in Brazil. Int Braz J Urol 2008;34:587-91.  Back to cited text no. 5
    
6.
Graafland NM, Verhoeven RH, Coebergh JW, Horenblas S. Incidence trends and survival of penile squamous cell carcinoma in the Netherlands. Int J Cancer 2011;128:426-32.  Back to cited text no. 6
    
7.
Novara G, Galfano A, De Marco V, Artibani W, Ficarra V. Prognostic factors in squamous cell carcinoma of the penis. Nat Clin Pract Urol 2007;4:140-6.  Back to cited text no. 7
    
8.
Ornellas AA, Seixas AL, Marota A, Wisnescky A, Campos F, de Moraes JR. Surgical treatment of invasive squamous cell carcinoma of the penis: Retrospective analysis of 350 cases. J Urol 1994;151:1244-9.  Back to cited text no. 8
    
9.
Ravi R. Correlation between the extent of nodal involvement and survival following groin dissection for carcinoma of the penis. Br J Urol 1993;72(5 Pt 2):817-9.  Back to cited text no. 9
    
10.
Maiche AG, Pyrhönen S, Karkinen M. Histological grading of squamous cell carcinoma of the penis: A new scoring system. Br J Urol 1991;67:522-6.  Back to cited text no. 10
    
11.
Magoha G, Ngumi Z. Cancer of the penis at Kenyatta National Hospital. East Afr Med J 2000;77:526-30.  Back to cited text no. 11
    
12.
Zhu Y, Ye DW. Lymph node metastases and prognosis in penile cancer. Chin J Cancer Res 2012;24:90-6.  Back to cited text no. 12
    
13.
Ravi R. Prophylactic lymphadenectomy vs observation vs inguinal biopsy in node-negative patients with invasive carcinoma of the penis. Jpn J Clin Oncol 1993;23:53-8.  Back to cited text no. 13
    
14.
Guimarães GC, Cunha IW, Soares FA, Lopes A, Torres J, Chaux A, et al. Penile squamous cell carcinoma clinicopathological features, nodal metastasis and outcome in 333 cases. J Urol 2009;182:528-34.  Back to cited text no. 14
    
15.
Srinivas V, Morse MJ, Herr HW, Sogani PC, Whitmore WF Jr. Penile cancer: Relation of extent of nodal metastasis to survival. J Urol 1987;137:880-2.  Back to cited text no. 15
    
16.
Horenblas S, van Tinteren H. Squamous cell carcinoma of the penis. IV. Prognostic factors of survival: Analysis of tumor, nodes and metastasis classification system. J Urol 1994;151:1239-43.  Back to cited text no. 16
    
17.
Lont AP, Kroon BK, Gallee MP, van Tinteren H, Moonen LM, Horenblas S. Pelvic lymph node dissection for penile carcinoma: Extent of inguinal lymph node involvement as an indicator for pelvic lymph node involvement and survival. J Urol 2007;177:947-52.  Back to cited text no. 17
    
18.
Pandey D, Mahajan V, Kannan RR. Prognostic factors in node-positive carcinoma of the penis. J Surg Oncol 2006;93:133-8.  Back to cited text no. 18
    
19.
Ficarra V, Akduman B, Bouchot O, Palou J, Tobias-Machado M. Prognostic factors in penile cancer. Urology 2010;76 2 Supl 1:S66-73.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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