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Ca penis

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Joydeep Ghosh
Joydeep Ghosh

This document summarizes risk factors, staging, and management recommendations for carcinoma of the penis. It discusses that chronic inflammation, phimosis, smoking, HPV infection, and multiple sexual partners increase risk. Staging involves physical exam, MRI, CT, and PET imaging. Early stage disease is treated with surgery or radiation, while advanced disease may receive neoadjuvant chemotherapy followed by surgery or radiation. Lymph node involvement is managed with lymph node dissection or surveillance. Recurrence is treated with chemotherapy, which has shown response rates of 30-50% in trials combining agents like cisplatin and taxanes. Targeted therapies like cetuximab may also have efficacy in advanced disease.

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Carcinoma penis Joydeep Ghosh SR, medical oncology
Risk factors.. Risk factor Relevance Phimosis OR 11-16 chronic penile inflammation (balanoposthitis related to phimosis) balanitis xerotica obliterans (lichen sclerosus) Increased risk sporalene and UV-A phototherapy for various dermatologic conditions such as psoriasis Incidence increases 9 folds with > 250 treatments Smoking 5 fold increase HPV infection, esp types 16 and 18 Present in 22 68% cases Rural area, low SE status, unmarried Multiple sexual partners, early age if intercourse 3-5 fold increased risk
Ca penis
Ca penis
Ca penis
N: 193 Included the following: Histological grade Depth of infiltration PNI Score: 0: no mets, 7: 80% mets May be used as a guide to inguinal node dissection
Recommendations for staging Primary tumor Physical examination, recording morphology, extent and invasion of penile structures. MRI with artificial erection in selected cases with intended organ preserving surgery. Inguinal nodes: Physical examination of both groins, recording number, laterality and characteristics of inguinal nodes If nodes are not palpable, invasive lymph node staging in high-risk patients. If nodes are palpable, a pelvic CT may be indicated, PET/CT is an option. Distant mets In N+ patients, abdomino-pelvic CT scan and chest X-ray are required for systemic staging. PET/CT scan is an option. Bone scan if clinically indicated
Stage wise management Tis Topical 5FU Laser ablation Resurfacing of glans Ta, T1a Wide excision Laser Glansectomy EBRT or brachyRx
T2 with corpora cavernosa invasion Partial amputation RT for lesions <4cm T3 with urethral involvement Partial or total penectomy with perineal urethrostomy T4 lesion: NACT followed by surgery in responders Pall EBRT
Management of regional nodes Defn of regional nodes:
cN0 nodes: Surveillance: only for very early lesions, pTa, pTis Invasive nodal lesions: Modified ILND SLNB : Tc99 colloid or patent blue, sensi: 88-90% If LN are found to be positive: ipsilateral ILND is indicated
Palpable inguinal nodes: cN1, cN2 Antibiotics and reassessment: NOT RECOMMENDED no additional investigation is required if palpable clinically However, CT/ MRI/ PET may be used to rule out pelvis LN Options: Ipsilateral ILND Pelvis LND If two or more positive lymph nodes or Ornellas AA,. J Surg Oncol 2008 May one node with extracapsular extension (pN3) Lughezzani G,. J Urol 2013 Nov
Fixed nodes Metastatic workup is necessary Surgery is not generally recommended Multimodal treatment is recommended NACT followed by surgery in responders Long term survival of 30% Pizzocaro G, Piva L. Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol 1988;27(6b):823-4
Nodal recurrence If after surveillance: same principles apply as before If after LND Mets w/u NACT or ACT after re surgery if feasible
Role of RT Not much published data Does not improve survival either in neoadjuvant or adjuvant settings Prospective trial comparing RT vs surgery: surgery better Kulkarni JN, Kamat MR. et al Eur Urol 1994 Adjuvant chemo is better than adjuvant RT: retrospective data Lucky MA, Rogers B, Parr NJ. Referrals into a dedicated British penile cancer centre and sources of possible delay. Sex Transm Infect 2009
Role of chemotherapy Adjuvant: Italian group: 1979-1990 25 pts treated with weekly VMB (VCR, bleomycin, mtx): for 12 couses Compared to retrospective cohort of 35pts Median f/u 42 months Long term DFS: 84% vs 39%
N: 19 pts Median f/u: 15.3 months Median DFS was 16.2 months Median OS was not reached
No data available on adjuvant in pN1 disease
NACT for fixed or relapsed nodes Small retrospective studies of 5-20 patients have reported bleomycin-vincristine- methotrexate (BVM) and bleomycin- methotrexate-cisplatin (BMP) Hakenberg OW, Nippgen JB, Froehner M, et al. Cisplatin, methotrexate and bleomycin for treating advanced penile carcinoma. BJU Int 2006 Leijte JA, Kerst JM, Bais E, et al. Neoadjuvant chemotherapy in advanced penile carcinoma. Eur Urol 2007
N : 28 irinotecan (60 mg/m2) on days 1, 8 and 15 and cisplatin (80mg/m2) administered every 28 days T3/4, N1-3, M1 were included Failed to demonstrate a response rate of more than 30%
N: 30 N2/3 disease, non metastatic ORR: 50% Median f/u 34 months 30% remained alive and disease free TTP and OS was significantly associated with Response Absence of bilateral residual tumor Absence of PNE
N : 29 Locally advanced or metastatic Doce: 75mg/m2 d1, CDDP: 60mg/m2 d1, 5FU: 750mg/m2 day1-5 Primary outcome: objective response OR: 38.5% Grade 3/4 toxicity: 65.5%
Advanced metastatic and relapsed disease Palliative chemotherapy Initial studies showed response to cisplatin Recent studies have shown even better response on addition of taxanes Virtually no data on second lien therapy Upcoming data on EGFR blockade Cetuximab, panitumumab
Studies in the metastatic settings
N: 25 Single agent paclitaxel 175mg/m2 q 3 wks PR: 20% Median PFS: 11wks Median survival 32 weeks
Retrospective anaysis N: 26 Taxane with platinum Median PSF: 96days (approx: 13wks) Median OS: 246 days (approx: 35wks)
Case reports 2 cases Prolonged survival
Place of targeted therapies Retrospective 13 pts Median PFS: 3.2mo Median OS: 9.8mo
Effect of panitumumab
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Ca penis

  • 2. Risk factors.. Risk factor Relevance Phimosis OR 11-16 chronic penile inflammation (balanoposthitis related to phimosis) balanitis xerotica obliterans (lichen sclerosus) Increased risk sporalene and UV-A phototherapy for various dermatologic conditions such as psoriasis Incidence increases 9 folds with > 250 treatments Smoking 5 fold increase HPV infection, esp types 16 and 18 Present in 22 68% cases Rural area, low SE status, unmarried Multiple sexual partners, early age if intercourse 3-5 fold increased risk
  • 6. N: 193 Included the following: Histological grade Depth of infiltration PNI Score: 0: no mets, 7: 80% mets May be used as a guide to inguinal node dissection
  • 7. Recommendations for staging Primary tumor Physical examination, recording morphology, extent and invasion of penile structures. MRI with artificial erection in selected cases with intended organ preserving surgery. Inguinal nodes: Physical examination of both groins, recording number, laterality and characteristics of inguinal nodes If nodes are not palpable, invasive lymph node staging in high-risk patients. If nodes are palpable, a pelvic CT may be indicated, PET/CT is an option. Distant mets In N+ patients, abdomino-pelvic CT scan and chest X-ray are required for systemic staging. PET/CT scan is an option. Bone scan if clinically indicated
  • 8. Stage wise management Tis Topical 5FU Laser ablation Resurfacing of glans Ta, T1a Wide excision Laser Glansectomy EBRT or brachyRx
  • 9. T2 with corpora cavernosa invasion Partial amputation RT for lesions <4cm T3 with urethral involvement Partial or total penectomy with perineal urethrostomy T4 lesion: NACT followed by surgery in responders Pall EBRT
  • 10. Management of regional nodes Defn of regional nodes:
  • 11. cN0 nodes: Surveillance: only for very early lesions, pTa, pTis Invasive nodal lesions: Modified ILND SLNB : Tc99 colloid or patent blue, sensi: 88-90% If LN are found to be positive: ipsilateral ILND is indicated
  • 12. Palpable inguinal nodes: cN1, cN2 Antibiotics and reassessment: NOT RECOMMENDED no additional investigation is required if palpable clinically However, CT/ MRI/ PET may be used to rule out pelvis LN Options: Ipsilateral ILND Pelvis LND If two or more positive lymph nodes or Ornellas AA,. J Surg Oncol 2008 May one node with extracapsular extension (pN3) Lughezzani G,. J Urol 2013 Nov
  • 13. Fixed nodes Metastatic workup is necessary Surgery is not generally recommended Multimodal treatment is recommended NACT followed by surgery in responders Long term survival of 30% Pizzocaro G, Piva L. Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol 1988;27(6b):823-4
  • 14. Nodal recurrence If after surveillance: same principles apply as before If after LND Mets w/u NACT or ACT after re surgery if feasible
  • 15. Role of RT Not much published data Does not improve survival either in neoadjuvant or adjuvant settings Prospective trial comparing RT vs surgery: surgery better Kulkarni JN, Kamat MR. et al Eur Urol 1994 Adjuvant chemo is better than adjuvant RT: retrospective data Lucky MA, Rogers B, Parr NJ. Referrals into a dedicated British penile cancer centre and sources of possible delay. Sex Transm Infect 2009
  • 16. Role of chemotherapy Adjuvant: Italian group: 1979-1990 25 pts treated with weekly VMB (VCR, bleomycin, mtx): for 12 couses Compared to retrospective cohort of 35pts Median f/u 42 months Long term DFS: 84% vs 39%
  • 17. N: 19 pts Median f/u: 15.3 months Median DFS was 16.2 months Median OS was not reached
  • 18. No data available on adjuvant in pN1 disease
  • 19. NACT for fixed or relapsed nodes Small retrospective studies of 5-20 patients have reported bleomycin-vincristine- methotrexate (BVM) and bleomycin- methotrexate-cisplatin (BMP) Hakenberg OW, Nippgen JB, Froehner M, et al. Cisplatin, methotrexate and bleomycin for treating advanced penile carcinoma. BJU Int 2006 Leijte JA, Kerst JM, Bais E, et al. Neoadjuvant chemotherapy in advanced penile carcinoma. Eur Urol 2007
  • 20. N : 28 irinotecan (60 mg/m2) on days 1, 8 and 15 and cisplatin (80mg/m2) administered every 28 days T3/4, N1-3, M1 were included Failed to demonstrate a response rate of more than 30%
  • 21. N: 30 N2/3 disease, non metastatic ORR: 50% Median f/u 34 months 30% remained alive and disease free TTP and OS was significantly associated with Response Absence of bilateral residual tumor Absence of PNE
  • 22. N : 29 Locally advanced or metastatic Doce: 75mg/m2 d1, CDDP: 60mg/m2 d1, 5FU: 750mg/m2 day1-5 Primary outcome: objective response OR: 38.5% Grade 3/4 toxicity: 65.5%
  • 23. Advanced metastatic and relapsed disease Palliative chemotherapy Initial studies showed response to cisplatin Recent studies have shown even better response on addition of taxanes Virtually no data on second lien therapy Upcoming data on EGFR blockade Cetuximab, panitumumab
  • 24. Studies in the metastatic settings
  • 25. N: 25 Single agent paclitaxel 175mg/m2 q 3 wks PR: 20% Median PFS: 11wks Median survival 32 weeks
  • 26. Retrospective anaysis N: 26 Taxane with platinum Median PSF: 96days (approx: 13wks) Median OS: 246 days (approx: 35wks)
  • 27. Case reports 2 cases Prolonged survival
  • 28. Place of targeted therapies Retrospective 13 pts Median PFS: 3.2mo Median OS: 9.8mo