Penile and Urethral Carcinoma

Penile and urethral carcinomas are rare. Most physicians will never be involved in the management of such a case. Because of their rarity, delay in diagnosis secondary to both patient and physician factors are a constant threat. Any lesion of the penis that cannot be definitively diagnosed must be considered cancer until otherwise proven. Steps must then be taken to establish a definitive diagnosis or the patient should be referred to an appropriate consultant. Urethral cancer in men frequently masquerades as a urethral stricture.

The annual meeting of the American Urological Association was held in San Antonio, Texas, May 21-26, 2005. At this meeting, a number of papers were presented on these topics.

One of the most striking presentations was on the coordinated chemoradiation therapy with genital preservation in the management of invasive carcinoma of the male urethra presented by a group from the Lahey Clinic.^[1] The report encompasses experience with 14 patients during a 13-year period, which concluded in September 2004. Thirteen patients had squamous cell carcinoma and 1 had adenocarcinoma. The cancer originated in the pendulous urethra in 5 patients and in the bulbomembranous urethra in the remaining 9. In 8 of 14 patients, the presenting problem was a urethral stricture. The remaining patients complained of a painful mass, penile ulceration, low urinary tract symptoms, or penile pain. The patients were found to have T2, T3, or T4 disease. In all cases, the diagnosis was established by urethral biopsy. Initial treatment for all patients was suprapubic cystostomy urinary diversion. External beam radiation was then administered to the primary site and to both inguinal areas. A continuous infusion of fluorouracil was administered, starting on the first day of radiation and continuing for 4 days. In addition, a single dose of mitomycin was given on day 1. Radiation consisted of 45 Gy in 25 fractions for 35-45 days. The chemotherapy treatment was repeated approximately 1 month later usually on the last 4 days of the radiation treatment.

The treatment protocol followed by the Lahey Clinic group was a modification of one proposed and used by Dr. Norman Nigro and his colleagues for carcinoma of the anus.^[2] The Nigro protocol has become the standard treatment for patients with carcinoma of the anus. Combined chemoradiation therapy is used for other sites as well. The Lahey Clinic group published their initial experience in the British Journal of Urology,^[3] but this paper described only 2 patients. However, the results were so superior to standard treatment that the group was encouraged to treat successive patients. Of the 14 patients treated using this protocol, 12 showed no evidence of local recurrence. One patient died of metastatic disease and 2 patients had local recurrence. Despite these excellent results with genital preservation, complications are common and include urethral stricture, which in some cases requires urethral reconstruction. A severe radiation dermatitis is universal but is managed with supportive care.

Dr. Nick Watkin’s group from London, England, reported on organ-sparing surgery in primary anterior urethral cancer.^[4] Their abstract centers on 10 consecutive cases referred to 1 surgeon. Presenting complaints consisted of obstructive urinary symptoms, a meatal red patch, a bloodstained urethral discharge, or a palpable hard mass within the glans penis. Patients were staged as having T1, T2, or T3 disease. Penile-preserving surgery was offered to all patients. The surgery varied widely from patient to patient. Adjuvant radiotherapy and chemotherapy were given in selective cases. With a mean follow-up of 18 months, there were no local recurrences. One patient died of metastatic disease and another of an unrelated cause. Malignant nodal disease was treated by radical dissection.

Whether organ-sparing management will replace traditional approaches to urethral cancer remains an open question. However, all patients must be informed of the advantages and disadvantages of both the organ-sparing and traditional approaches.

The same London group also presented 2 papers on penile carcinoma. Their abstract “Total Glans Resurfacing for Preinvasive Carcinoma of the Penis: A New Approach”^[5] provided evidence that ablative therapy may be associated with high local failure rate and can also result in unsightly scars. They treated 8 patients in whom conventional therapy failed or who had significant residual glans deformity with total glans resurfacing. The procedure they used was originally described by Depasquale and associates for benign disease of the penis in the British Journal of Urology International.^[6] The procedure involves removal of the epithelial and subepithelial tissues of the glans in quadrants. Frozen sections are then taken from the underlying corpus spongiosum to confirm complete excision. A split-thickness skin graft was then used to cover the glans penis. With a mean follow-up of 16 months, no evidence of disease recurrence or premalignant change has been observed. No perioperative or postoperative complications or loss of skin graft were reported. Excellent cosmetic results were claimed.

The London group’s third abstract, entitled “Penile Preserving Surgery for Invasive Penile Cancer: The First 100 Cases from a UK Center,” reports on their policy of offering organ-preserving surgery whenever possible as an alternative to the more traditional penile amputation or radical radiotherapy.^[7] Of the 100 patients they describe, 7 needed only nodal surgery. Of the remaining 93, 13 required conventional partial or radical penectomy. Thus, 80 patients were offered organ-preserving surgery. The precise surgery performed varied widely from patient to patient. With a mean follow-up of approximately 19 months, 2 patients have developed recurrence and 1 was found to have carcinoma in situ. These authors believe that nontraditional surgical techniques for invasive penile carcinoma have achieved excellent short-term results. We await a report on the long-term outcome.

Sentinel node biopsy has been of interest since Cabanas at the Memorial Sloan-Kettering Canner Center developed the concept in the 1970s.^[8] Briefly stated, the theory proposes that there is a sentinel node for penile cancer. If the sentinel node is found to be free of cancer, then the remaining lymph nodes should also be negative. This concept has the potential to spare patients needless radical lymph node dissection. The concept has never been universally accepted, and its use is controversial. An Italian group reported a comparison between dynamic sentinel node biopsy (DSNB) and radical inguinal lymphadenectomy in penile cancer.^[9] The group used a high-tech method of identifying the sentinel node. Preoperative lymphoscintigraphy was performed after intradermal injection of 99m technetium-nanocolloid around the primary tumor. The sentinel node was then identified intraoperatively with the aid of blue dye and a gamma ray detection probe. One month later, a radical inguinal lymphadenectomy was performed. This procedure was performed in 20 patients between 2001 and 2004. The results were compared to an earlier and larger group of 48 patients who received penectomy and a prophylactic radical inguinal lymphadenectomy later. In the earlier group of 48 patients, 40% had node-positive disease. In the present study, significant percentages of patients who received radical inguinal lymphadenectomy had minor short-term and major long-term complications. Impressively, all cases with negative DSNB results had no metastatic nodes found at lymphadenectomy. We await a long-term outcomes report. The interested reader is referred to a recent article on DSNB by Kroon and colleagues.^[10]

Minimally invasive techniques are being intensively studied for a variety of clinical surgical scenarios. Machado and coworkers^[11] presented a study that compared outcomes in patients with penile cancer treated with videoendoscopic radical inguinal lymphadenectomy (VEIL) and standard open lymphadenectomy. Only 3 patients were presented. The method of comparison was to perform the standard open procedure on one side and the VEIL procedure on the contralateral side. Mean follow-up was only 8 months. Mean operative time was approximately 1.5 hours for the VEIL procedure and approximately 2 hours for the standard technique. The mean number of lymph nodes was approximately the same for both techniques. No local recurrences were detected during the brief follow-up. There were no intraoperative or postoperative complications on the VEIL side. Weill-flap necrosis and lymphedema occurred in 2 of the 3 patients who received the open procedure. The authors believe that VEIL is an attractive alternative to standard technique. Again, longer follow-up is necessary.

A group from Vanderbilt University presented data on lymphadenectomy in squamous cell carcinoma of the penis.^[12] These authors report their experience with 41 patients during the past 10 years. After excluding 4 patients, 17 of the remaining 37 had palpable nodes and 20 had no palpable nodes. Of the patients with palpable nodes, 13 (76%) of the 17 had positive nodes at lymphadenectomy and 12% of those had a local recurrence. Of the 20 patients without palpable nodes, 14 did not develop nodal disease. However, 6 of the 20 developed nodal disease and underwent delayed lymphadenectomy. Recurrence at any part of the body occurred in 50% of the patients who underwent an immediate lymphadenectomy and in 83% of those who underwent delayed lymphadenectomy. Of those in the immediate lymphadenectomy group, 47% died, vs 66% in the delayed group. The groups, however, were not truly comparable. The authors believe that immediate lymphadenectomy is associated with lower local recurrence rate, longer disease-free survival, and lower mortality.

The search for the optimal management of penile and urethral cancer continues. Controversy revolves around organ-sparing vs non–organ-sparing techniques and minimally invasive vs standard techniques. Fortunately, these diseases are infrequent, but this very infrequency is impeding more rapid evolution of a consensus opinion.

References

1. Triaca V, Billmeyer B, Girshovich L, Shuster T, Oberfield R. Coordinated chemo-radiation therapy with genital preservation in the management of invasive carcinoma of the male urethra. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 442.
2. Nigro ND, Vaitkevicius VK, Considine B Jr. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum. 1974;17:354-356.
3. Oberfield RA, Zinman LN, Leibenhaut M, Girshovich L, Silverman ML. Management of invasive squamous cell carcinoma of the bulbomembranous male urethra with co-ordinated chemo-radiotherapy and genital preservation. Br J Urol. 1996;78:573-578.
4. Ahmed S, Hadaway P, Watkin N. Feasibility of organ sparing surgery for male primary anterior urethral cancer. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 441.
5. Singh R, Hadaway P, Corbishley C, Watkin N. Total glans resurfacing for preinvasive carcinoma of the penis: a new approach. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 440.
6. Depasquale I, Park A, Bracka A. The treatment of balanitis xerotica obliterans. BJU Int. 2000;86:459-465.
7. Hadaway P, Pietrzak P, Kommu S, Corbishley C, Watkin N. Penile preserving surgery for invasive penile cancer: the first 100 cases from a UK center. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 728.
8. Cabanas RM. An approach for the treatment of penile carcinoma. Cancer. 1977;39:456-466.
9. Perdonà S, Autorino R, De Sio M, et al. Dynamic sentinel node biopsy and radical inguinal lymphadenectomy in penile cancer: a comparative study. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 727.
10. Kroon BK, Horenblas S, Meinhardt W, et al. Dynamic sentinel node biopsy in penile carcinoma: evaluation of 10 years experience. Eur Urol. 2005;47:601-606.
11. Machado M, Tavares A, Molina W, et al. Comparative study between videoendoscopic radical inguinal lymphadenectomy (VEIL) and standard open lymphadenectomy for penile cancer: preliminary surgical and oncologic results. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 834.
12. Nelson B, Cookson M, Smith J, Shappell S, Chang S. Squamous cell carcinoma of the penis, a contemporary review of lymph node disease. Program and abstracts of the American Urological Association Annual Meeting; May 21-26, 2005; San Antonio, Texas. Abstract 726.

Richard J. Macchia, MD  

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