Morten Frisch, epidemiologist,^a Soren Friis, epidemiologist,^b Susanne Kruger Kjaer

epidemiologist,^b Mads Melbye, research professor ^a

^a Danish Epidemiology Science Center, Statens Seruminstitut, DK-2300 Copenhagen S, Denmark, ^b Danish Cancer Society, Research Center, Division for Cancer Epidemiology, Copenhagen, Denmark

Correspondence to: Dr Frisch.

Boys circumcised neonatally are effectively protected against penis cancer.¹ Using data from the Danish Cancer Registry we investigated the long term trends in the incidence of penis cancer in a virtually uncircumcised population.

Patients, methods, and results

Penis cancers diagnosed in Denmark during 1943-90 and notified to the cancer registry were evaluated manually. We excluded scrotal and epididymal cancers and 39 non-epidermoid penis cancers (20 basal cell carcinomas, nine melanomas, and 10 others). World standardised incidence rates were calculated and linear regression applied to evaluate the temporal changes in incidence (five year data) and age distribution. We evaluated the impact of marital status in a case control design using patients with colon and stomach cancers diagnosed in the same period as controls. The odds ratios of never having married were calculated using logistic regression.

The material comprised 1523 epidermoid penis cancers (including 207 without specified histology). Patients were 22 to 95 years old at diagnosis. Incidence rates fell 0.5% a year from 1.15 (95% confidence interval 0.94 to 1.36) in 1943-7 to 0.82 (0.65 to 0.99) per 100000 person years in 1988-90 (P=0.002) (figure).

Of 1516 patients with information available about marital status at the time of diagnosis, 10.6% had never married. The corresponding percentages among control patients with colon and stomach cancer were 7.3% and 8.6%, respectively. The mean age at diagnosis increased among men who had ever married from 64 years in 1943-62 to 67 years in 1978-90 (P<0.0001). Patients with penis cancer who had never married living in the Copenhagen area were generally younger (mean age 60 years). After adjustment for age (10 year intervals), calendar period (five year periods), and place of residence (Copenhagen and suburbs v rest of Denmark), patients with penis cancer were significantly more likely to have remained unmarried than patients with colon cancer (odds ratio=1.4; 95% confidence interval: 1.2 to 1.6). This applied in different strata of age and calendar period, and a particularly high risk was found for unmarried men in the Copenhagen area (odds ratio=1.9; 1.4 to 2.6). Compared with patients with stomach cancer, the association with unmarried marital status was not present (odds ratio=1.1; 0.97 to 1.4), except among those living in the Copenhagen area (odds ratio=1.7; 1.2 to 2.3).

Comment

Improvements in diagnostic methods can be ignored when considering factors influencing the incidence of penis cancer. Also, the proportion of undiagnosed or misclassified cases is likely to be negligible.

With phimosis and penis cancer as two central issues, neonatal circumcision has been the subject of considerable debate for more than a century.^{2 3} The virtual absence of penis cancer in populations prescribing neonatal circumcision has been a crucial argument in this discussion.¹ However, only 511 out of approximately 478000 Danish boys aged 0-14 years were circumcised in 1986 (National Board of Health, personal communication), corresponding to a cumulative national circumcision rate of around 1.6% by the age of 15 years. Thus, the declining incidence of penis cancer in Denmark cannot reasonably be attributed to an increased practice of neonatal circumcision.

The observed association with marital status might be explained by socioeconomic and hygiene factors. The finding that patients with penis cancer and patients with stomach cancer who predominate in lower socioeconomic strata had rather similar marital status patterns supports this.⁴ Also, even though it is not established how and to what extent men who had never or ever married differ in sexual behaviour, it seems plausible that within the broad category of men who had never married, the proportion of men with lifestyles characterised by unstable partner relations and poor genital hygiene may be larger than among men who had ever married. This might particularly be so in the Copenhagen area, the only metropolitan area of Denmark. During the period under study, the proportion of Danish dwellings having a bath increased gradually from 35% in 1940 to 90% in 1990.⁵ It seems plausible that better penile hygiene resulting from this improvement in sanitary installations might have contributed to the observed trend.

Funding: Danish Cancer Society.

Conflict of interest: None.

1.                    Wolbarst AL. Circumcision and penile cancer. Lancet 1932;i:150-3.

2.                    Remondino P. History of circumcision (1st ed). Philadelphia: F A Davis Co, 1891.

3.                    Gordon A, Collin J. Save the normal foreskin. BMJ 1993;306:1-2.

4.                    Nomura A. Stomach. In: Schottenfeld D, Fraumen J Jr, eds. Cancer epidemiology and prevention. Philadelphia: Saunders, 1982:624-37.

5.                    Danmarks Statistik. Statistisk arbog 1943:32; 1991:73.

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Although it is not known exactly what causes penis cancer there are some risk factors that appear to make men more susceptible to the disease. Risk factors do not mean you will get penis cancer but they do, by definition, increase the chance. Cancer of the penis is very rare. Each year there are an estimated 1,295 cases in the USA, 143 cases in Canada and 265 cases in the UK.

Risk Factors for penile Cancer

Age Risk Factor for Penis Cancer

Over half of all penis cancers are diagnosed in men over the age of 68. It is very rare in men under the age of 40 years.

Human Papillomavirus Infection (HPV) Risk Factor for Penis Cancer

There are many types of Human Papillomavirus infection. HPV appears to be mostly transmitted during sexual contact though there is some debate about HPV being transmitted through infected underwear and wet towels. The type of HPV that causes genital warts is different to the type that can cause penile cancer.

Non Circumcised Men and Penis Cancer

Debate continues over whether being circumcised gives you protection from penis cancer. There is a lot of evidence to suggest other risk factors are more important e.g. HPV and smoking.

Smoking and Penis Cancer

Carcinogenic chemicals are taken into the body when you smoke. These chemicals (including benzyrene) can cause DNA damage and increases the risk of penile cancer.

Weakened Immune Systems and Penis Cancer

Various diseases including HIV and AIDS, or people who have to take medication to suppress their immune system are more susceptible to penis cancer.

Psoriasis as a Risk Factor for Penis Cancer

When psoriasis, a chronic skin condition, is treated with the drug psoralen in combination with phototherapy (light therapy) it can cause penis cancer.

Poor Penis Hygiene & Penis Cancer

Exactly how much someone’s poor penis hygiene contributes to penis cancer is not known. Doctors believe a build up of smegma can contribute and be a risk factor for penis cancer. However the research is not overwhelming. Good hygiene will help to prevent inflammation and other infections.

American Cancer Society

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Evidence for Multiple Independent Pathways of Penile Carcinogenesis

—      Mark A. Rubin^*, Bernard Kleter, Ming Zhou^*, Gustavo Ayala, Antonio L. Cubilla, Wim G. V. Quint^¶ and Edyta C. Pirog^||

^—        From the Department of Pathology,^*

^—        University of Michigan, Ann Arbor, Michigan; the Delft Diagnostic Laboratory,

^—        Delft, The Netherlands; the Department of Pathology,

^—        Baylor College of Medicine, Houston, Texas; the Department of Pathology,

^—        Universidad Nacional de Asuncion, Asuncion, Paraguay; the Academic Medical Center,^¶

^—        Amsterdam, The Netherlands; and the Department of Pathology,^||

Cornell University, New York, New York

To clarify the role of human papillomavirus (HPV) in penile cancer we evaluated the prevalence of HPV DNA in different histological subtypes of penile carcinoma, dysplasia, and condyloma using a novel, sensitive SPF10 HPV polymerase chain reaction assay and a novel genotyping line probe assay, allowing simultaneous identification of 25 different HPV types. Formalin-fixed, paraffin-embedded tissue samples were collected from the United States and Paraguay. HPV DNA was detected in 42% cases of penile carcinoma, 90% cases of dysplasia, and 100% cases of condyloma. There were significant differences in HPV prevalence in different histological cancer subtypes. Although keratinizing squamous cell carcinoma and verrucous carcinoma were positive for HPV DNA in only 34.9 and 33.3% of cases, respectively, HPV DNA was detected in 80% of basaloid and 100% of warty tumor subtypes. There was no significant difference in HPV prevalence between cases from Paraguay and the United States. In conclusion, the overall prevalence of HPV DNA in penile carcinoma (42%) is lower than that in cervical carcinoma (100%) and similar to vulvar carcinoma (50%). In addition, specific histological subtypes of penile cancer—basaloid and warty—are consistently associated with HPV, however, only a subset of keratinizing and verrucous penile carcinomas is positive for HPV DNA, and thus these two tumor groups seem to develop along different pathogenetic pathways.

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Xavier Castellsagué, M.D., F. Xavier Bosch, M.D., Nubia Muñoz, M.D., Chris J.L.M. Meijer, Ph.D., Keerti V. Shah, Dr.P.H., Silvia de Sanjosé, M.D., José Eluf-Neto, M.D., Corazon A. Ngelangel, M.D., Saibua Chichareon, M.D., Jennifer S. Smith, Ph.D., Rolando Herrero, M.D., Victor Moreno, M.D., Silvia Franceschi, M.D., for the International Agency for Research on Cancer Multicenter Cervical Cancer Study Group

Methods

We pooled data on 1913 couples enrolled in one of seven case–control studies of cervical carcinoma in situ and cervical cancer in five countries. Circumcision status was self-reported, and the accuracy of the data was confirmed by physical examination at three study sites. The presence or absence of penile HPV DNA was assessed by a polymerase-chain-reaction assay in 1520 men and yielded a valid result in the case of 1139 men (74.9 percent).

Results
Penile HPV was detected in 166 of the 847 uncircumcised men (19.6 percent) and in 16 of the 292 circumcised men (5.5 percent). After adjustment for age at first intercourse, lifetime number of sexual partners, and other potential confounders, circumcised men were less likely than uncircumcised men to have HPV infection (odds ratio, 0.37; 95 percent confidence interval, 0.16 to 0.85). Monogamous women whose male partners had six or more sexual partners and were circumcised had a lower risk of cervical cancer than women whose partners were uncircumcised (adjusted odds ratio, 0.42; 95 percent confidence interval, 0.23 to 0.79). Results were similar in the subgroup of men in whom circumcision was confirmed by medical examination.

Conclusions
Male circumcision is associated with a reduced risk of penile HPV infection and, in the case of men with a history of multiple sexual partners, a reduced risk of cervical cancer in their current female partners.

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THE Ministry of Health is planning to roll out male circumcision free of charge countrywide as a preventive strategy against HIV/AIDS. This comes in the wake of research that suggests circumcised men have a lower risk of contacting sexually transmitted diseases.

More than reducing the risk of contracting HIV/AIDS, professionals say, circumcision also helps in averting other medical complications such as penile cancer, urinary tract infections and the swelling of the foreskin.

Circumcision, however, does not provide complete protection against HIV infection. Health experts stress that circumcised men, like their uncircumcised counterparts, can still contract the virus that causes AIDS and infect their sexual partners.

There is fear that circumcised individuals risk acquiring and transmitting HIV should they not follow the surgeon’s prescriptions and engage in sexual intercourse during the recommended healing period. A person must avoid sex for about six weeks after circumcision to allow for healing. Men are also warned against leaning on circumcision as a shield against the deadly disease.

The mistaken notion that circumcision is a safe shield against the deadly disease, it is feared, has driven circumcised men into having unprotected sex with many partners, thereby putting their lives in greater danger.

I reiterate that circumcision only helps in reducing the risk of contracting the disease. As a comprehensive prevention method, it is advisable that one goes for HIV testing before committing to circumcision because this helps in knowing one’s status.

Health officials say adult male circumcision is safe when performed correctly by trained professionals. However, some people, especially in rural areas, may disguise themselves as surgeons and end up putting people’s lives at risk by cutting beyond the foreskin which results into prolonged bleeding and pain.

Circumcision comes in as an additional strategy to the Abstinence, Be faithful and Condom use (ABC). However, the health ministry should sensitise the public about it and what it entails through the media, local leaders and public debates for successful implementation.

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From the Department of Urology, Montefiore Hospital and Medical Center, and the Albert Einstein College of Medicine

[CIRP Note: This historic article conclusively disproves the false claims made by circumcision promoter Abraham Wolbarst in 1932 that circumcision prevents penile cancer. This article probably accurately reflects the state of medical knowledge at the time. The most important risk factors for penile cancer, which are the presence of human papilloma virus and use of tobacco, had not yet been discovered at the time this article was written. See Carcinoma in Situ of the Penis in a 76-Year-Old Circumcised Man for a more recent report on cancer in circumcised males.]

In Wolbarst’s¹ extensive review of 1,103 case of penile carcinoma he was unable to find even a single patient who had been circumcised in infancy. Since then there have been only eight documented cases of penile carcinoma in an individual circumcised in infancy. The following is the ninth reported case and the first since 1968.

Case report

A 78-year-old Jewish male appeared in the emergency room of Montefiore Hospital with fungating and purulent penile lesion in the region of the frenulum. The patient claimed that the lesion had been present for nearly three years and had failed to respond to various topical medications prescribed by numerous physicians. He maintained that he had been ritually circumcised at eight days of age, and this was corroborated by family members.

Significant history included an open prostatectomy nine years earlier. The old chart was reviewed and described a normal circumcised penis without abnormalities.

A biopsy of the penile lesion revealed squamous cell carcinoma. No metastases were found, and the patient underwent a partial penectomy. Histologic examination showed a well-differentiated squamous cell carcinoma with extensive zones of invasion into the spongiosum; the margins of resection were free of tumor.

The patient recovered uneventually and was well one year postoperatively, after which he was lost to followup.

Comment

Circumcision is the oldest known surgical procedure, dating back more than 6,000 years according to Herodotus. Certain tribes with mother goddess figures, such as Ishtar and Cybele, in the ancient matriarchal religions, required the sacrificial offering of external male genitalia. As castration would have inevitably led to extinction of the tribe, it gave way to circumcision. The Hittites and the Amorites were also practicing this procedure when Abraham introduced mandatory ritual circumcision, in 1813 B.C. for all Hebrew males at the age of eight days. The ancient Hindus regarded the genitalia as the center of life and sacrificed the prepuce as a valuable offering to the gods. However, they no longer practice routine circumcision. Moslems continue to circumcise all males between 4 and 10 years of age.

There have been a number of articles published on the high incidence of penile carcinoma in Hindus who do not practice routine circumcision as compared with the Moslems who do.² During the Roman period, certain religious activities could only be performed by circumcised priests, but the general population was not circumcised.

Circumcision arose independently in the ancient Orient, Africa, and Polynesia as a pubertal or premarital rite, as well as a test of a man’s ability to withstand pain. The females of certain African tribes are said to have demanded circumcision of their husbands, believeing that it decreased the sensitivity of the glans and, as a result, prolonged coitus. The practice gradually spread westward, and by the nineteenth century was well established on the European continent. In 1891 Remondino³ devoted an entire book to the various aspects of circumcision and described the prepuce as “tight constricted, glans deforming, onanism producing, and cancer generating.”³

Cancer of the penis has also been recognized for thousands of years. Celsus recommended amputation for penile carcinoma with cauterization of the raw stump to control bleeding. In the seventeenth century, Scultetus used fire to destroy the tumor. The morbidity of the surgery in those days probably approached that for the disease itself.

In this country, the incidence of penile carcinoma is about 1 percent of male cancers.⁴ However, in countries where routine circumcision is not practiced, its incidence has been reported as high as 18 percent.⁵ While numerous reviews since Wolbarst¹ have confirmed his observation and corroborated the protective effect of circumcision, it has become apparent that this protection decreases if the circumcision is performed in later life. Lenowitz and Graham studied this group and found penile carcinoma occurring on an average of 22 years after the circumcision.⁶ A chronic irritative state, resulting from years of phimosis and balanoposthitis prior to the circumcision, has been postulated to explain this long latent period.

The incidence of phimosis in reviews of penile carcinoma ranges from 40 to 70 percent.^7,8 Smegma, a sterol, produced by Tyson’s glands in the epithelium of the retroglandular sulcus, has been implicated as the causative agent. It may be converted to a carcinogen by the action of the Mycobacterium smegmatis. Plaut and Kohn-Speyer⁹ weer able to produce malignant skin lesions in mice, using smegma, but other investigators have been unsuccessful in confirming its carcinogenicity.

In 1936, the first case of penile carcinoma in a circumcised Jewish male was reported by Dean.¹⁰ In this patient the neoplasm developed in an old scar resulting rom cautery for a venereal wart. Four more cases in circumcised Jewish males have been reported.^11-14 There have also been three cases of penile carcinoma in gentiles who were reportedly circumcised in infancy.^15,16 In four of these eight cases there was a history of trauma to the penis preceding the development of cancer.

The diagnosis in our patient was made late, as in the other cases reported, perhaps because the disease was presumed not to occur in those circumcised in infancy. This is clearly not so. Although rare, the diagnosis must be considered when evaluating a penile lesion even in a circumcised individual.

Circumcision originated with the ancient tribes, and its basis can hardly be considered scientific. Nonetheless, performing it in infancy continues to be the most effective prophylactic measure against penile carcinoma.

Summary

The ninth case of squamous cell carcinoma of the penis in an individual circumcised in infancy is reported. The history of circumcision and its relationship to penile carcinoma is reviewed.

References

1.                    Wolbarst, A.L.: Circumcision and penile carcinoma, Lancet 1:150 (1932)

2.                    Harlin, H. C.: Cancer of the penis, J Urol. 67: 326 (1952).

3.                    Remondino P: History of circumcision. 1st ed., Philadelphia, Pa., F.A. Davis Co., 1891.

4.                    Persky, L., and deKernion, J.: Carcinoma of the penis, Cancer 26: 130 (1976)

5.                    Dodge, O. G.: Carcinoma of the penis in East Africans, Brit. J. Urol. 37: 223 (1965)

6.                    Lenowitz, H., and Graham, A.: Cancer of the penis. J. Urol. 56: 458 (1946)

7.                    Thomas, J. A., and Small, C.S.: Carcinoma of the penis in Southern India, ibid 100: 520 (1968)

8.                    Hardner, G. J., et al.: Carcinoma of the penis: analysis of therapy in 100 consecutive cases. ibid. 108: 428 (1972)

9.                    Plaut, A., and Kohn-Speyer, A.C.: Carcinogenic action of smegma, Science 105: 391 (1947)

10.                 Dean, A. L., Jr.: Epithelioma of the penis in a Jew who was circumcised in infancy, Tr. Am. A. GU Surg. 29: 493 (1936)

11.                 Marshall, V. F.: Typical carcinoma of the penis in a male circumcised in infancy, Cancer 6: 1044 (1953)

12.                 Reitman, P. H.: An unusual case of penile carcinoma. J. Urol. 69: 547 (1953)

13.                 Paquin, A. J., Jr., and Pearce, J. M.: Carcinoma of the penis in a man circumcised in infancy, ibid. 74: 626 (1955)

14.                 Melmed, E. P., and Pyne, J. R.: Carcinoma of the penis in a Jew circumcised in infancy, Brit. J. Surg. 54: 729 ( 1967)

15.                 Amelar, R.: Carcinoma of the penis due to trauma occurring in a male patient circumcised at birth, J. Urol. 75: 728 (1956)

16.                 Ledlie, R. C., and Smithers, D.W.: Carcinoma of the penis in a man circumcised in infancy, ibid. 76: 756 (1956).

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In Stage I, malignant cells are found only on the surface of the head (glans) of the penis.

In Stage II, the penile cancer has spread to the surface of the glans, tissues beneath the surface, and the shaft of the penis.

In Stage III, malignant cells have spread to lymph nodes in the groin, where they cause swelling.

In Stage IV, the disease has spread throughout the penis and lymph nodes in the groin, or has traveled to other parts of the body.

Recurrent penile cancer is disease that recurs in the penis or develops in another part of the body after treatment has eradicated the original cancer cells.

Treatment

Surgery and radiation therapy

Amputation of all or part of the penis (total or partial penectomy) is the most common and most effective treatment. If the disease is diagnosed early enough, surgeons are often able to preserve enough of the organ for urination and sexual activity.

Wide local excision is a form of surgery that removes only cancer cells and a small amount of normal tissue adjacent to them. Microsurgery removes cancerous tissue and the smallest possible amount of normal tissue. During microsurgery, the doctor uses a special instrument that provides a comprehensive view of the area where cancer cells are located and makes it possible to determine that all malignant cells have been removed. Laser surgery uses an intense precisely focused beam of light to dissolve or burn away cancer cells.

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Marc T. Goodman, Brenda Y. Hernandez and Yurii B. Shvetsov

Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii

Objective: Penile cancer is an uncommon malignancy, so few descriptive or analytic studies have been reported in the literature. The objective of this analysis was to describe the distribution of penile cancer in the United States by demographic, pathologic, and clinical features.

Methods: Penile cancer among 6,539 men was identified through 29 population-based registries in the United States during the period 1995-2003. These registries were estimated to represent 68% of the U.S. population. Age-adjusted incidence rates were calculated per million population using counts derived from the 2000 U.S. census. A subset of nine registries was used to examine time trends in penile cancer between 1973 and 2003.

Results: Squamous cell carcinomas were the most common histologic type of penile cancer, representing 93% of all malignancies. Hispanic men had the highest age-adjusted incidence rates per million for penile cancer (6.58 per million), followed by Blacks (4.02 per million), Whites (3.90 per million), American Indians (2.81 per million), and Asian-Pacific Islanders (2.40 per million). The highest rates of penile cancer were found among Hispanic men (46.9 per million) and Black men (36.2 per million) of ages 85 years. Penile malignancy was rare among males under age 20 years. Time trend analysis supported a significant decrease in the incidence of penile cancer for Blacks (annual percent change, –1.9%) and Whites (annual percent change, –1.2%). The majority (61%) of penile cancers were diagnosed at a localized stage among all racial and ethnic groups, although Hispanic and Black men tended to be diagnosed at more advanced stages than Whites. No racial or ethnic differences in tumor grade were identified. The incidence of penile cancer was highest in the South (4.42 per million) and lowest in the West (3.28 per million) of the United States. The highest age-adjusted incidence rate was found among Black men in the South (4.77 per million) and the lowest rate among Asian-Pacific Islanders in the West (1.84 per million).

Conclusions: This analysis showed significant racial/ethnic and regional variation in the incidence of penile cancer. The high rate of penile cancer among Hispanic and Southern Black men suggests differences in risk factors for this malignancy, such as circumcision, hygiene, or human papillomavirus exposure. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1833–9)

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Cancer that is easily misdiagnosed. Learning about the disease is, therefore, especially important for men.

Answering questions about penile cancer is Curtis A. Pettaway M.D., associate professor in M. D. Anderson’s Department of Urology.

What is penile cancer?

Penile cancer is a malignant growth starting in the epithelium (surface) of the glans penis (head of the penis) or the shaft. It is very rare, affecting less than one in 100,000 males.

Squamous cell carcinoma represents the most common type of penile cancer and accounts for about 95% of cases.

Other types of penile malignancy include:

—      Sarcoma

—      Melanoma

—      Lymphoma

—      Leukemia

Occasionally the penis also will be a site where cancer spreads from primary sites such as the bladder, prostate and rectum.

How many cases of penile cancer are treated at M. D. Anderson each year?

Approximately 30 patients with penile cancer are seen yearly at M. D. Anderson. Although this seems like a relatively small number of cases, the average urologist will see about one case every five years. For these reasons it is difficult to perform large clinical trials to determine the best ways to treat the disease or evaluate new therapies.

The incidence rates in certain countries such as Cuba, Brazil, Columbia, India and Paraguay are two to four times that of the United States and relate directly to the practice of neonatal circumcision, personal hygiene, and the prevalence of human papilloma virus (HPV) infection. Many of the articles related to penile cancer come from the above countries where the incidence is higher.

What are the causes, risk factors and preventive measures?

Most penile cancers are diagnosed in men between the ages of 50 to 70 years of age. However, about 30% of cases occur in men who are 50 years of age or less.

Risk factors include:

—      Lack of neonatal circumcision

—      Phimosis (difficulty retracting foreskin)

—      Human papilloma virus infection

—      Tobacco products

Among groups that practice neonatal circumcision, the rates of penile cancer are rare. The foreskin is believed to harbor bacteria, body oils and debris (collectively called smegma) that if not properly cleaned, can lead to repeated episodes of inflammation, which leads to scarring of the foreskin and phimosis. Foreskins removed due to phimosis often have atypical cells noted by the pathologist.

Other modifiable risk factors also can contribute to the development of penile cancer in men with a foreskin.

Human papilloma virus infection is a known cause of cervical cancer. Virus types 16 and 18 are the predominant types implicated in penile cancer. As HPV is a sexually transmitted phenomenon, a significant portion of both penile and cervical cancers could be prevented. Of importance: not all types of HPV infection can cause cancer. Specifically, types 6 and 11 - while associated with the presence of viral warts - have not been associated with cancer.

Tobacco products are known carcinogens implicated in lung, bladder, head and neck and renal cancers and also are implicated in penile cancer. The risk of penile cancer is increased in men who smoke or chew tobacco products, even when considering those who are circumcised.

How is penile cancer treated?

Natural history

Carcinoma of the penis usually begins with a small lesion, which gradually extends to involve the entire glans and then the penile shaft. The most common site of spread is to the inguinal lymph nodes. If untreated, the inguinal metastases enlarge, ulcerate through the skin (causing infection) or grow into the adjacent femoral vessels producing hemorrhage (and potentially death).

The goals of treatment are to control the primary tumor and to diagnose and treat inguinal metastases at the earliest possible time point.

Primary tumor

Treatment to control the primary tumor includes:

—      Partial or total penile amputation

—      Limited excisions

—      Radiation therapy

—      Laser ablation

Chemotherapy has been reported to treat the primary tumor with only limited success.

The most effective therapy to treat the primary tumor is partial or total amputation. Success rates vary from 92% to 100% in preventing local recurrence. However, sexual quality of life is naturally decreased in men treated with amputation.

Recent data suggests that in select patients with low-grade/low-stage tumors, penile preservation is feasible with low to moderate tumor recurrence rates (8% to 33%). This does not appear to compromise survival in patients who are followed closely. Overall, for men with a treated primary tumor who are at low risk of the cancer spreading, the five-year, disease-free survival rate is approximately 90%.

At M. D. Anderson penile preserving strategies are available for appropriate candidates.

How is penile cancer that has spread treated?

The extent of regional lymph node metastasis dictates survival in penile cancer. Good prognostic factors in patients undergoing surgery whose penile cancer has spread to the groin include:

—      A maximum of one to two nodes located on only one side of the groin area, versus both sides

—      No extranodal extension - invasion of cancer through the lymph node into the surrounding tissue

—      No spread to the pelvic lymph nodes

Current strategies are aimed at defining the presence of microscopic disease in the nodes so that surgery can be performed earlier with a higher curative potential. Unfortunately, even if the physical examination is negative for nodal enlargement, metastases are present in about 25% of patients. Because inguinal surgery can be associated with complications, it is prudent to try to define which patients are at highest risk.

Recently, we developed prognostic categories to define which patients without lymph node enlargement on physical examination might still have microscopic disease in the inguinal (groin) lymph nodes.

Patients in the low-risk group are observed. Those in the high-risk group undergo modified groin dissections or lymph node mapping to try and define where in the surgical field the cancer has spread. In this manner we can limit the morbidity of the procedure for our patients, while aggressively treating those who actually have metastasis.

Overall, for patients with limited inguinal disease the five-year, disease-free survival rate is between 60% and 80%. For those patients with poor prognostic factors, the five-year survival rate is 0% to 10%. In this latter group, we are pioneering the use of chemotherapy prior to surgical resection to potentially improve outcomes. Preliminary results are encouraging in those patients who respond to chemotherapy.

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Bernhard Scher, MD¹, Michael Seitz, MD², Martin Reiser, BS¹, Edwin Hungerhuber, MD², Klaus Hahn, MD¹, Reinhold Tiling, MD¹, Peter Herzog, MD³, Maximilian Reiser, MD³, Peter Schneede, MD² and Stefan Dresel, MD¹

1.        Department of Nuclear Medicine, University of Munich, Munich, Germany

2.        Department of Urology, University of Munich, Munich, Germany

3.        Department of Radiology, University of Munich, Munich, Germany

The value of PET or PET/CT with ¹⁸F-FDG for the staging of penile cancer has yet to be determined. The objective of this study was to investigate the pattern of ¹⁸F-FDG uptake in the primary malignancy and its metastases and to determine the diagnostic value of ¹⁸F-FDG PET/CT in the staging and restaging of penile cancer. Methods: Thirteen patients (mean ± SD age, 64 ± 14.0 y) with suspected penile cancer or suspected recurrent disease were examined with a Gemini PET/CT system (200 MBq of ¹⁸F-FDG). The reference standard was based on histopathologic findings obtained at biopsy or during surgery. Results: Both the primary tumor and regional lymph node metastases exhibited a pattern of ¹⁸F-FDG uptake typical for malignancy. Sensitivity in the detection of primary lesions was 75% (6/8), and specificity was 75% (3/4). On a per-patient basis, sensitivity in the detection of lymph node metastases was 80% (4/5), and specificity was 100% (8/8). On a nodal-group basis, PET/CT showed a sensitivity of 89% (8/9) in the detection of metastases in the superficial inguinal lymph node basins and a sensitivity of 100% (7/7) in the deep inguinal and obturator lymph node basins. The mean ± SD maximum standardized uptake value for the 8 primary lesions was 5.3 ± 3.7, and that for the 16 lymph node metastases was 4.6 ± 2.0. Conclusion: According to our results, the main indication for ¹⁸F-FDG PET in the primary staging or follow-up of penile cancer patients may be the prognostically crucial search for lymph node metastases. With the use of a PET/CT unit, the additional information provided by CT may be especially useful for planning surgery. Implementing ¹⁸F-FDG PET and PET/CT in future staging algorithms may lead to a more precise and stage-appropriate therapeutic strategy. Furthermore, invasive procedures with a high morbidity rate, such as general bilateral lymphadenectomy, may be avoided.

Key Words: PET/CT • ¹⁸F-FDG • penile cancer

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