Penile cancer is treatable, but the arsenal is slim

In men in the United States, incidence-based mortality (IBM) is increasing for penile cancer, even though incidence has remained constant from 2000 to 2018.

Among men in the United States, incidence-based mortality (IBM) is increasing for penile cancer, even though incidence has remained constant from 2000 to 2018. Existing treatments are of limited effectiveness and there are had a lack of research that could identify better options.

Penile squamous cell carcinoma (PSCC), the most common form of the disease, is a rare cancer in high-income countries, with a prevalence of less than 1%. In contrast, the disease accounts for up to 10% of cancers in men in parts of Africa, Asia and South America.1 The American Society of Clinical Oncology estimates that 2,070 people will be diagnosed in the United States this year. In 2020, it was estimated that 36,068 people worldwide were affected by this disease.2

The disease can be fatal, but treatment is often successful, especially when diagnosed early. The 5-year overall survival (OS) rate in the United States for patients with this disease is 65%. For men with local disease, the 5-year OS rate is 80%, decreasing to 9% for those with distant metastases.2

However, the 5-year relative survival rate decreased slightly but steadily, from 67.7% from 2000 to 2004 to 65.67% from 2010 to 2014.3 Philippe E. Spiess, MD, MS, associate chief of surgical services and senior member of the department of genitourinary oncology at the Moffitt Cancer Center, as well as professor of oncology and urology in the department of urology at the University of South Florida Morsani College of Medicine said medical science just hasn’t done enough for these patients.

“The simple reason I think we’re seeing this, unfortunately, is that we haven’t developed, or identified, very effective systemic therapies for penile cancer patients. Often we can cure the cancer. early penis, fortunately,” said Spiess Live®. “However, when patients have advanced disease, I think we still struggle to identify good chemotherapies or immunotherapies or combination treatments that will be very effective for patients.”

The current standard of systemic care is 4 cycles of the TIP chemotherapy regimen, which includes neoadjuvant paclitaxel 175 mg/m2 on day 1 plus 1200 mg/m2 ifosfamide and 25 mg/m2 of cisplatin on days 1 and 3 for patients with N2 and N3 disease. In a landmark phase 2 study published in 2010, 23 out of 30 men completed all 4 treatment cycles. The overall response rate in these patients with this approach was 50% (95% CI, 31% to 69%), which included 3 complete responses and 12 partial responses (PR).4

More recently, investigators in China evaluated 19 men with advanced CCSP who received TIP treatment from June 2009 to June 2019. Five men have already had partial penile amputations. The other 14 had local carcinoma and fixed inguinal lymph node metastases.5

Twelve patients (63.1%) obtained PR and were operated. Five patients underwent bilateral inguinal lymphadenectomy (ILND) and pelvic lymph node dissection (PLND), and 6 had partial penile amputation plus ILND and PLND. One patient had penectomy plus ILND and PLND.

“Early-stage penile cancer is curable with surgery alone,” said Hao G. Nguyen, MD, PhD, Goldberg-Benioff Endowed Professor of Cancer Biology and Professor in the Department of Urology at the University of San Francisco. Live®. “We have been relying on the same chemotherapy for about ten years. We have not made progress in terms of treating metastatic disease. [That is why] you see a static survival rate, even a slight decline, for penile cancer.

He added that awareness of the disease is low and there is no established strategy for prevention or early detection. Additionally, there is no biomarker or pathway to identify PSCC and although the disease is associated with human papillomavirus (HPV), there is no evidence showing that the HPV vaccine prevents the disease. penile cancer.

Depending on the size and extent of the lesion, partial or total penectomy is considered the standard oncological treatment. However, amputation is disfiguring and has a significant negative effect on quality of life (QoL). European Urological Association guidelines recommend penis-sparing surgery whenever possible and some evidence suggests that less invasive surgery is just as effective.

In a systemic review of 88 studies involving 9,578 men, European researchers found a 5-year disease-free rate of 82.0% with penile-sparing surgery versus 83.9% with amputation. Studies reporting low recurrence-free rates involved patients who had undergone penile-sparing surgery for advanced disease. In contrast, those reporting higher recurrence-free rates were from cohorts who underwent amputation for less advanced disease.6

Whichever method is chosen, surgery has a negative impact on quality of life. Additionally, patients reported more concerns about appearance and interference with life due to disfigurement following amputative surgery. The investigators cautioned that the quality of the evidence was low, but the results support the use of penile surgery, if possible.

Gender and sexuality raise unique concerns

It has been documented that patients are very concerned about organ function after treatment. The surgery “is commonly associated with mutilation,” according to 1 report, and affects sexual and urinary function and health-related quality of life.

“Our goal is to have organ-sparing surgery without compromising oncological control in our surgical approach,” Nguyen explained. “I would say depending on the location, if the lesion is at the end of the gland, then most of the time, even in T2 disease, you have to [be able to] spare much of the organ.

Spiess said the surgery has important ramifications for cisgender, non-binary and transgender patients. Preservation of sexual function is essential for physical and emotional health.

“One thing with this type of cancer, which is under-reported, is the implications it has for how patients identify after having undergone sometimes, unfortunately, quite mutilating surgery of the penis and that area, and how it affects their sexual identity, and their relationships with their partners,” Spiess said. “What I do in my practice, and several centers have started doing this as well, is [leverage] psychosocial counselors and educators essential for working with patients. We screen them for depression, for suicidal thoughts. [Traditionally,] this is something that has not been done very frequently. We must be very aware [of this,] and support our patients [to help them to understand] how it will affect them. And it will last for many, many more years. »

Spiess and Nguyen agreed that shame can prevent patients from seeking treatment. Results from a small study at Örebro University Hospital in Sweden showed that 65% of patients delayed treatment for more than 6 months.seven Data show that a delay of just 3 months was associated with increased risks of adverse clinical features, low penile sparing rate, and poor restoration of sexual function.8

Among patients who delayed treatment, 23.2% said they were embarrassed to describe the problem to practitioners. Another 19.5% of patients said they did not think their symptoms were severe.seven

“To counter this, we need to create a way to screen for penile cancer in the healthcare system. We screen for prostate cancer; we screen for colorectal cancer,” Nguyen said. “Why not ask every man to have a penis exam every year? Then it takes away those feelings or emotions associated with the review, and it just makes it more objective.

References

  1. Thomas A, Necchi A, Muneer A, et al. Penile cancer. Nat Rev Dis Primers. 2021;7(1):11. doi:10.1038/s41572-021-00246-5
  2. Penile cancer: statistics. Cancer.net website. February 2022. Accessed June 27, 2022. https://bit.ly/3OslSRD
  3. Deng X, Liu Y, Zhan X, et al. Trends in penile cancer incidence, mortality, and survival in the United States: a population-based study. front oncol. Published online June 17, 2022. doi: 10.3389/fonc.2022.891623
  4. Pagliaro LC, Williams DL, Daliani D, et al. Neoadjuvant chemotherapy with paclitaxel, ifosfamide and cisplatin for metastatic penile cancer: a phase II study. J Clin Oncol. 2010;28(24):3851-3857. doi:10.1200/JCO.2010.29.5477
  5. Xu J, Li G, Zhu SM, et al. Neoadjuvant chemotherapy combined with docetaxel, cisplatin and ifosfamide (ITP) for the treatment of patients with penile squamous cell carcinoma with end-stage lymph node metastases. CMB Cancer. 2019;19(1):625. doi:10.1186/s12885-019-5847-2
  6. Sakalis VI, Campi R, Barreto L, et al. What is the most effective primary tumor management in men with invasive penile cancer: a systematic review of available treatment options and their outcomes. Euro Urol Open Sci. 2022;40:58-94. doi:10.1016/j.euros.2022.04.002
  7. Skeppner E, Andersson SO, Johansson JE, et al. Initial symptoms and delay in patients with penile carcinoma. Scand J Urol Nephrol. 2012;46(5):319-325. doi:10.3109/00365599.2012.677473
  8. Gao W, Song Lb, Yang J, et al. Risk factors and negative consequences of patient delay for penile carcinoma. World J Surg Oncol. 2016;14:124. doi:10.1186/s12957-016-0863-z

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