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Many men with penile cancer do not receive guideline-recommended care
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One-third of men with lymph node-positive penile cancer did not undergo lymph node dissection, despite the fact that the procedure is associated with improved OS, according to findings published in JAMA Oncology.
Also, fewer than half of patients received systemic therapy.
“These data highlight opportunities to improve adherence to guideline-recommended care,” Daniel Geynisman, MD, medical oncologist at Fox Chase Cancer Center, said in a press release accompanying the study.
The researchers used the National Cancer Data Base to retrieve data on 1,123 patients (82% white; 64.7% aged 50-75 years) with nonmetastatic lymph node-positive squamous cell carcinoma of the penis from Jan. 1, 2004, through Dec. 31, 2014.
Geynisman and colleagues evaluated the use of chemotherapy over time, and compared survival outcomes by whether patients received lymph node dissection, radiotherapy and chemotherapy.
In total, 66.8% of patients underwent lymph node dissection (n = 750).
The use of systemic therapy rose significantly from 2004 to 2014 (n = 26 of 68; 38.2% vs. n = 65 of 136; 47.8%; P < .001).
Only 52.8% of patients (n = 177 of 335) with N3 disease underwent chemotherapy. Slightly less than one-third (31.4%) of patients with N1 disease received chemotherapy, as did slightly more than one-third (39.6%) of patients with N2 disease.
Patients aged older than 76 years appeared less likely to receive chemotherapy after adjustment (OR = 0.28; 95% CI, 0.15-0.5). However, those with N2 disease (OR = 1.62; 95% CI, 1.16-2.27) or N3 disease (OR = 2.32; 95% CI, 1.67-3.22) appeared more likely to receive chemotherapy, as did those who underwent radiotherapy (OR = 4.38; 95% CI, 3.1-6.18).
Multivariable analysis showed that lymph node dissection was associated with better OS (HR = 0.64; 95% CI, 0.52-0.78), whereas radiotherapy (HR = 0.85; 95% CI, 0.7-1.04) and chemotherapy (HR = 1.01; 95% CI, 0.9-1.26) were not.
In an accompanying editorial, Barrett McCormick, MD, and Curtis Pettaway, MD, both of The University of Texas MD Anderson Cancer Center, noted that limitations acknowledged in the study, such as selection bias, retrospective data and lack of information on treatment regimens, meant that these results could not be used to support any specific treatment strategy. Rather, they wrote, the findings provided questions for the upcoming International Penile Advanced Cancer (InPACT) study.
“[The researchers] should be congratulated for providing needed insight into the management of lymph node-positive penile cancer among participating U.S. hospitals in the National Cancer Data Base,” McCormick and Pettaway wrote. “This study provides some useful baseline data and raises additional questions that may only be answered through multicenter clinical trials.” – by Andy Polhamus
Disclosures: Geynisman reports no relevant financial disclosures. One author reports research funding from Pfizer outside the of submitted work. Barrett and Pettaway report no relevant financial disclosures.
Perspective
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Treatment of penile cancer in the United States remains a challenge because of its rarity and resultant lack of data to guide management across the spectrum of the disease. Our current paradigms — including National Comprehensive Cancer Network guidelines — were developed with expert opinion and mostly referenced small retrospective studies. I applaud Joshi and colleagues for their effort and use of a large database to contribute to our understanding of penile cancer, especially as it relates to that of chemotherapy for clinical or pathological node-positive disease.
Although it is true that NCCN guidelines recommend lymph node dissection for clinically detected inguinal lymph node-positive disease, there are evolving considerations, including grade of primary tumor, use of percutaneous biopsy — especially in primary grade discordance (eg, grade 1 tumors) — and consideration of neoadjuvant chemotherapy. The punch line of this highlighted article is the suggestion that perioperative chemotherapy is used 48% of the time in lymph node-positive disease and that, in general, the use of lymph node dissection is associated with improved survival. Although the latter has been established, the appropriate use of perioperative chemotherapy is still an area of uncertainty. The lack of granularity of the National Cancer Data Base makes it hard to conjure up firm convictions as uncertain treatment paradigms, use of clinical stage (33% of node-positive cohort) and lack of primary staging (41% of cohort) challenge our interpretation. However, importantly, this article highlights that no center, regardless of self-identified status — academic, community, etc — sees an overwhelming number of patients with advanced penile cancer. Therefore, it is quite evident that this disease and other rare diseases will only be truly understood through multicenter collaboration and, ultimately, prospective clinical trials.
While we all await the International Penile Cancer Advanced Cancer Trial (InPACT) results, I am hopeful that we will be stimulated to put in the effort it requires to collaborate in order to truly understand how to manage this highly morbid disease. I believe all physicians want to do the right thing; however, first we have to define “the right thing” and guidelines that are inherently fraught with significant uncertainties contribute to our clouded judgement. Opinion developed through limited experience does not equate to expert opinion. Siddhartha Mukherjee, MD, DPhil, probably said it best in his book, The Emperor of All Maladies, “In God we trust. All others [must] bring data.”
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