A novel marker of nutritional status in high-risk penile cancer, "Beyond the Abstract," by Pranav Sharma, MD, and Philippe E. Spiess, MD

BERKELEY, CA (UroToday.com) - Penile cancer comprises only a small proportion of all genitourinary (GU) malignancies in the United States and other developed nations due to the common practice of circumcision, as well as overall improved hygiene. Advanced forms of penile cancer, however, can cause significant morbidity and mortality in affected patients. One of the most important prognostic factors of the disease is lymph node involvement, initially in the inguinal region and subsequently in the nodes of the true pelvis. Inguinal lymph node dissection (ILND), with or without a pelvic lymph node dissection (PLND), is therefore recommended in men with a high-risk primary penile tumor and with palpable nodes on physical examination to improve cancer-specific (CSS) and overall survival (OS). Use of advanced imaging such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) – CT can further delineate high-risk patients who may benefit from early node dissection in the setting of localized disease.

Lymph node dissection (LND) for the treatment of high-risk cases or in advanced stages of the disease still poses a significant complication risk even at high-volume, tertiary referral centers. Wound infection, wound dehiscence, flap necrosis, lymphocele, seroma formation, and chronic scrotal or lower extremity lymphedema are still common occurrences after surgery that can impair a patient’s overall quality of life. Current prognostic markers of patient fitness, such as age, Eastern Cooperative Oncology Group (ECOG) performance status, American Society of Anesthesiologists (ASA) score, and Charlson comorbidity index, as well as indices of nutritional status, such as body mass index (BMI) and preoperative albumin level, are currently ineffective in predicting which patients are more likely to experience these adverse outcomes in the postoperative setting. These measures are often subjective and unreliable, varying drastically at different time points over a relatively short period of time.

In recent years, a novel, objective, image-based marker of an individual’s cancer-related nutritional state, called sarcopenia, has emerged, and it is both reliable and reproducible. It is based on skeletal muscle area (i.e., muscle mass) at the third lumbar vertebrae (L3) on CT-based imaging, calculated in a large cohort of advanced cancer patients, with cutoff points generated based on differences in survival. It has also been reported to be a predictive tool for survival and complications in patients undergoing surgery for other GU malignancies such as with cystectomy and with urinary diversion for advanced forms of bladder cancer.

In our study, we evaluated the prognostic ability of sarcopenia in penile cancer patients undergoing ILND +/- PLND for high-risk or clinically node-positive disease. Our study population was small since a large number of patients were excluded due to lack of available preoperative imaging for analysis. Despite our smaller sample size, however, we described the superior ability of sarcopenia to predict 30-day complications after surgery compared to other known historical markers mentioned above, including use of a muscle flap for vessel coverage and surgery in a salvage setting. Sarcopenic patients also had a worse estimated mean overall survival (OS) compared to non-sarcopenic patients (32 vs 68 months) although this difference did not reach statistical significance (p=0.275) due to a small number of deaths and poor follow-up.

We feel the future of sarcopenia, however, is in its ability to be reversed prior to treatment and thus potentially improve outcomes for cancer patients. Weight-bearing exercises, vitamin administration, antioxidants, and hormone supplementation have all shown promise in reversing cancer-related skeletal muscle wasting and improving overall muscle mass. Whether this will translate into improved short-term postoperative outcomes and improved survival for penile cancer patients undergoing surgical treatment has yet to be determined and could be the focus of future randomized, prospective studies. The prevalence of sarcopenia in non-cancer patients is also largely unknown. Whether its presence and subsequent reversal may play a role in other disease states needs further investigation.

Use of multi-modal therapy also plays an important role in the treatment of advanced penile cancer, especially in the neoadjuvant setting for those men with bulky, unresectable disease or for those patients who cannot tolerate a surgical procedure. Better systemic regimens need to be established, however, to improve overall response rates and impact survival. A large, multi-national, prospective clinical trial has recently been designed and will shortly start accrual to hopefully better address this study question and provide guidance for the treatment of these men in the future. We are also currently working on additional multi-institutional studies to evaluate the impact of adjuvant chemotherapy as well as adjuvant radiation therapy on patients with positive pelvic lymph node disease after PLND in a non-metastatic setting to examine its effects on long-term survival.

Written by:
Pranav Sharma, MD, and Philippe E. Spiess, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Corresponding Author:
Philippe E. Spiess, MD, FACS, FRCS(Urol)
Associate Professor of Urologic Oncology
H. Lee Moffitt Cancer Center
12902 Magnolia Dr.
Tampa, FL 33612 USA
E-mail:

First Author:
Pranav Sharma, MD
Genitourinary Oncology Fellow
H. Lee Moffitt Cancer Center
12902 Magnolia Dr.
Tampa, FL 33612 USA
E-mail:

Sarcopenia as a predictor of complications in penile cancer patients undergoing inguinal lymph node dissection - Abstract

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