Global Society of Rare GU Tumors 2020

GSRGT 2020: The Need For Perioperative Management Strategies: The Role of Radiotherapy

(Urotoday.com) The Global Society of Rare Genitourinary Tumors inaugural virtual summit included a presentation by Dr. Juanita Crook discussing the role of radiotherapy in the perioperative treatment of patients with penile carcinoma. As Dr. Crook notes, the main clinical problem is clinical node-positive penile cancer. Due to the low prevalence of penile cancer, clinical trials have not been performed to determine the optimum combination of surgery, radiotherapy, and chemotherapy. Additionally, there is no data available for contemporary radiation technology and chemo-radiotherapy techniques. Without good evidence, surgical therapy is regarded as the ‘standard of care’ for these patients. 


Penile cancer is a rare malignancy with a <1:100,000 incidence in western civilization. The majority of cases are squamous cell carcinoma with a dual pathway of chronic inflammation and human papillomavirus (40-50%). Dr. Crook notes that there are radio-responsive and radio-curable cancers, including head and neck carcinoma, cervical cancer, anal cancer, and vulvar cancer. There is consistent evidence across SCC sites (cervical, vulvar, anal, head/neck) that combination chemoradiotherapy is superior to radiotherapy alone in the neoadjuvant or stand-alone treatment setting. Post-operative radiotherapy is also a well-established standard across SCC sites for patients with multiple nodes or extracapsular spread. Finally, an HPV etiology in these sites is associated with better disease-specific survival and increased responsiveness to chemoradiotherapy and radiotherapy.            

To assess the relationship between HPV status and chemoradiotherapy in the locoregional control of penile cancer, Yuan and colleagues identified 51 patients (1999-2016) of which patients were primarily HPV-negative (n = 28, 55%), and pathologic node-positive (55%) [1]. Over a median follow-up of 36.6 months, the 2 year locoregional control rate was 54%. Lymph node-positive patients had a significantly lower 2 year locoregional control rate (37 vs. 81%, p = 0.002), and in the subgroup analysis of lymph node-positive patients (n = 28), there was a locoregional control benefit associated with the addition of chemoradiotherapy (HR 0.19, 95% CI 0.05-0.70) and HPV-positive disease (HR 0.18, 95% CI 0.039-0.80).

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Dr. Crook highlights that it is important to look at the vulvar cancer literature to potentially gain insights into the management of penile cancer. Indeed, vulvar squamous cell carcinoma is also associated with chronic inflammation and HPV, as well as having similar nodal drainage patterns to penile cancer. Vulvar cancer has many cooperative studies to establish management, noting that for locoregional vulvar cancer guidelines state that in countries where radiation therapy is not available, neoadjuvant chemotherapy could be considered a neoadjuvant option. To assess the role of adjuvant radiotherapy, the GOG 37 phase III trial randomized 114 patients that had undergone a radical vulvectomy/bilateral inguinal lymph node dissection to either pelvic lymph node dissection versus groin plus pelvic radiotherapy. This trial found that there was a 14% increase in 2-year survival (68% vs 54%, p=0.02) for patients in the radiotherapy arm, and if two or more lymph nodes were involved, 2-year survival was 26% improved (63% vs 37%, p=0.02). The GOG 205 trial was a phase 2 trial of radiotherapy plus weekly cisplatin chemotherapy for locally advanced vulvar squamous cell carcinoma. This trial included 58 patients with the surgically unresectable disease (T3-T4, N0-N3) who received 57.6 Gy of radiotherapy plus weekly cisplatin (40 mg/m2). 69% of patients completed 5 cycles, leading to a 64% response rate.

Dr. Crook highlights that there are several uncertainties with regards to radiotherapy utilization in penile cancer:

  • Neoadjuvant versus definitive?
  • Surgical tolerance after neoadjuvant chemoradiotherapy?
  • When should we use adjuvant therapy?
  • Is adjuvant chemotherapy as good as adjuvant radiotherapy?
  • Can pelvic chemoradiotherapy replace surgical pelvic lymph node dissection in patients with high-risk groins?

            Dr. Crook states that there are several primary objectives of the InPACT trial that will clarify some of the role of radiotherapy, namely (i) is there a role for neoadjuvant therapy and, if so, does chemotherapy or chemoradiotherapy produce superior outcomes (either for survival or for morbidity/quality of life)? (ii) What is the additional survival benefit of prophylactic pelvic lymph node dissection +/- chemoradiotherapy over and above that of chemoradiotherapy alone following inguinal lymph node dissection in patients at high risk of recurrence?

Dr. Crook concluded her presentation with the following take-home points:

  • Faute de mieux, for the want of better penile-specific data, clinical practice is borrowing from the established experience of other disease sites
  • Hopefully InPACT will provide guidelines on the optimal integration of surgery, radiotherapy, and chemotherapy


Presented by: Juanita Crook, MD FRCPC, Radiation Oncologist, University of British Columbia, BC Cancer Center for the Southern Interior, Kelowna, British Columbia, Canada

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md during the 1st Global Society of Rare Genitourinary Tumors Virtual Summit, December 11-12, 2020

References:
1. Yuan Z, Naghavi AO, Tang D, et al. The relationship between HPV status and chemoradiotherapy in the locoregional control of penile cancer. World J Urol2018 Sep;36(9):1431-1440. 

Related Content: 
The Relationship Between HPV Status and Chemoradiotherapy in the Locoregional Control of Penile Cancer - Beyond the Abstract 

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