Best of EAU: New advances in testicular and penile cancer

Analysis of microRNA (miRNA) expression allowed to discriminate between viable tumour, teratoma, and necrosis on post-chemotherapy retroperitoneal lymph node dissection (RPLND). A retrospective study underlined that sequential post-chemotherapy residual tumour resection is mandatory. These and other findings were presented in the Best of EAU21 session by Prof. Maarten Albersen (UZ Leuven, Belgium) [1].

Biomarker-guided therapy could reduce overtreatment with post-chemotherapy RPLND in patients with only necrosis in the specimen. Therefore, a German study aimed to identify a combination of miRNAs as potential biomarkers to differentiate between viable tumour, teratoma, and necrosis [2]. miRNA expression was analysed using quantitative real-time PCR (qRT-PCR) in post-chemotherapy RPLND tissues containing necrosis (n=16), teratoma (n=16), and viable tumour (n=16).

When comparing viable tumour versus necrosis, miR-371-3p achieved the highest fold change of 31.1 (P=0.023), whereas miR-375-5p performed best for teratoma versus necrosis with a fold change of 64.2 (P<0.001). Combining the best performing miRNAs for viable tumour and teratoma generated an area under the curve (AUC) of 0.94, with a sensitivity and specificity of almost 94% for both. Positive predictive value was 96.8 and negative predictive value was 83.3.

This study demonstrated that miR-371a-3p and miR-375-5p are potential biomarkers for the discrimination between viable tumour, teratoma, and necrosis in post-chemotherapy RPLND. These results need to be validated in serum.

Residual tumour resection in metastatic germ cell tumour

In patients with metastatic germ cell tumours, post-chemotherapy residual tumour resection is a crucial part of treatment. Surgery should commence at the site with the highest volume of residual disease; concordance has been shown to be up to 90%.

A retrospective study analysed histological concordance between thoracic and retroperitoneal lesions in 54 patients who had undergone retroperitoneal and thoracic residual tumour resection after first-line as well as salvage chemotherapy [3].

Most patients (91%) first underwent retroperitoneal residual tumour resection. The results showed that histology of retroperitoneal and thoracic residual tumour resection matched in 35 patients (65%) and was discordant in the other 19 patients (35%). Of 21 patients with retroperitoneal necrosis, 7 (33%) showed vital cancer or teratoma in the thorax. First-line chemotherapy resulted in a discordance rate of 29%, which increased after salvage chemotherapy to 58% (P=0.087).

This data underlines the need for sequential post-chemotherapy residual tumour resection, since discordance of histology is up to 35%. “They concluded that retroperitoneal necrosis histology did not predict for thoracic necrosis,” Prof. Albersen said. “Discordant histology was more prevalent in patients after salvage chemotherapy, which indicates that thoracic resection is needed independent of tumour volume.”

Dynamic sentinel lymph node biopsy for penile cancer

Dynamic sentinel lymph node biopsy is routinely offered to patients presenting with >T1G2 cN0 penile cancer, that is, without palpable lymph nodes. Due to concerns about low sensitivity, dynamic sentinel lymph node biopsy is not widely used outside of centralised care systems.

A retrospective analysis of eUROGEN centres evaluated patients with intermediate-high risk cN0 penile cancer [4]. A total of 993 groins in 509 patients were studied. After a median follow-up of 62.5 months, 37 (7.27%) patients had positive histology at dynamic sentinel lymph node biopsy; 34 of them had positive histology at inguinal lymph node dissection. At dynamic sentinel lymph node biopsy, 37 (7.27%) were true positives and 3 were false negatives (0.59%). Sensitivity was 92.5% and specificity was 100%.

“Dynamic sentinel lymph node biopsy is a good staging examination in penile cancer, with a lower complication rate than inguinal lymph node dissection but a higher false-negative rate,” concluded Prof. Albersen. Sensitivity in centralised services was 92.5%. Surprisingly, only 7.27% were true positives, which would have resulted in overtreatment of 92.7% if lymph node dissection had been adopted. Despite having a higher rate of false-negative results (0.59%) compared with inguinal lymph node dissection, dynamic sentinel lymph node biopsy was found to be a well-balanced and accurate staging method for penile cancer.

Triple therapy for advanced penile cancer

Although neo-adjuvant platinum-based chemotherapy combinations have been used for patients with advanced penile squamous cell carcinoma, these treatments have shown poor efficacy rates amounting to 50%. Evidence on combinatorial schedules including targeted agents and checkpoint inhibitors is limited [5].

To this end, a prospective, single-arm, open-label, phase 2 study included 10 patients (median age 55.5 years) with chemotherapy-naïve, advanced penile squamous cell carcinoma (T4 or N3, M0). Patients received toripalimab (anti-PD-1) plus nimotuzumab (anti-EGFR) on day 1 plus chemotherapy intravenously every 3 weeks for 4 courses; 8 patients received >2 courses. Neoadjuvant treatment with subsequent radical surgery was completed by 5 patients, of whom 4 achieved pathologic complete response (pCR). At least 1 treatment-related adverse event of grade 1–2 was experienced by 90% of patients, most commonly numbness of hand and foot (90%), nausea (70%), and decreased appetite (40%). There were no grade 3 or 4 adverse events.

This small cohort demonstrated that triple therapy with anti-PD-1, anti-EGFR, and chemotherapy may be promising for patients with advanced penile cancer. Only 50% of patients proceeded to surgery and pCR was relatively high. Overall response rates were not assessed. This protocol may be promising, although overall response rates are not clear and reasons for discontinuation were not disclosed.

1. Albersen M. Best of EAU: Testis/Penile cancer. EAU21 Virtual, 8–12 July 2021.
2. Nestler T. P0658, EAU21 Virtual, 8–12 July 2021.
3. Buddensieck C. P0665, EAU21 Virtual, 8–12 July 2021.
4. Pozzi E. P0667, EAU21 Virtual, 8–12 July 2021.
5. Shi Y. P0680, EAU21 Virtual, 8–12 July 2021.

 

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Posted on 31 August 2021