Watkin, Nick

Zusammenfassung Hintergrund Aktuell wurde mit dem Tetrafecta-Score das erste Instrument zur Beurteilung der Behandlungsqualität in der chirurgischen Primärtherapie des Peniskarzinoms (PECa) publiziert. Eine externe wissenschaftliche Auseinandersetzung mit den ihn definierenden Einzelkriterien steht bislang noch aus und bildet das Studienziel. Material und Methode Es wurde eine internationale Arbeitsgruppe bestehend aus 12 Urologen und einem Onkologen mit klinischer und akademisch-wissenschaftlicher Expertise auf dem Gebiet des Peniskarzinoms gegründet. In einem modifizierten vierstufigen Delphi-Prozess wurden unter Einbeziehung der Tetrafecta-Kriterien insgesamt 13 Kriterien für PECa-Patienten in den klinischen AJCC-Stadien 1–4 (T1–3N0–3, aber M0) definiert, von denen in einer geheimen Abstimmung jeder der Experten 5 auswählen musste, um dadurch einen individuellen Pentafecta-Score zu generieren. Anschließend wurde das Rating der Experten aggregiert ausgewertet und dadurch ein finaler Pentafecta-Score gebildet. Ergebnisse Keines der ursprünglichen Tetrafecta-Kriterien wurde in den finalen Pentafecta-Score übernommen, der sich aus den folgenden Kriterien zusammensetzt: 1.) Organerhalt, sofern immer möglich (≤T2), jedoch stets unter Wahrung eines negativen chirurgischen Schnittrandes, 2.) beidseitige inguinale Lymphadenektomie (ILAE) ab pT1G2N0, 3.) perioperative Chemotherapie sollte erfolgen, sofern durch die Leitlinien indiziert, 4.) ILAE sollte, sofern indiziert, in einem zeitlichen Abstand von maximal 3 Monaten zur Primärtumorresektion erfolgen und 5.) die behandelnde Klinik sollte im Minimum 15 chirurgische Primärtherapien bei PECa-Patienten durchführen. Nur 7 der 13 Experten (54%) zeigten eine starke Korrelation ihres individuellen mit dem finalen Pentafecta-Score (rsp >0.60). Schlussfolgerung Auf der Basis eines moderierten Abstimmungsprozesses unter internationalen PECa-Experten wurde ein Pentafecta-Score als Qualitätssicherungs-Instrument für die chirurgische Primärtherapie gebildet, der nun anhand von patientenrelevanten und patientenberichteten Endpunkten zu validieren ist.

We read with great interest the manuscript by Brassetti et al. recently published in your journal and hope it will encourage discussion and debate around the optimization of the surgical management of patients with penile cancer (PECa) [...]

TPS7 Background: Penis cancer is a rare but potentially fatal disease. A limited body of evidence exists on which to base the majority of management decisions for patients with regional nodal metastases. Five-year survival for patients with a single involved inguinal lymph node treated with surgery alone is approximately 80%, whilst it ranges from 0 to 12% for patients with pelvic node involvement (N3). Additional strategies are required for the management regionally-advanced disease. InPACT (NCT02305654) aims to determine prospectively the relative benefits and sequencing of surgery, chemotherapy, and chemoradiotherapy in the management of patients with penis cancer who present with palpable or radiologically evident inguinal lymph node metastases. InPACT addresses the following questions: Is there a role for neoadjuvant therapy and, if so, which of the two options (chemotherapy or chemoradiotherapy) before surgery gives superior outcomes? Among patients whose inguinal node histology predicts a high risk of recurrence, does prophylactic pelvic lymph node dissection (PLND) plus chemoradiation to the inguinal and pelvic fields improve survival compared to chemoradiation alone? Methods: A Bayesian trial design aims to include a wide population of patients and incorporates two randomisations: InPACT-neoadjuvant and InPACT-pelvis. Participants are stratified by disease burden (extent of nodal involvement), by the presence or absence of high-risk radiological features, and by GFR. Participants with high disease burden where neoadjuvant treatment is thought to be indicated are randomised to neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy. Participants with intermediate disease burden are randomised to one of 3 arms: Surgery alone or neoadjuvant chemoradiotherapy followed by surgery, or neoadjuvant chemotherapy prior to surgery. Participants in the low-burden group proceed directly to surgery. Participants with postoperative inguinal node pathology that shows high-risk features may then proceed to InPACT-pelvis where randomisation is between adjuvant chemoradiotherapy ± PLND for those not previously treated with chemoradiotherapy & between PLND & observation for those previously treated with neoadjuvant chemoradiotherapy. The study aims to recruit 200 participants. The primary outcome measure is overall survival, with secondary outcome measures of disease-specific survival, disease-free survival, and freedom from locoregional recurrence and distant metastasis. Feasibility, toxicity, the type/extent of surgical complications, and quality of life will be assessed as secondary endpoints for all the InPACT treatment arms. To October 2021, 65 participants have been recruited with centres open in the UK, US and Canada. Clinical trial information: NCT02305654.

Objectives To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM. Patients and Methods The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk‐calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m‐R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts. Results Positive surgical margins, pN 3 , and ILNM ratio were associated with higher recurrence rate. The 2‐year OS rates were lower for patients with high (>37%) and intermediate (19–37%) compared to low (<19%) 24m‐R risk of recurrence, for both the development (43% and 58% vs 83%, P < 0.001) and validation cohort (44% and 50% vs 85%, P < 0.001). Results were confirmed in the subgroup of patients who did not receive adjuvant treatment ( P < 0.001), but not in patients who did receive adjuvant treatments in both the development and validation cohorts ( P > 0.1). Conclusion Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.