Primum Non Nocere: Of Course! But How?

Abstract

TO THE EDITOR: “Primum non nocere” stands for nonmaleficence in the Hippocratic Corpus, meaning “first, do no harm.” Colleagues who favor active surveillance for all patients with stage I testicular cancer consider adjuvant chemotherapy a potentially harmful and unnecessary intervention. However, the “surveillance for all” recommendation may infringe on patient autonomy and prove harmful. Adjuvant chemotherapy is, with few exceptions, well tolerated and without relevant long-term toxicities. Salvage treatment for relapsing patients, on the other hand, causes acute and long-term toxicities in a dose-dependent manner. Therefore, the fear of potential long-term effects of adjuvant chemotherapy seems disproportionate to the real and established toxicities after three to four cycles of bleomycin, etoposide, and cisplatin, including additional postchemotherapy RPLND in 26% of nonseminoma patients. Recently, Vidal et al published their article “Long-Term Outcome of Patients With Clinical Stage I High-Risk Nonseminomatous Germ Cell Tumors 15 Years After One Adjuvant Cycle of Bleomycin, Etoposide and Cisplatin Chemotherapy” in Annals of Oncology, in which essentially no relevant toxicity was reported. The editorial “Primum Non Nocere. Do We Harm Stage I Testicular Cancer Patients Less by Applying Adjuvant Chemotherapy Than by Failing to Present This Option?” hailed this report. Primum non nocere is thereby embraced both by the proponents of a risk-based management as well as by those advocating active surveillance for all patients with stage I testicular cancer. Both sides consider unnecessary treatment as the potential harm, identifying either adjuvant or salvage chemotherapy as the culprit. According the Spanish Germ Cell Group, a patient with a 6-cm testicular seminoma invading the rete testis and vasculature, like the one discussed by Vaughn, has a 40% risk of micrometastases. Typically, such men vote for adjuvant treatment, when counseled by proponents of a risk-based strategy like us. The majority of patients whose outcomes were published by Kollmannsberger et al were managed by the Swedish and Norwegian Testicular Cancer Group with a risk-based approach in which low-risk patients were selected for surveillance. Unfortunately, the Oncology Grand Rounds article appears biased in favor of active surveillance: Stating that “only 13% of 1,344 patients with CS I seminoma relapsed” while failing to mention the selection bias by including predominantly low-risk patients renders these numbers not representative for high-risk patients. Merely pointing to a lack of publications on long-term toxicities 20 to 30 years after carboplatin (while confirming their absence within 9 years) might cause patients to refrain from this “potentially harmful” treatment. This evasive approach appears, in light of the considerable toxicities after salvage treatment, questionable and potentially more harmful.