{'fraction_non_alphanumeric': 0.02531239987183595, 'fraction_numerical': 0.005607177186799103, 'mean_word_length': 5.199602780536246, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
A structured approach to uncommon cancers: what should a clinician do?

In this issue of Annals of Oncology, Pecuchet et al. [1] have produced an elegant, original paper describing an innovative approach to the management of metastatic collecting duct carcinoma, using bevacizumab, gemcitabine and a platinum complex. They have shown surprising anticancer activity, which appears to have been sustained. They have addressed the usual concerns about case selection bias, positive response bias and pathology review of an uncommon tumor, and thus, this regimen certainly will bear confirmatory testing in other structured trials, especially as this triplet really does seem to give a different result from the more conventional gemcitabine–cisplatin combination or the established MVAC regimen (notwithstanding the absence of level 1 data at this time). The editorial review of this manuscript raised an important generic question, viz. what should a clinician do when approaching a patient with a truly uncommon or rare tumor? Using a cut-off figure of 15 new cases/100 000 of population per year as a definition for ‘rare cancers’, Greenlee et al. [2] have suggested that these tumors cumulatively account for around 25% of incident cases in the United States. This figure seems inflated to me, because of their cut-off value, especially as I do not view testicular cancer as a rare tumor (yet it has an incidence of 6.8/100 000 males per year). Nonetheless, Greenlee et al. make an important point—rare tumors cumulatively do constitute a significant proportion of the total cancers presenting, yet we have remarkably little information available to guide management, when compared with the common tumors that arise in breast, lung, prostate, colon, pancreas and bladder. A similar situation appears to apply to oncology practice in Europe, in a report using a cut-off of less than six new cases/100 000 of population per year, with the accompanying suggestion that outcomes are worse for the patients with rare tumors [3]. Of importance, there is masking of some rare situations—large population surveys do not address the problems presented by rare subtypes of common malignancies (e.g. small-cell prostate cancer, collecting duct carcinoma of kidney and many others), and the literature often fails to address atypical consequences of malignancy, such as the gene-associated endocrine syndromes [4]. Because of the rarity of many of these groups of cases, there is remarkably little useful information available to the clinician regarding optimal approaches to diagnosis and management. As a result, it has been suggested that there should be more publication of small case series or even isolated case reports, a view with which I strongly disagree—unvalidated anecdotes without pathology and staging review and adequate follow-up will provide little useful information to provide a reliable guide to appropriate and optimal care for these patients, and is likely to be heavily influenced by the recent trend towards open-access publication. Equally important, one should not forget the needs of patients and their families, when faced with these rare tumors— it is much more challenging for them to secure the information that they need, and this adds to their anxiety and fear, especially when the oncologist indicates lack of certainty and/or experience with the specific condition. Unfortunately, in their anxiety, such patients will often turn to the internet, and unquestioningly be guided by advertorials or anecdotes that are dominated by rhetoric rather than fact. Attempts have been made to help with the problem by producing two definitive texts—four editions of Textbook of Uncommon Cancer [5] and the French language publication, Tumeurs Malignes Rares [6], both of which provide useful information, but have not been able to cover all relevant topics in detail needed by the clinician faced with every complex and rare condition. Increasingly, the standard oncology texts are beginning to address the more interesting or therapeutically responsive rare cancers, but also fall short. There is no ‘standard’ approach to the management of uncommon cancers, although I believe that one can set a reasonable and safe structure to assist in management (Table 1). In my view, the most important first step is to secure histological review by an expert tumor pathologist. In my referral practice, it is quite common for a diagnosis of ‘rare cancer’ to be overturned by an expert—for example, the diagnosis of smallcell prostate cancer (absent neuroendocrine serological or immunohistochemical markers) often is actually a Gleason’s 5 + 5 (undifferentiated) adenocarcinoma, which requires a very different pattern of care. Thus, I usually arrange for histological review before expressing an opinion or seeing the patient. Similarly, in the context of an uncommon presentation or an uncommon tumor type, early review of staging investigations at a center of excellence is usually worthwhile. The next step really depends on the clinician’s preference. It seems perfectly reasonable for the clinician with available time to review what is known in the literature—my own preference is to consult Textbook of Uncommon Cancer, Tumeurs Malignes Rares (if one can read French) or one of the standard textbooks (hoping to find a section on the relevant uncommon tumor type), and I also will use PUB MED, with appropriate key words, to ascertain what is known about the specific tumor. Unfortunately, much of the PUB MED information is dominated by isolated case reports, often with a gratuitous review of the literature, which is often produced by someone who is NOT an expert, and compounded by data recycling [7]. An important cautionary note is to beware of the isolated case report—these are often written by relatively junior or inexperienced clinicians, and are marred by absence of expert histological review or adequate follow-up; furthermore, an isolated case report is really only an anecdote, and hardly constitutes the basis for placing a patient at risk for iatrogenic toxicity. Furthermore, many editorial policies focus against the publication of negative case reports, thus prejudicing overall editorials Annals of Oncology