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Commentary (Kessinger): Management of Patients With Cancer of Unknown Primary Site

Commentary (Kessinger): Management of Patients With Cancer of Unknown Primary Site

Over the past 2 decades, advances in clinical oncology have occurred at a whirlwind pace, as new surgical, diagnostic, preventive, immunotherapeutic, chemotherapeutic, radiotherapeutic, and molecular resources and techniques have become available. As one result, the death rate from cancer in the United States has decreased during the past decade.[1] Thanks to these advances, many patients have replaced feelings of hopelessness with hope for a cure.

Yet, despite these gratifying advances, 5% of cancer patients currently appearing at the doorsteps of oncologists have metastatic malignancies, the primary source of which cannot be located. The list of frustrations that oncologists presently face is a long one, and toward the top of that list is the inability, despite all of the modern resources at hand, as well as their own wisdom, to pinpoint the primary site of disease in these patients. Such patients must feel equally, or more, frustrated, wondering why their doctor cannot locate the source of their problem. For the physician, a feeling of inadequacy cannot always be suppressed as the patient hears the news and then asks the inevitable questions.

Defining the Best Possible Management Plan

Drs. Hainsworth and Greco have been interested in patients with an unknown primary tumor for many years. Yet, rather than pursuing new diagnostic techniques to locate more occult primary lesions, the authors have taken a more pragmatic approach. Acknowledging the unfortunate, present-day fact that not all primary cancers can be identified, the authors have set out to define the best possible management plan for patients with this predicament. This task, which must have seemed formidable to the authors at the outset, has been approached in a methodical manner that can now be easily applied to the clinical setting.

First, the authors have subdivided the unknown primary tumors into two categories, based on a consideration of the histologic and immunocytochemical properties of the malignancy, as well as the clinical presentation—a process that has evolved over the years as new information and techniques became available. Basically, there are two subdivisions: patients with a presumed primary site and patients with a primary site that cannot be fathomed. The first subdivision is comprised of nine categories. The second subdivision consists of patients with metastatic adenocarcinoma for which no primary site can be presumed.

For each division and subdivision, the authors have proposed management options. Some of these management approaches are empiric, based on clinical experience and intuitive thinking (given the lack of formal studies available), while others are based on the results of clinical trials.

In 1998, Oncology published the National Comprehensive Cancer Network’s guidelines for the management of occult primary tumors.[2] The complexity of the subject was well illustrated by the fact that 83 pages were dedicated to these guidelines.

Because one of the words in the title of the reviewed subject is “unknown,” it follows that some differences of opinion may exist. For example, some might wonder if women with peritoneal carcinomatosis and elevated serum CA-125 levels truly have an unknown primary site, as opposed to a primary peritoneal carcinoma.[3,4]

Points Worthy of Further Comment

As in a review of any subject, some points are more important than others and perhaps deserve some expansion in this commentary. First, the authors state that the pathologist is a very important, and often the most important, resource in cases of an unknown primary. Reviewing the case face to face with a concerned pathologist and looking at the tissue slides together, as well as brainstorming, has been very helpful to this reviewer when confirming a diagnosis of unknown primary.

Second, the authors claim that one should avoid the temptation to treat a metastatic mucin-producing adenocarcinoma of unknown primary as if it were of gastrointestinal origin. Studies, nicely described in their review, show that paclitaxel (Taxol)-based combinations can produce responses, even complete responses, and that survival beyond 1 year is a reasonable expectation, with occasional survival of 2 or 3 years in this patient population.


The current review by Hainsworth and Greco is clearly and concisely written, well referenced, and presented in a clinically useful format. By providing timely information and references on the current status of unknown primary malignancies, the authors offer a guiding light for oncologists and patients faced with a dark clinical situation. We look forward to the results of their ongoing investigations in this area.


1. Greenlee RT, Murray T, Bolden S, Wingo PA: Cancer statistics, 2000. CA Cancer J Clin 50:7-33, 2000.

2. NCCN practice guidelines for occult primary tumors. Oncology 12(11A):226-309, 1998.

3. Ozols RF, Schwarz PE, Eifel PJ: Ovarian cancer, fallopian tube carcinoma, and peritoneal carcinoma, in DeVita VT Jr, Hellman S, Rosenberg SA (eds): Cancer: Principles and Practice of Oncology, 5th ed, pp 1502-1539. Philadelphia, Lippincott-Raven , 1997.

4. Piver, MS, Jishi MF, Tsukada Y, Nava G: Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. Cancer 71:2751-2755, 1993.

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