Bone is the New Primary - Daniel George

How many times has a patient with advanced prostate cancer said to you, “I have bone cancer?” 

In the past, I would smile politely and correct them by saying, “actually what you have is prostate cancer that has spread to your bones.” But, what if they are right? I mean, many of these patients have previously undergone a prostatectomy or radiation therapy, and have no evidence of local disease. Sure, the patient may have an elevated prostate-specific antigen (PSA) level, but does that alone really make this prostate cancer? 

In prostate cancer, bone is by far the most common site for this disease to recur; by some estimates 90 percent of stage IV patients have bone metastases. Statistically, these patients also have a worse prognosis than the 10 percent with lymph node metastases, furthermore suggesting that metastasis to bone sites is biologically distinct as well (1).  The process of metastasis is complex and still far from completely understood, but work by Gundem et al revealed in extraordinary detail through whole exome sequencing of 51 metastases from 10 patients with mCRPC that metastasis to metastasis spread is common and is both monoclonal and polyclonal, even within a single metastasis (2). So, why should this matter?

Over 100 years ago Stephen Paget put forward the “seed and soil” theory for cancer metastasis, which still holds true today (3). The concept is simple enough —conditions for tumor metastasis require both the seeding of a distant tissue with tumor cells as a microenvironment enriched with nutrients and supportive structures to allow these seeding cells to grow. These “soil” conditions are not universal, which is why we have seen some tumor types preferentially spread to certain organs.  Unfortunately, we have many more drugs that target the seeds (hormone therapy, chemotherapy) than the soil.  It’s time to change that.

Currently, we target the primary tumor in patients with localized disease by treating or removing this environment, but we need to think of bone and bone metastases through a similar lens. Studies are already underway to target oligometastatic disease with stereotactic radiotherapy and other approaches, used in conjunction with hormonal and chemotherapy approaches. Likewise, Radium 223 targets not only tumor cells, but supportive cells in tumors as well. This therapy alters lesions in unique and potentially permanent ways. Bisphosphonates and denosumab target osteolytic and osteoblastic cells: changing the micro-environment and affecting the rates of bone-related complications. 

This center of excellence is dedicated to highlighting the breakthrough research advancements developing in the field that alter the bone environment. In order to affect tumor spread, we are committed to changing the soil. To accomplish this, we are focused on disease progression, quality of life of patients and ultimately, the survival of those we care for with this lethal phenotype. 

Written by: Daniel J. George, MD, Medical Oncologist, Professor of Medicine, Professor in Surgery, Duke Cancer Institute, Durham, North Carolina

  1. Halabi S, et al. Meta-Analysis Evaluating the Impact of Site of Metastasis on Overall Survival in Men With Castration-Resistant Prostate Cancer.J Clin Oncol. 2016 May 10;34(14):1652-9. 
  2. Gundem G, et al. The Evolutionary History of Lethal Metastatic Prostate Cancer. Nature. 2015 April 16; 520(7547): 353–357.
  3. Langley RR and Fidler IJ. The seed and soil hypothesis revisited - the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer. 2011 June 1; 128(11): 2527–2535.