Perioperative use of opioids and risk of ovarian cancer recurrence and metastasis
Objective. The primary objective of this cohort study is to determine if use of opioids increases the risk of ovarian cancer recurrence and metastasis. The specific objectives are to determine whether: 1) use of IMM opioids during surgery increases the risk of cancer recurrence or metastasis when compared to NIMM opioid use, among patients undergoing general anesthesia; 2) use of postoperative IMM opioids during surgery increases the risk of cancer recurrence or metastasis when compared to NIMM opioid use, among patients undergoing general anesthesia; 3) use of postoperative IMM opioids during surgery increases the risk of cancer recurrence or metastasis when compared to NIMM opioid use, among patients undergoing general anesthesia and epidural, and 4) there is a dose and duration-response relationship between IMM and NIMM opioids at recovery room and the risk of cancer recurrence or metastasis. Knowledge that opioids may prevent cellular immune function, increase angiogenesis and promote breast tumour growth in rodents supports our hypothesis that increased preference of opioid analgesics could be related to increased risk of cancer recurrence and metastasis. Paradoxically, little research has addressed the association of opioids use and cancer recurrence or metastasis, considering that preference for opioid analgesics has increased substantially worldwide.
Method. In this nested case-control study, participants aged ? 18 years who received a first ovarian cancer surgery between 2007 and 2013 will be included in the study cohort. All eligible patients will be followed until: 1) a first cancer recurrence occurs during the study period; 2) death from any cause; 3) development of one exclusion criteria during follow-up; or 4) end of the study period, whichever comes first. The primary outcomes are the incidence of cancer recurrence and metastasis during the study period. Use of IMM or NIMM opioids during surgery and at recovery room will be assessed by chart review among all ovarian cancer patients surgery cohort. We will calculate cumulative dose and time for each participant, and assess use of opioids before and after surgery. We will assess the date of prescription, the quantity prescribed, the duration, and the daily doses also by chart review of the database. Opioids will be separated into IMM and NIMM groups. If patients use opioids before the surgery they will be classified as prevalent cases, whereas if opioids are only used after the surgery, patients will be classified as incident cases. Cox proportional hazards regression will be used to estimate the hazard rate ratios of cancer recurrence and metastases related to the use of IMM or NIMM opioids.
Significance. The results of this study will advance our understanding of the effects of opioids use (IMM and NIMM) on the risk of ovarian cancer recurrence and metastasis, including the function of their dose and duration. These results may help to reduce the risk of recurrence or metastasis in ovarian cancer, as well as in other types of cancer. Pharmacotherapy optimization can play an important role in reducing the public health impact of cancer recurrence or metastasis.
