Nearly 30% of intra-abdominal malignancies present with peritoneal metastases.
Historically peritoneal metastases were considered a death knell with an average median survival of 6 months. For non-ovarian malignancies, with peritoneal metastases, the median survival, if not treated, is 6 months for colorectal cancers, 0.7 months for pancreatic cancers and 1 month for gastric cancers.
Unavoidably, this nihilistic view informs our approach to the treatment of patients with carcinomatosis. A grim prognosis is routinely administered with limited, if any, hope of effective treatment. For patients who present with a reasonable performance status, treatments offered are frequently limited to palliative systemic therapy, hopefully with an early referral to palliative care for supportive management and assistance with goals of care. For patients who present with an acute complication of carcinomatosis, hospice is often the only option offered.
However, recent advances in our understanding of carcinomatosis demonstrate that it is not a single entity with a uniformly lethal behaviour. Likewise, due to advances in surgical techniques and regional therapies, palliative systemic therapy is no longer the only treatment option available. Thus, as with most other forms of cancer, the treatment of carcinomatosis can and should be approached on an individual basis with respect to the patient, the tumour biology, and the variety of therapeutic options available.
What Constitutes Peritoneal Cancers?
There are 2 types of peritoneal carcinomatosis: Primary peritoneal cancers and metastases from other abdominal and extra abdominal organs.
Primary peritoneal cancers include the primary peritoneal adenocarcinoma, which behaves like ovarian cancer and Peritoneal Mesothelioma.
Peritoneal metastases may be the only site of metastases or may be associated with other metastases like liver and lung metastases. The common organs which metastasise to the peritoneum and abdominal cavity include appendix, ovary, colon, stomach, pancreas, gall bladder, uterus and rarely extra-abdominal organs like breast and lung.
An entity called pseudomyxoma peritonei which may range from almost benign (DPAM: diffuse peritoneal adenomucinosis) to low grade and high grade appendiceal carcinoma can present only intra-abdominally as a jelly like collection of Mucin. Traditional chemotherapy is not effective in these cases.
Evolution in Treatment Paradigms:
There has been a paradigm shift in the way peritoneal cancers are treated. Two points are important to be noted at this juncture.
Firstly, “not all peritoneal carcinomatosis are created equal”. They differ in their behaviour across different tumour types as well as within the same tumour type. The prognosis associated with peritoneal dissemination of an indolent mucinous neoplasm of the appendix is typically measured in years, whereas the prognosis for peritoneal carcinomatosis from gastric cancer may be measured in weeks.1,2 Similarly, the expected prognosis of a patient with T4 signet ring cell cancer of the colon with diffuse military seeding of the peritoneum is much less than that of a patient with T4, lymph node- negative, low-grade colon cancer with a limited number of discrete, resectable tumor nodules within the peritoneum. Secondly, cancer or metastases localised only to the peritoneum, without spread to lungs, liver or any other extra-abdominal location is considered as local disease. As such directed therapies can achieve complete removal of disease and chances of a cure.
The therapies which have brought about this change can be grouped as follows
a. Curative treatment options
b. Palliative treatment options &
c. Bridging treatment options
This includes mainly a) CytoReductive Surgery (CRS) and b) Heated Intra PEritoneal Chemotherapy (HIPEC). The rationale behind this approach is to achieve a macroscopically complete cytoreduction of the carcinomatosis (no residual tumor measuring greater than 0.25-cm thick) and then treat any residual microscopic disease with high concentration, hyperthermic chemotherapy applied directly into the peritoneal cavity. Achieving a complete cytoreduction involves major abdominal surgery. Based on the volume and distribution of the carcinomatosis, as well as the “invasiveness” of the peritoneal implants, achieving a complete cytoreduction may involve major peritoneal stripping, multivisceral resections (including the omentum, large and small bowel, stomach, spleen, gallbladder, uterus and ovaries, pancreas, ureters, and bladder), and the creation of temporary or permanent stomas. Upon completion of the cytoreduction, HIPEC is typically administered for 30 to 120 minutes (depending on the preference of the surgical oncologist and the type of chemotherapy used). A comprehensive review of reported results from more than 20 CRS/HIPEC centers since 2003 shows major morbidity rates of 0% to 50% and mortality rates ranging between 0% to 6% at high-volume centers. These rates are now consistent with other major abdominal cancer operations such as pancreaticoduodenectomy and esophagogastrectomy. The survival advantage with CRS+HIPEC in various cancers is shown in the table number 1.
Palliative treatment options:
These include basically management of symptoms and use of traditional chemotherapy where CRS+HIPEC and/or the bridging treatment options are not possible. These include drugs like octreotide, surgery for small bowel obstruction wherever possible and improvement of nutrition for improving quality of life.
Bridging treatment options: These basically includes options like PIPAC which were started as palliative treatment options but which have shown to have tremendous effects in peritoneal metastases and these patients can then undergo CRS+HIPEC at a later date, thus converting a potentially palliative situation into a curative one.
a) PIPAC: PIPAC stands for Pressurised Intra Peritoneal Aerosolised Chemotherapy. This is a revolutionary procedure. In this procedure, standard liquid chemotherapy is used in 1/10th of the dose which is used in intravenous chemotherapy; and through a special device is converted into an aerosolised form of chemotherapy. Unlike HIPEC, it is not done with CRS. It is a standalone procedure which is repeated every 8 weeks till there is complete response or patient can tolerate.
The following are the advantages of PIPAC:
1. Only 1/10th the dose of standard chemotherapy is used. So there are no side effects like that of traditional chemotherapy. In over 3000 PIPAC instillations worldwide there was no hair loss, no renal or haematological complications. The only complications were nausea, malaise, occasional fever and wound infections.
2. It can be used in all types of Peritoneal cancers unlike HIPEC which is best effective in Ovary, colon, stomach, mesothelioma and pseudomyxoma peritonei. In these cancers,
PIPAC can reduce the burden of disease and make the patient fit for HIPEC. In other peritoneal metastases like that from Pancreas, Gall bladder and breast it significantly reduces the ascites and intestinal obstruction rates, which drastically improves the patients’ quality of life.
3. It is a day care procedure and patient can be discharged the same night or next day morning.
The 2 disadvantages are:
1. It is a surgical procedure done laparoscopically and under general anaesthesia &
2. It is slightly costly. The present rate in India is around 2lakh rupees per cycle.
However PIPAC can be used in all patients who have received multiple lines of chemotherapy and in these heavily pre-treated patients too, the survival benefit ranges from 3 months to 2 years.
Image courtesy : http://www.capnomed.de/en/pipac.htm
b) NIPS & EPIC: NIPS stands for Neoadjuvant Intra Peritoneal and Systemic Chemotherapy. This has been shown to be effective in Gastric cancers with peritoneal metastases and peritoneal cytology positive gastric cancers. These were traditionally relegated to palliative chemotherapy. Reduction in the volume of disease after NIPS can actually allow a radical curative surgery to be done at a later stage.
EPIC stands for Early Post-operative chemotherapy. This is given after the end of cytoreductive surgery and HIPEC. This has found to have added benefits in ovarian and colorectal cancers and pseudomyxoma. A port is implanted in the abdominal wall and chemotherapy is given from day 1 to 5. It is kept intrabdominally for 23 hours and drained for 1 hour before the next instillation.
c) Laparoscopic Debulking: This is usually done in cases of pseudomyxoma peritonei.
Occasionally the amount of mucin in the abdomen is so high that the patient is not fit for prolonged anaesthesia and radical surgery or is grossly malnourished to tolerate a supramajor procedure like CRS+HIPEC. In this cases, the mucin is evacuated by laparoscopic technique. The patient is then made fit for surgery and CRS+HIPEC is carried out at a later date. Now with the advent of PIPAC, in cases unfit for HIPEC, laparoscopic debulking with PIPAC can give a good quality of life and prolonged survival to the patients.
Thus through our understanding of the peritoneal-blood barrier, the peritoneal cavity offers an additional route for new, carcinomatosis-specific treatments. A variety of clinical trials now abound for a group of patients who were once “written off.” Peritoneal carcinomatosis is no longer an absolute death sentence. Modern, multimodality approaches to treatment (including systemic chemotherapy, cytoreductive surgery, and intraperitoneal chemotherapy) have significantly improved outcomes for selected patients with peritoneal carcinomatosis. However it should be remembered that outcomes for patients with peritoneal carcinomatosis still depend largely on the origin and histology of the tumor. A multidisciplinary team approach, including early palliative care, is essential to the comprehensive management of peritoneal carcinomatosis.
Courtesy: By Dr Ninad Katdare, Consultant- Surgical Oncology, Global Hospitals, Mumbai
The Times of India