ONCOLOGY Vol 18 No 2

Dr. Paul Sugarbaker’s reviewon management of the peritonealsurface component ofgastrointestinal cancer represents alifetime of experience with an aggressivetherapeutic approach to patientshistorically considered poor surgicalcandidates. This strategy combinestumor-directed peritoneal stripping(peritonectomy) and major abdominalvisceral organ resection, with“heated intraoperative intraperitonealchemotherapy” followed by “earlypostoperative intraperitoneal chemotherapy,”to improve outcome in patientswith seemingly fatal disease.The manuscript is thorough, informative,and reasonable. It provides historicalbackground, a discussion of thepathophysiology of peritoneal carcinomatosis,a rationale for pursuing thisapproach, a description of surgical technique,drug administration, and patientselectioncriteria, and a discussion ofselected results in the literature. Morbidity,mortality, and ethical considerationsare also briefly mentioned.

Dr. Beyer provides an insightful and balanced approach tothe indications for salvageprostate brachytherapy after externalbeamradiotherapy failure. As hepoints out, the challenge for the cliniciancontemplating local salvage therapyto address biochemical failure isto determine whether the biochemicalrelapse represents local relapse onlyor systemic disease. Local salvagetreatment in a patient with micrometastaticdisease would have no appreciableimpact on disease-free survivaland is more likely to be associatedwith significant potential morbidity.Unfortunately, with the current lackof reliable molecular markers or sensitiveimaging modalities, it is impossibleto determine with certainty thesource of a biochemical relapse inmost settings.

The success of the National SurgicalAdjuvant Breast and BowelProject (NSABP) trial P-01at showing that we now have an effectivemeans to prevent breast cancerposes larger and more seriousquestions: Who should receivechemoprevention, and at what pointin life should this occur? The designof the P-01 study allowed many womento enroll who, according to Gailmodel calculations, were at a less than 1% per year risk of subsequent breastcancer during the expected 5-yeartreatment period. These lower-risk individualsseemed to have less benefitthan those patients at much higherrisk. Other similar prevention studiesseem to confirm this observation.

Dr. Beyer has presented a thoroughreview of the current literatureon salvage implanttherapy following external-beamtherapy failure. Although the reviewpresents the available data clearly, Iwould characterize the data as preliminaryand suspect. I would questionconclusions drawn from these studiesand would especially question guidelinesfor patient selection based onthese conclusions. It will be necessaryto improve staging at recurrence, improvepathology postradiation, andimprove postimplant dosimetry beforewe can define the appropriate candidatefor salvage therapy.

Until recently, peritoneal carcinomatosis was a universally fatalmanifestation of gastrointestinal cancer. However, two innovations intreatment have improved outcome for these patients. The new surgicalinterventions are collectively referred to as peritonectomy procedures.During the peritonectomy, all visible cancer is removed in an attemptto leave the patient with only microscopic residual disease. Perioperativeintraperitoneal chemotherapy, the second innovation, is employed toeradicate small-volume residual disease. The intraperitoneal chemotherapyis administered intraoperatively with moderate hyperthermia.Part 1 of this two-part article, which appeared in the January issue,described the natural history of gastrointestinal cancer with carcinomatosis,the patterns of dissemination within the peritoneal cavity, andthe benefits and limitations of peritoneal chemotherapy. Peritonectomyprocedures were also defined and described. Part 2 discusses the mechanicsof delivering perioperative intraperitoneal chemotherapy andthe clinical assessments used to select patients who will benefit fromcombined treatment. The results of combined treatment as they vary inmucinous and nonmucinous tumors are also discussed.

Dr. Newman has written a comprehensiveand judicious reviewon the highly topical subjectof ductal lavage, and is to becongratulated. We would like to giveparticular emphasis to several of theissues she raises.

No American surgeon has thesame breadth of experiencewith extensive peritoneal resectionas Dr. Paul Sugarbaker. Moreover,only a few clinicians worldwidehave the same level of experiencewith intraperitoneal chemotherapy fora variety of intraperitoneal cancers,particularly after peritoneal resection.[1] The value of these therapiesis unquestionable in patients with lowgradetumors confined to the peritonealcavity. A number of patientstreated in this fashion show no evidenceof recurrent disease a decadeor more posttreatment.

Dr. Paul H. Sugarbaker hasspent most of his surgical oncologycareer researching andtreating patients with peritoneal surfacemalignancies. His participationin the treatment of 385 patients withappendiceal malignancy over a 15-year period is probably the largestsuch experience ever reported.[1] Dr. Sugarbaker has demonstrated that inpatients with peritoneal carcinomatosisfrom gastrointestinal malignancies,the best treatment results are associatedwith mucinous epithelial malignancyof the appendix.

The options available for patients with recurrent prostate cancerare limited. Men who have failed external-beam irradiation as the primarytreatment are rarely considered for potentially curative salvagetherapy. Traditionally, only palliative treatments have been offered withhormonal intervention or simple observation. A significant percentageof these patients have only locally recurrent cancer and are thus candidatesfor curative salvage therapy. Permanent brachytherapy withiodine-125 or palladium-103 has been used in an attempt to eradicatethe remaining prostate cancer and prevent the need for additional intervention.It is critical in this population to identify patients most likelyto have distant metastases or who are unlikely to suffer death or morbidityfrom their recurrence, in order to avoid potential treatmentmorbidity in those unlikely to benefit from any intervention. Followingsalvage brachytherapy, up to 98% of these cancers may be locally controlled,and 5-year freedom from second relapse is approximately 50%.With careful case selection, relapse-free rates up to 83% may beachieved. A schema is presented, suggesting that it may be possible toidentify the patients most likely to benefit from salvage treatment basedon prostate-specific antigen (PSA) kinetics and other features. Suchfeatures include histologically confirmed local recurrence, clinical andradiologic evidence of no distant disease, adequate urinary function,age, and overall health indicative of at least a 5- to 10-year life expectancy,prolonged disease-free interval (> 2 years), slow PSA doublingtime, Gleason sum ≤ 6, and PSA < 10 ng/mL.

Ductal lavage is a procedure that can improve the stratification ofwomen with clinical evidence of increased breast cancer risk by thecytologic detection of atypia. The relative risk of future breast cancerin women harboring atypia is approximately 3 to 5, as demonstrated instudies of women harboring atypia within direct nipple aspirates, fineneedleaspiration biopsies, and histopathology from surgical specimens.It is intuitively reasonable and biologically plausible that atypia detectedin ductal lavage specimens would be associated with a comparablemeasure of association; however, documentation of this assumptionawaits maturation of prospectively accumulated data. The technologyof the ductal lavage procedure is also a promising translational researchtool, because of the relatively substantial yield of ductal cellularmaterial for analysis via a minimally invasive technique.

Dr. Beyer has done a good jobof summarizing the issuesconcerning the use of brachytherapyas a salvage modality to treatradiation therapy failures. This willbecome an issue of greater importanceas we continue to diagnose andtreat younger and younger patientswith prostate cancer. This trend canbe primarily attributed to the successof prostate-specific antigen (PSA)screening. With younger patients optingfor radiation treatment, the numberof patients at potential risk forfailure and hence potential candidatesfor salvage brachytherapy will increase.This, coupled with the stagemigration toward early-stage, lower-PSA disease, may result in an increasingpopulation of patients with perhapsmore curable recurrent disease.