ONCOLOGY Vol 19 No 10

Dr. Khatcheressian and colleagueshave nicely reviewedboth barriers to palliative andsupportive care and remedies.

Malignant pleural mesothelioma(MPM) is an invasivelocally aggressive tumorthat is nearly always fatal. Historically,treatments resulting in durable controlhave seemed unobtainable andfostered a somewhat fatalistic managementapproach. Until recently, nonovel therapies had emerged that offeredreal hope for improvement inthe poor median overall and progression-free survival. In this issue ofONCOLOGY, Dr Antman and colleaguesprovide an overview of theepidemiology, natural history, andmanagement strategies for malignantmesothelioma, with an emphasis onMPM.[1]

High-grade urothelial cancer ofthe bladder is not only relativelycommon but unfortunately,is frequently lethal. These tumorsare often diagnosed when thetumors have already invaded the wallof the bladder. Even when they arediagnosed at a time when they areconfined to the mucosa or lamina propria,patients may not respond to abladder-preservation approach. Oftena radical cystectomy with urinary diversionis either not offered at all or notconsidered until the cancer has invadeddeep into the muscularis propria andlocal treatment fails.

Mesotheliomas are uncommon in the United States, with an incidenceof about 3,000 new cases per year (or a risk of about 11 per million Americansper year). Incidence and mortality, however, are probably underestimated.Most are associated with asbestos, although some have arisen inports of prior radiation, and a reported association with simian virus (SV)40remains controversial. About 85% of mesotheliomas arise in the pleura,about 9% in the peritoneum, and a small percentage in the pericardiumor tunica vaginalis testis. The histology of about half of mesotheliomas isepithelial (tubular papillary), with the remainder sarcomatous or mixed.Multicystic mesotheliomas and well-differentiated papillary mesotheliomasare associated with long survival in the absence of treatmentand should be excluded from clinical trials intended for the usual rapidlylethal histologic variants of the disease. The median survival isunder a year, although longer median survivals for selected patients,particularly those with epithelial histology, have been reported in somecombined-modality studies. Recent randomized trials have shown significantimprovement in time to progression and survival for the additionof new antifolates to platinum-based chemotherapy.

The management of ovarian cancer entails a complex blend of medicaland surgical interventions. Managing patients with recurrent ovariancancer increases the complexity of therapies and adds palliative interventions.The presence of recurrent ovarian cancer is both emotionally andphysically taxing for patients as well as their caregivers. With an increasinglyinformed patient population, a balance must be achieved betweeneasily accessible information enabling patients to know that they nowhave an incurable disease and support for their hopes and desires to stillovercome their cancer. The decision tree in the management of recurrentovarian cancer blends many different factors. This discussion will separatethose factors as if they are pure elements. We will address managementbased on response to primary therapy and time to recurrence, thelocation of recurrence, symptoms of recurrence, the patient’s histopathology,and the patient’s primary stage as it relates to the extent of diseasepresent at the start of chemotherapy.

In their article, Drs. Michener andBelinson make the case for treatingrecurrent ovarian cancer as achronic disease, with limiting morbidityand providing palliation of symptomstheir major goals. A review ofrecent literature would support their contention and management strategy.The cure rate for patients with recurrentovarian cancer is < 5%, and theaverage patient in the United Statesreceives more than five separate regimensof chemotherapy for recurrentdisease. Previous attempts at aggressivetreatment for recurrent disease haveshown, at best, very modest benefitwith significant expense and morbidity.What we are left with is a strategy oftrying to determine which patients maybenefit from aggressive salvage therapyand which are better managed witha chronic palliative attempt.

The Michener/Belinson articledeals not so much with what isnew in the treatment of ovariancancer, but with the changing managementparadigm. The authorscorrectly point out that one cannotexpect to offer curative options inovarian cancer patients who recur.Consequently, in planning therapy,the focus should be on the ability toprovide a lifelong strategy to controlthe disease through maintenance therapy.After first-line chemotherapy,complete responders have reasonablylong remissions in the absence of anyintervening therapies, but this is notlikely to be the case with recurrentdisease. In fact, Markman et al[1] havestressed that remissions followingtreatment for recurrence are neverlonger than the preceding ones.

Despite major advances in cancerbiology and therapeutics,cancer and its treatment continueto cause devastating suffering,not only for the more than half a millionpatients who will die this yearfrom cancer, but also for many ofthose who will be successfully treated.[1] Symptom burden has a profoundimpact on the quality of life ofcancer patients across all stages of disease.Routine screening of ambulatorycancer patients identifies an average of7 to 10 distressing physical and psychologicalsymptoms per patient.[2]Even patients with a good performancestatus have a median of nine or moresymptoms.[3,4] Not surprisingly, theseverity and burden of symptoms nearthe end of life is even greater.[4]

Twenty years of research in controlling symptoms such as pain andnausea have shown persistent suboptimal performance by the US oncologysystem. The data suggest that some of the tools of palliative careprograms can improve physical symptoms of seriously ill patients at acost society can afford. To fix these problems will require recognitionof the symptoms or concerns, a system such as an algorithm or careplan for addressing each, measurement of the change, and accountabilityfor the change. Symptom assessment scales such as the EdmontonSymptom Assessment Scale or Rotterdam Symptom Check List work tomake symptoms manifest. Listing symptoms on a problem list is a necessarystep in addressing them. Physical symptoms such as pain can beimproved by use of computer prompts, algorithms, dedicated staff time,team management, or combinations of these strategies. Less concreteproblems such as medically appropriate goal-setting, integrating palliativecare into anticancer care sooner, and informing patients aboutthe benefits and risks of chemotherapy near the end of life require morecomplex solutions. We review what is known about symptom control inoncology, how and why some programs do better, and make suggestionsfor practice. Finally, we suggest a practical plan for using symptomassessment scales, listing the problems, and managing them accordingto algorithms or other predetermined plans.

Bladder cancer is the fifth most common cancer diagnosed in theUnited States. Prognosis for this disease is dependent on both tumorstage and grade. Radical cystectomy has been the standard treatmentfor muscle-invasive local disease; however, combined-modality approacheswith the use of chemotherapy are gaining momentum withdata suggesting survival improvement. Patients with metastatic diseasehave poor long-term survival rates despite systemic multiagent chemotherapy.A variety of agents, including newer cytotoxic drugs and biologicallytargeted agents, are under investigation to determine the mosteffective regimen. The special needs of specific patient populations,such as the elderly, those with a suboptimal performance status, andpatients with medical comorbidities have gained more attention.Progress in the treatment of this disease is dependent on supportingongoing and future clinical trials.

In their historical review of the topicof malignant mesothelioma, Drs.Antman, Hassan, Eisner, and colleaguespoint out that the naturalhistory of malignant pleural mesotheliomahas not changed “over the past2 decades.” We disagree and suggestthat it was altered with the discoverythat the combination of pemetrexed(Alimta) and cisplatin is active in thissetting.[1] Subsequently, the largestphase III trial ever conducted in pleuralmesothelioma showed that mediansurvival improved by nearly4 months for pemetrexed/cisplatinrecipients, compared to treatment withcisplatin alone (13 vs 9 months,P < .001). Based on these data, theUS Food and Drug Administrationapproved pemetrexed, cisplatin, andsupplementation with vitamin B12 andfolic acid for the treatment of pleuralmesothelioma, and this regimen is nowthe standard of care.[2]

The field of palliative care hasgrown rapidly in recent yearsin response to patient need andclinician interest in effective approachesto managing chronic andlife-threatening illness. The article byKhatcheressian et al reviews the datathat make the case for palliative careas a core component of modern oncologypractice. They point out thatthe issue is not whether we have aquality problem here-it is clear thatwe do. Rather, the focus of this articleis on how best to address that problemin the context of the very real time andfinancial constraints in which we nowpractice oncology in the United States.

Drs. Henry, MacVicar, and Hussainprovide a timely reviewof the current management ofmuscle-invasive and metastaticurothelial cancer. The emerging roleof neoadjuvant chemotherapy and thepromise of novel, less toxic targetedtherapies are of particular interest inthe treatment of a disease in whichoutcomes remain poor for locally advancedand metastatic involvementdespite an aggressive multimodalityapproach.[1] We wish to briefly commenton three issues raised by theauthors: (1) the role of surgery in themanagement of invasive disease,(2) the indiscriminate use of neoadjuvantchemotherapy for clinically localizeddisease, and (3) the currentstatus of bladder-sparing approaches.

Optimal therapy for locally advancedbladder cancer aimsto prevent local recurrence,reduce the probability of distant metastasis,and improve survival. Radicalcystectomy coupled with a pelviclymph node dissection is the mainstaytreatment of locally invasive bladdercancer, curing the majority ofpatients with organ-confined bladdertumors, about half with extravesicaldisease, and a significant minoritywith lymph node metastases. Althoughradical cystectomy providesgood local and regional control of invasivebladder cancer, the recurrencefreeand overall survival rates are stillonly 63%–72% and 59%–66%, respectively,among all patients. Themajor predictors for disease-specificsurvival of patients following radicalcystectomy for bladder cancer are thepathologic stage of the primary tumorand status of lymph nodes at time ofcystectomy. Freedom from recurrenceat 5 years after cystectomy is 63%–72% for patients with organ-confineddisease and only 25%-37% for non-organ-confined disease.