ONCOLOGY Vol 18 No 3

The myriad effects of androgendeprivation therapy (ADT) inmen were really not appreciateduntil those without metastatic prostatecancer received such treatment.For example, fatigue-now recognizedas a common toxicity of ADT-was once more likely attributed tometastatic disease. Today, however,patients who are otherwise fully functional,healthy, and asymptomatic arebeing treated for a rising prostate-specificantigen level after primary therapy.In these men, the side effects ofADT can be very dramatic and aremore clearly related to the initiationof therapy.

For the past 60 years, the treatmentof advanced prostate cancerhas consisted of deprivingcancer cells of androgens.[1] The keypremise of androgen ablation is thatmost prostate carcinoma cell growthis initially androgen-dependent. Theandrogen receptor expressed by thesecells binds dihydrotestosterone, whichis then transported into the nucleus,leading to a cascade of events thatinduce cellular growth. If androgen isremoved, cellular death ensues via apoptosisof the androgen-sensitive cells.

Lannin and Haffty provide aninteresting and informative reviewon the management andclinical course of an ipsilateral breasttumor recurrence (IBTR) followinglumpectomy and breast irradiation forprimary breast cancer. They presentan engaging discussion concerningthe distinction of a true recurrencefrom a new primary tumor within theipsilateral breast. Although bothevents are included in the term IBTR,the authors point out that the morefavorable outcome follows treatmentof a new primary as opposed to a truerecurrence. Presumably, the true recurrencewould indicate tumor thathas not been eradicated by surgeryand radiotherapy (with or without systemictherapy), which would be amore aggressive malignancy. Thebetter prognosis for a new primarynotwithstanding, there is still a lackof data to indicate whether treatmentshould be different for these twoentities.

Androgen deprivation, as a form of treatment for prostate cancer,has been used for decades. Within the last decade, however, its use hasincreased significantly. Therefore, it is incumbent upon the physicianto be familiar with the side effects associated with this treatment. Someof these side effects (eg, osteoporosis, changes in lipid profiles, andanemia) may be associated with significant morbidity, whereas others(eg, impotence, decreased libido, fatigue, and hot flashes) primarilyaffect the patient’s quality of life. Prevention strategies and treatmentsexist for many of these side effects. In addition, alternative forms ofantiandrogen therapy such as intermittent hormone ablation andantiandrogen monotherapy may be effective, with the added benefit ofminimizing side effects. This review focuses on the wide range of sideeffects associated with androgen ablation as well as preventive and treatmentstrategies.

Oncologists grapple with an element of psychological stress that relatesto the suffering their patients experience. Although this stress maynot be unique to oncology, it is profound. When these stresses becomeoverwhelming, they lead to physician burnout. It is important to understandwhat makes an oncologist feel successful, what coping strategieshelp combat burnout, and what adds to the process of renewal. Thedoctor-patient relationship plays an important role for many oncologistsin this regard, and communication skills are increasingly recognizedfor their importance in this arena. We outline several clinical scenariosthat pose particular challenges to oncologists. These include breakingbad news and the patient’s response to hearing bad news, transitions incare and offering end-of-life care, participation in investigational studies,error disclosure, complementary and alternative medicine, spirituality,family discussions, and cross-cultural issues. By highlighting therelevant psychosocial issues, we offer insight into, and tools for, anenriched dialogue between patient and oncologist. The doctor-patientrelationship can be viewed as the ultimate buffer for dealing with thehassles encountered in clinical oncology.

In this issue of ONCOLOGY, Sonodaprovides a systematic reviewof the management of early ovariancancer. The author rightfully concludesthat comprehensive surgicalstaging should be performed in thesepatients and that, based on severalEuropean randomized studies, patientswith high-risk early ovarian cancershould be treated with adjuvant platinum-based chemotherapy. Importantquestions remain, however, including:How should high-risk early ovariancancer be defined? and Is there a needfor adjuvant chemotherapy in patientswho have undergone comprehensivesurgical staging?

Dr. Sonoda has provided a thoroughsummary of the managementof early-stage ovariancancer. He highlights the importanceof accurate and completesurgical staging of this disease entity.Laparoscopic staging is discussed asa potential alternative to the classicopen laparotomy staging procedure.In addition, the author includes anextensive review of trials discussingchemotherapy, radiation therapy, andintraperitoneal therapy as adjuvanttreatment for early-stage disease.

In their article, Armstrong and Hollandbriefly review many of thereasons why the practice of oncologyis likely to be stressful, includingthe factors that lead to burnoutor feelings of being overwhelmed.The article then goes on to focus onways to enhance communication inthe clinical setting as an important

Androgen deprivation therapy(ADT) with a gonadotropinreleasinghormone agonist isthe cornerstone of treatment for metastaticprostate cancer. Patterns of carehave changed dramatically over thepast decade, and gonadotropin-releasinghormone agonists are now routinelyadministered to men withoutradiographic evidence of metastases.These agents account for about onethirdof Medicare expenditures for thetreatment of prostate cancer[1]; in1999, that portion exceeded $800 million.The routine use of gonadotropin-releasing hormone agonists in menwith nonmetastatic prostate cancer increasesthe importance of understandingand preventing treatment-relatedadverse effects. In this issue ofONCOLOGY, Dr. Holzbeierlein andcolleagues provide a timely summaryof the adverse effects of ADT.

Over the past 20 years, the combinationof breast-conservationsurgery and radiationtherapy has become the most commontreatment for the majority of patientswith invasive and in situ breastmalignancies. Extensive data fromboth randomized trials[1-3] and largeclinical databases have shown that thisapproach is equal to mastectomy interms of survival and provides excellentquality of life and patient acceptance.Nevertheless 10% to 15% ofpatients treated with breast-conservationsurgery and radiation will have alocal recurrence within the ipsilateralbreast (IBTR) within 10 years.[4-8]This paper will review the biology,clinical management, and outcomeof patients with ipsilateral breastrecurrence.

Armstrong and Holland’s articleprovides a clear and concisediscussion of many ofthe problems oncologists face in thehigh-pressure/high-stakes world of21st century medicine. Physicians ingeneral, and oncologists in particular,are overburdened with demandson their time, energy, and emotions.The authors present suggestions forrelieving these stresses in the formof a “survival kit.” The survival kit isinteresting because it provides an educationon how to communicate withpatients and deal with the emotionalaspects of practicing medicine.

Drs. Lannin and Haffty’s comprehensiveand thoughtful reviewof breast cancer recurrencefollowing breast-conservingtherapy details the risk factors forlocal recurrence, factors predictive ofoutcome at the time of a breast recurrence,and prognosis after recurrence.The complex interaction betweenlocal and distant recurrence is alsoexplored; the authors argue thatlocally recurrent disease is both amarker of a more aggressive primarycancer, as well as a potential sourcefor seeding distant sites. Strategiesfor managing local recurrences arealso discussed. We are in agreementwith this excellent review and willtake this opportunity to expand on afew points.

About 10% to 15% of patients who undergo breast-conservation surgeryand radiation therapy will subsequently develop ipsilateral breasttumor recurrence (IBTR). This paper reviews the biology, clinical management,and outcome of this entity. Risk factors for IBTR includeyoung age, positive microscopic margins, gross multifocality, an extensiveintraductal component, and lymphatic vessel invasion. The standardtherapy following IBTR has been mastectomy, but interest in furtherbreast-conservation approaches has recently arisen. Although theoutcome following salvage therapy is quite good, the risk of distantmetastases for patients with IBTR is three to five times greater than forthose without recurrence. The reason for this association has been controversial,but it now appears that IBTR is both a marker of the underlyingbiologic aggressiveness of the tumor and a source for furthertumor metastasis. Monitoring of patients following lumpectomy andradiation therapy, and aggressive therapy for IBTR when diagnosed,are clearly warranted. Prognostic factors at the time of IBTR and implicationsfor local and systemic therapy are discussed.

Epithelial ovarian cancer is the leading cause of death from gynecologicmalignancies in the United States due, in large part, to the advancedstage at which it is commonly diagnosed. However, approximatelyone-third of cases are discovered at an early stage, when tumoris limited to the pelvis. Certain prognostic factors have been identified,which place patients with early disease at risk for recurrence and warrantthe use of adjuvant therapy. Systemic chemotherapy remains themost commonly used adjuvant therapy in this setting, and several randomizedEuropean trials have recently suggested a benefit to its use.These studies, however, suffered from the lack of comprehensive staging,which must be considered when interpreting the literature on earlystagedisease. Ideally, these patients should have access to a gynecologiconcologist prior to their initial surgical procedure.