(formato PDF). - Informazioni sui farmaci

Gianni Di Vagno
Unità Operativa di Ostetricia e Ginecologia, Casa Sollievo Della Sofferenza - San Giovanni
Rotondo
Sandro Pignata
UOC Oncologia Medica Dipartimento Uro-Ginecologico Istituto Nazionale Tumori, Fondazione G
Pascale - Napoli
Ovaio
Dalla revisione della letteratura degli ultimi 6 mesi poniamo in rilievo alcuni spunti di discussione
per quanto attiene al trattamento del carcinoma dell’ovaio.
Nel carcinoma dell’ovaio la chemioterapia di prima linea è rappresentata dalla combinazione di
carboplatino e taxolo. Nessuna altra combinazione a base di platino si è dimostrata superiore e, lo
schema rappresenta il braccio di controllo in tutti i trials in corso nel carcinoma dell’ovaio. Il gruppo
di ricerca JGOG ha recentemente pubblicato su Lancet (Abs n.1) i risultati di un interessante
studio di fase III che ha confrontato carboplatino/taxolo con schedula standard ogni 3 settimane
con un braccio sperimentale con carboplatino ogni 3 settimane e taxolo settimanale, “dose dense”,
alla dose di 80 mg/mq/settimana per 18 settimane consecutive. Lo studio ha randomizzato 637
pazienti ed i risultati mostrano un significativo vantaggio in termini di PFS (28 mesi vs 17.2) ed
overall servival a 3 anni (72.1% vs 65.1%) a favore dello schema contenente taxolo settimanale.
Tali dati, pur molto significativi, non consentono un cambio dello standard di trattamento; si ritiene
infatti che a causa delle differenze genetiche di popolazione tra pazienti giapponesi ed occidentali
sia necessario uno studio confirmatorio. In Italia attualmente è in corso lo studio MITO 7 che
intende rispondere allo stesso quesito, sebbene con alcune differenze sperimentali. Infatti, il
braccio sperimentale del MITO7 prevede la somministrazione settimanale di entrambi i farmaci,
con carboplatino AUC 2 e taxolo 60 mg/mq.
Una modalità alternativa per l’inserimento del taxolo settimanale nel trattamento di I linea è stata
esplorata dal gruppo tedesco NOGGO. In uno studio di fase II le pazienti ricevevano quattro cicli di
carboplatino, seguiti da 12 settimane di taxolo settimanale alla dose di 80 mg/mq (Abs n. 2) . La
somministrazione sequenziale dei due farmaci, con il taxolo dato settimanalmente, consente di
ridurre in modo drastico la tossicità del trattamento, con in particolare, la scomparsa di
neurotossicità significativa. In questo studio è stata osservata una PFS di 25.4 mesi che appare
molto interessante rispetto ai dati della letteratura.
La maggiore attesa per quanto attiene al trattamento medico del carcinoma dell’ovaio viene dagli
studi che cercano di incorporare i nuovi agenti biologici nel trattamento medico. Bevacizumab,
anticorpo anti-VEGF, è il farmaco più avanti come sviluppo. Due studi randomizzati di fase III sono
stati completati, il trial GOG 182 e l’ICON7, e nel 2010-2011 sono attesi i primi risultati. In entrambi
gli studi si è espolorata l’efficacia di bevacizumab sia in combinazione con carboplatino e taxolo
che come mantenimento. Di recente sono stati pubblicati sul Journal of Clinical Oncology i risultati
di uno studio di fase II con carboplatino, taxolo e bevacizumab, con quest’ultimo farmaco
somministrato concomitante alla chemioterapia ed anche successivamente come mantenimento
(Abs n.3). Si sono osservate risposte cliniche nel 75% dei casi e il 58% delle pazienti era libera da
progressione a 36 mesi. Un dato interessante è la presenza di 2 perforazioni intestinali su 62
pazienti trattate. La perforazione intestinale è stata segnalata con incidenza elevata soprattutto
negli studi in cui bevacizumab veniva impiegato nel carcinoma ovarico nel trattamento delle
recidive, cioè in pazienti pretrattate. L’incidenza secondo lo studio di fase II qui discusso, è minore,
sebbene anche l’impiego in prima linea debba essere accompagnato da una doverosa attenzione.
Nel trattamento della recidiva resta sempre aperto il quesito del ruolo della chirurgia citoriduttiva
secondaria (Abs n. 4). Una ricerca multicentrica italiana, pubblicata di recente su Gynecol Oncol,
suggerisce che le pazienti con recidiva linfonodale isolata possono beneficiare della citoriduzione
secondaria associata alla chemioterapia sistemica. In 69 pazienti osservate, ed analizzate in
analisi multivariate, lo studio suggerisce che la citoriduzione asscociata alla chemioterapia offre un
significativo vantaggio in termini di sopravvivenza rispetto alla sola chemioterapia. Il ruolo della
chirurgia della recidiva verrà probabilmente chiarito dallo studio DESKTOP III, condotto dal gruppo
tedesco AGO che randomizza le pazienti con score DESKTOP positivo (citoridotte alla prima
chirurgia, PS < 1, assenza di ascite) a ricevere o meno l’intervento chirurgico. Si tratta di uno
studio internazionale che vedrà anche la collaborazione di diversi centri italiani.
Cervice
Anche per la cervice ci sono state delle rilevanti pubblicazioni che possono avere un impatto sulla
pratica clinica. Sono stati pubblicati sul Journal of Clinical Oncology i dati dello studio randomizzato
GOG che ha confrontato quattro schemi di chemioterapia a base di cisplatino in associazione con
taxolo, vinorelbina, gemcitabina e topotecan (Abs n. 5) nel carcinoma della cervice metastatico.
Sono state randomizzate 513 pazienti e lo studio è stato chiuso dopo che una analisi ad interim ha
mostrato che nessuna delle schedule risultava superiore a cisplatino e taxolo (braccio standard
nello studio) in termini di sopravvivenza. I quattro schemi presentano in realtà pari efficacia,
purtroppo scarsa, e differente profilo di tossicità. La ricerca di trattamenti innovativi nel carcinoma
della cervice risulta una priorità, dati gli insoddisfacenti risultati della chemioterapia, Studi sono in
atto con bevacizumab, pazopanib e cetuximab, sebbene i risultati non siano attesi a breve.
Endometrio
E’ sicuro ed efficace l’approccio laparoscopico nel cancro endometriale? Gli autori italiani,
avvalendosi di una metanalisi basata su quattro trials controllati randomizzati, che confrontano il
tradizionale approccio laparotomico a quello laparoscopico concludono che, nei cancri endometriali
a stadio iniziale, è sicuro ed efficace il trattamento chirurgico mediante laparoscopia. Nonostante il
maggiore tempo operatorio la laparoscopia risulta gravata infatti da una minore perdita ematica
intraoperatoria e da un minore numero di complicanze postoperatorie. Questo messaggio
assolutamente condivisibile, a nostro giudizio, non può essere disgiunto da un concetto importante
e preliminare: non importa quali delle due tecniche chirurgiche vengano utilizzate ma è
assolutamente rilevante che tali tecniche siano utilizzate nell’ambito di una profonda cultura
oncologica, in un centro di riferimento oncologico che cumuli un numero minimo sufficiente di casi
per anno. Ricordiamoci che in altri paesi europei, come la Gran Bretagna è assolutamente
obbligatorio riferire ai centri oncologici riconosciuti, le patologie oncologiche prediagnosticate di
elezione, pena il mancato riconoscimento economico da parte del Sistema Sanitario Nazionale.
Questa centralizzazione dei casi sarebbe auspicabile anche nel nostro paese al fine di ottimizzare i
risultati ed i costi delle procedure chirurgiche (Abs n. 6). Ci sono dimostrate evidenze di beneficio
della linfoadenectomia pelvica in termini di tempo di sopravvivenza o di tempo libero di malattia nei
casi di carcinomi endometriali a stadio iniziale? La conclusione di questo studio multicentrico,
basato su 1408 pazienti, provenienti da 85 centri, è che non esistono evidenze di guadagno in
sopravvivenza e tempo libero da malatia dopo esecuzione della linfoadenectomia pelvica, e che,
quindi, al momento, tale procedura non sembra essere raccomandata come procedura routinaria
se non all’interno di trials clinici. A nostro parere, nella valutazione di quale strategia chirurgica
intraprendere, pesano numerose variabili di cui alcune classicamente intraistituzionali quali la
percentuale di accuratezza pre e post operatoria del grading e della invasione miometriale, ed il
tasso di complicanze da linfoadenectomia pelvica. A tale proposito è utile ricordare che la
disconcordanza del G pre e post chirurgico in letteratura varia dal 7% sino al 20% e quello dell’M,
valutato mediante RMN, è del 24% circa rispetto all’esame patologico definitivo, infine , per quanto
riguarda le complicanze da linfoadenectomia pelvica la media riportata in letteratura risulta intorno
al 17-19%, con ampie oscillazioni per centro. In questa zona di incertezza decisionale sarebbe
utile, anche per motivi medico-legali disporre, di statistiche “istituzionali” e coinvolgere negli incontri
multidisciplinari i patologi ed i radiologi enfatizzando l’importanza di controlli di qualità relativi alle
loro specifiche procedure diagnostiche (Abs n. 7)
Cervice
Quale approccio terapeutico è preferibile, ai fini di una migliore qualità di vita, tra chirurgia e
radioterapia nelle pazienti affette da cervicocarcinoma stadio IB e stadio IIA? A questa domanda
cerca di rispondere questo studio cinese basato sulle risposte ottenute dalla compilazione del
questionario EORTC per la valutazione della qualità di vita da parte di 202 pazienti dopo almeno 2
anni dalla fine del trattamento. I profili di effetti collaterali e tossicità acuti e duraturi sono molto
diversi tra i due trattamenti e ciò, a nostro avviso, richiede la sottoscrizione di un approfondito
consenso informato partecipato da parte delle pazienti, laddove devono essere particolarmente
enfatizzati, nel colloquio di orientamento al trattamento, l’importanza di alcuni fattori quali l’età,
l’aspettativa di vita e le comorbilità individuali preesistenti. Anche questa scelta dovrebbe essere
supportata da dati istituzionali di morbilità indotta con i due approcci terapeutici.(Abs n. 8)
Varie
Gli incontri multidisciplinary sulla discussione di casi clinici sono utili o sono solo una inutile perdita
di tempo per i medici specialisti? Questo quesito che assilla tutti noi nella pratica ospedaliera
quotidiana trova una brillante risposta e pesatura nell’originale lavoro di colleghi della Nuova
Zelanda. Gli AA hanno preso in considerazione un ototale di 509 casi discussi durante il periodo di
un anno solare. In questo periodo tali incontri multidisciplinari sono stati in grado di modificare
l’approccio terapeutico delle pazienti nel 6 % circa dei casi prevalentemente aggiungendo un
trattamento chemioterapico e/o chirurgico. Una percentuale bassa? Non proprio considerando che
tale documento, cofirmato da più specialisti, ha un importante ed indubbio valore medico-legale.
Quanto tempo avrebbe richiesto, per i colleghi della Nuova Zelanda, occuparsi di circa 30
contenziosi medico-legali per anno? (Abs n. 9)
Bibliografia
1. Katsumata N, Yasuda M, Takahashi F. et al. Dose-dense paclitaxel once a week in combination with
carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised
controlled trial. Lancet. 2009 Oct 17;374(9698):1303-5.
BACKGROUND: Paclitaxel and carboplatin given every 3 weeks is standard treatment for advanced
ovarian carcinoma. Attempts to improve patient survival by including other drugs have yielded
disappointing results. We compared a conventional regimen of paclitaxel and carboplatin with a
dose-dense weekly regimen in women with advanced ovarian cancer. METHODS: Patients with
stage II to IV epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer were
eligible for enrolment in this phase 3, open-label, randomised controlled trial at 85 centres in Japan.
Patients were randomly assigned by computer-generated randomisation sequence to receive six
cycles of either paclitaxel (180 mg/m(2); 3-h intravenous infusion) plus carboplatin (area under the
curve [AUC] 6 mg/mL per min), given on day 1 of a 21-day cycle (conventional regimen; n=320), or
dose-dense paclitaxel (80 mg/m(2); 1-h intravenous infusion) given on days 1, 8, and 15 plus
carboplatin given on day 1 of a 21-day cycle (dose-dense regimen; n=317). The primary endpoint
was progression-free survival. Analysis was by intention to treat (ITT). This trial is registered with
ClinicalTrials.gov, number NCT00226915. FINDINGS: 631 of the 637 enrolled patients were eligible
for treatment and were included in the ITT population (dose-dense regimen, n=312; conventional
regimen, n=319). Median progression-free survival was longer in the dose-dense treatment group
(28.0 months, 95% CI 22.3-35.4) than in the conventional treatment group (17.2 months, 15.7-21.1;
hazard ratio [HR] 0.71; 95% CI 0.58-0.88; p=0.0015). Overall survival at 3 years was higher in the
dose-dense regimen group (72.1%) than in the conventional treatment group (65.1%; HR 0.75, 0.570.98; p=0.03). 165 patients assigned to the dose-dense regimen and 117 assigned to the
conventional regimen discontinued treatment early. Reasons for participant dropout were balanced
between the groups, apart from withdrawal because of toxicity, which was higher in the dose-dense
regimen group than in the conventional regimen group (n=113 vs n=69). The most common adverse
event was neutropenia (dose-dense regimen, 286 [92%] of 312; conventional regimen, 276 [88%] of
314). The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group (214
[69%]) than in the conventional treatment group (137 [44%]; p<0.0001). The frequencies of other
toxic effects were similar between groups. INTERPRETATION: Dose-dense weekly paclitaxel plus
carboplatin improved survival compared with the conventional regimen and represents a new
treatment option in women with advanced epithelial ovarian cancer. FUNDING: Bristol-Myers
Squibb.
2. Oskay-Özcelik G, Chekerov R, Sommer H. et al. Sequential chemotherapy with carboplatin followed
by weekly paclitaxel in advanced ovarian cancer: Results of a multicenter phase II study of the
northeastern German society of gynecological oncology. Gynecol Oncol. 2009 Dec 1. [Epub ahead
of print]
BACKGROUND: For the adjuvant setting of advanced ovarian cancer (AOC) after primary radical
surgery the combination of paclitaxel and platinum in a 3-week schedule has emerged as the current
standard. In preclinical studies additional anti-angiogenic effects of low dose paclitaxel infusion were
demonstrated. A sequential schedule of carboplatin and paclitaxel has the potential to improve the
therapeutic index. METHODS: In this multicenter phase II trial four cycles of carboplatin at a dose of
AUC 5 (d1/q21d) followed by 12 cycles of weekly paclitaxel at a dose of 80 mg/m(2) (d1/q7d) were
applied after primary radical surgery. Eligible were all optimally or sub-optimally debulked patients
with FIGO IA-IV ovarian cancer. All patients with hemoglobin levels <12 mg/dl received
erythropoietin additionally. RESULTS: Between July 2003 and May 2005, 105 patients from 27
institutions were enrolled. The median age was 60 years (range: 23-80 years). A median number of
16 courses (range 1-16) were applied. The incidence of non-hematological toxicities was very low.
Only 41% of patients experienced alopecia (grade 1-2). Neurotoxicity (grade 3-4) was not observed.
Grade 3-4 hematological toxicity (43% of all patients) included thrombocytopenia (17%), anemia
(3%), leucopenia (23%), and neutropenic fever (0%). Ninety-seven percent received erythropoietin.
Thromboembolic events (4%) were not increased in patients who received erythropoietin. After a
median time of 23 months (range: 1-42 months) 32 patients had died, and the median overall
survival was not reached. The progression-free survival was 25.4 months (95% CI: 18.8-40+).
CONCLUSION: These results suggest that this sequential regimen using weekly paclitaxel
represents an efficacious and well-tolerated regimen. A randomized study comparing this new
schedule with the conventional 3-week protocol is warranted
3. Penson RT, Dizon DS, Cannistra SA et al. Phase II Study of Carboplatin, Paclitaxel, and
Bevacizumab With Maintenance Bevacizumab As First-Line Chemotherapy for Advanced Mullerian
Tumors. J Clin Oncol. 2009 Nov 16. [Epub ahead of print]
PURPOSE: New strategies are needed to improve outcomes for patients with advanced ovarian
cancer. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes vascular
endothelial growth factor but is associated with GI perforations (GIPs) in patients with recurrent
disease. PATIENTS AND METHODS: An open-label, phase II clinical trial was conducted in newly
diagnosed patients with stage >/= IC epithelial müllerian tumors. Patients received intravenous (IV)
carboplatin (area under the curve = 5), paclitaxel (175 mg/m(2) IV), and bevacizumab (15 mg/kg IV)
for six to eight cycles on day 1 every 21 days. Bevacizumab was omitted in the first cycle and
continued as a single agent for 1 year. RESULTS: Sixty-two women participated in this study. Fiftyone patients (82%) were optimally surgically cytoreduced before treatment. The median age was 58
years (range, 18 to 77 years). Forty-five women (73%) had ovarian cancer, 10 (16%) had peritoneal
cancer, four (6%) had fallopian tube cancers, and three (5%) had uterine papillary serous tumors.
The majority of patients (90%) had stage III or IV disease. A median of 17 maintenance cycles
(range, 0 to 25+ cycles) of bevacizumab (556 cycles) were administered with mild toxicity. Treatment
was associated with two pulmonary embolisms and two GIPs, all occurring during the chemotherapy
phase of treatment (364 total cycles). No grade 4 toxicities were seen during maintenance
bevacizumab treatment. Radiographic responses were documented in 21 (75%) of 28 women with
measurable disease (11 complete responses and 10 partial responses), with CA-125 responses in
76% of patients (11 complete responses, 21%; and 35 partial responses, 55%). The progressionfree survival rate at 36 months was 58%. CONCLUSION: The regimen of carboplatin, paclitaxel, and
bevacizumab with maintenance bevacizumab is feasible, safe, and worthy of future study in
advanced ovarian cancer
4. Gadducci A, Cosio S, Zola P. et al. The clinical outcome of epithelial ovarian cancer patients with
apparently isolated lymph node recurrence: A multicenter retrospective Italian study. Gynecol Oncol.
2009 Nov 30. [Epub ahead of print]
OBJECTIVES: To assess the clinical outcome of epithelial ovarian cancer patients who developed
an apparently isolated lymph node recurrence after primary therapy. METHODS: The authors
retrospectively assessed 69 patients with epithelial ovarian cancer who were clinically or
pathologically free of disease after primary therapy and who subsequently developed an apparently
isolated lymph node recurrence. The median follow-up of survivors was 74.5 months. RESULTS:
Median age was 58 years, FIGO stage was III-IV in 52 (75%) patients, residual disease after primary
surgery was >1 cm in 36 (52%), first-line chemotherapy consisted of paclitaxel-/platinum-based
chemotherapy in 44 (64%), time to recurrence was >12 months in 43 (62%), recurrence was pelvic
and/or para-aortic in 41 (59%), and treatment at recurrence consisted of chemotherapy alone in 44
(64%), surgery plus chemotherapy in 22 (32%), surgery alone in one patient, surgery plus irradiation
in one, and irradiation alone in one patient. Survival after recurrence was significantly related to the
type of treatment (chemotherapy alone versus surgery plus chemotherapy, median: 20.8 months
versus not reached, p=0.0002), and patient age (>58 versus <58 years, median: 26.8 versus 44.0
months, p=0.02). Overall survival was significantly related to the type of treatment (chemotherapy
alone versus surgery plus chemotherapy, median: 45.4 months versus not reached, p=0.0001),
patient age (>58 versus <58 years, median: 45.4 versus 62.9 months, p=0.03) and time to
recurrence (<12 months versus >12 months, median: 45.4 versus 66.9 months, p=0.01). Cox model
showed that treatment at recurrence was the strongest independent prognostic variable for both
survival after recurrence (hazard ratio [HR]=0.277, p=0.0003) and overall survival (HR=0.249,
p=0.0002). CONCLUSION: Patients who underwent surgery plus chemotherapy had a 72%
reduction in the risk of death after recurrence and a 75% reduction in the risk of death after initial
diagnosis when compared with those treated with chemotherapy alone. Secondary cytoreductive
surgery appears to be able to prolong survival in epithelial ovarian cancer patients with apparently
isolated lymph node recurrence.
5. Monk BJ, Sill MW, McMeekin DS et al. Phase III trial of four cisplatin-containing doublet
combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology
Group study. Journal of Clinical Oncology, Vol 27, No 28 (October 1), 2009: 4649-4655
PURPOSE: Assess toxicity and efficacy of cisplatin (Cis) doublet combinations in advanced and
recurrent cervical carcinoma. PATIENTS AND METHODS: Patients were randomly assigned to
paclitaxel 135 mg/m(2) over 24 hours plus Cis 50 mg/m(2) day 2 every 3 weeks (PC, reference arm);
vinorelbine 30 mg/m(2) days 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (VC); gemcitabine
1,000 mg/m(2) day 1 and 8 plus Cis 50 mg/m(2) day 1 every 3 weeks (GC); or topotecan 0.75
mg/m(2) days 1, 2, and 3 plus Cis 50 mg/m(2) day 1 every 3 weeks (TC). Survival was the primary
end point with a 33% improvement relative to PC considered important (85% power, alpha = 5%).
Quality-of-life data were prospectively collected. RESULTS: A total of 513 patients were enrolled
when a planned interim analysis recommended early closure for futility. The experimental-to-PC
hazard ratios of death were 1.15 (95% CI, 0.79 to 1.67) for VC, 1.32 (95% CI, 0.91 to 1.92) for GC,
and 1.26 (95% CI, 0.86 to 1.82) for TC. The hazard ratios for progression-free survival (PFS) were
1.36 (95% CI, 0.97 to 1.90) for VC, 1.39 (95% CI, 0.99 to 1.96) for GC, and 1.27 (95% CI, 0.90 to
1.78) for TC. Response rates (RRs) for PC, VC, GC, and TC were 29.1%, 25.9%, 22.3%, and
23.4%, respectively. The arms were comparable with respect to toxicity except for leucopenia,
neutropenia, infection, and alopecia. CONCLUSION: VC, GC, and TC are not superior to PC in
terms of overall survival (OS). However, the trend in RR, PFS, and OS favors PC. Differences in
chemotherapy scheduling, pre-existing morbidity, and toxicity are important in individualizing
therapy.
6. Palomba S; Falbo A; Mocciaro R et al. Laparoscopic treatment for endometrial cancer: a metaanalysis of randomized controlled trials (RCTs). Gynecol Oncol. 2009 Feb;112(2):415-21. Epub 2008
Oct 29.
OBJECTIVE: To define, if any, type I clinical evidence regarding the safety and efficacy of the
laparoscopic approach to endometrial cancer. METHODS: Meta-analysis of randomized controlled
trials (RCTs). RESULTS: Four RCTs were identified and included in the final analysis. No significant
difference between laparoscopic and laparotomic approaches to endometrial cancer in overall [odds
ratio (OR)=0.80, 95%CI 0.37 to 1.70, P=0.695], disease-free (OR=0.76, 95%CI 0.34 to 1.72,
P=0.655), and cancer-related (OR=0.89, 95%CI 0.19 to 4.13, P=0.815) survival was observed.
Significantly longer operative time (OR=53.48, 95%CI 37.28 to 69.68, P=0.0002), lower
intraoperative blood loss (OR=-266.86, 95%CI -454.82 to -78.90, P=0.005) and postoperative
complications (OR=0.40, 95%CI 0.23 to 0.70, P=0.007) were associated to laparoscopy. No effect of
laparoscopy on pelvic (OR=0.62, 95%CI -1.47 to 2.71, P=0.560) and para-aortic (OR=1.49, 95%CI 2.49 to 5.60, P=0.477) nodes yield, and intraoperative complications (OR=1.60, 95%CI 0.49 to 5.22,
P=0.390) was observed. CONCLUSIONS: Even if limited by few RCTs with short-term follow-up, our
data suggest that laparoscopic approach should be considered an effective and safe procedure for
patients with early stage endometrial cancer as well as laparotomic one. Notwithstanding the longer
operative time, advantages of the laparoscopy over traditional laparotomy regard intraoperative
blood loss and postoperative complications.
7. Kitchener H; Swart AM; Qian Q. et al. Efficacy of systematic pelvic lymphadenectomy in endometrial
cancer (MRC ASTEC trial): a randomised study. Lancet. 2009 Jan 10;373(9658):125-36. Epub 2008
Dec 16.
BACKGROUND: Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery
for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish
whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials
need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic
lymphadenectomy could improve survival of women with endometrial cancer. METHODS: From 85
centres in four countries, 1408 women with histologically proven endometrial carcinoma thought
preoperatively to be confined to the corpus were randomly allocated by a minimisation method to
standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes;
n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was
overall survival. To control for postsurgical treatment, women with early-stage disease at
intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the
ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number
ISRCTN 16571884. FINDINGS: After a median follow-up of 37 months (IQR 24-58), 191 women (88
standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16
(95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall
survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery
group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard
surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment
for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45;
p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14). INTERPRETATION: Our
results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic
lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be
recommended as routine procedure for therapeutic purposes outside of clinical trials.
8. Hsu WC; Chung NN; Chen YC et al. Comparison of surgery or radiotherapy on complications and
quality of life in patients with the stage IB and IIA uterine cervical cancer. Gynecol Oncol. 2009
Oct;115(1):41-5. Epub 2009 Jul 16.
OBJECTIVES: To compare the long-term complications and quality of life of patients with stage IB
and stage IIA uterine cervical carcinoma treated by surgery or radiotherapy. METHODS: From
August 2003 to May 2004, 202 patients with uterine cervical carcinoma were treated with surgery or
radiotherapy at two institutions and were enrolled in this study upon follow-up at least 2 years post
treatment. All patients completed the European Organization for Research and Treatment of Cancer
Quality of Life Questionnaire and complications Questionnaire. RESULTS: Constipation (p<0.001),
flushing (p<0.001), dysuria (p<0.001), urinary incontinence (p<0.01), dysparia (p<0.05) and vaginal
dryness (p<0.05) were statistically higher in the surgery treated group, while diarrhea (p<0.001),
bloody stools (p<0.001) and abdominal pain (p<0.01) were higher in the radiotherapy group. Using
factor analysis and introducing personal conditioned variables, pelvic neural dysfunction was
significantly higher in surgery group and intestinal dysfunction was higher in radiotherapy group.
There was no difference in sexual dysfunction between these two modalities. Comparison of EORTC
QLQ-C30 showed that the majority of issues had minimal differences between these two treatment
modalities, except social functioning (p<0.05; higher in radiotherapy group), constipation (p<0.001;
higher in surgery group) and diarrhea (p<0.01; higher in radiotherapy group). CONCLUSIONS: In
early stage uterine cervical cancer patients, surgery or radiotherapy resulted in different
complications, whereas long-term quality of life showed few differences between these two different
modalities. These data were helpful for physicians in regards to the changes of patients, and
moreover, for rehabilitation and supportive care of the patients after treatment.
9. Cohen, Paul MBBCh, MA et al. The Multidisciplinary Tumor Conference in Gynecologic OncologyDoes It Alter Management?
Objective: To assess the role of the multidisciplinary tumor conference in patient management in a
tertiary gynecologic oncology service.Methods: Data were analyzed from the records of all patients
presented at the gynecologic oncology tumor conferences at Auckland City Hospital from August 1,
2005, to August 1, 2006. Patient information including referral source, cancer site, stage, whether
surgery had been performed before the tumor conference and if so where and by whom, and benign
versus malignant was extracted from the records. The radiological and pathological findings and
diagnosis for each patient both before and after each tumor conference were compared. A
discrepancy was defined as a change in tumor site, histological type, grade, or stage that resulted
from findings discussed at the conferences. Diagnostic discrepancies that resulted in a change in
patient management were classified as major discrepancies. Discrepancies that did not affect patient
management were classified as minor discrepancies.
Results: A total of 509 cases were discussed during the study period. Forty-six discrepancies (9%)
were noted, with 30 major (5.9%) and 16 minor (3.1%) discrepancies. The most common changes to
patient management that resulted from the tumor conferences were the addition of chemotherapy
and surgery.
Conclusions: This study demonstrates that gynecologic oncology tumor conferences alter the diagnosis in a
significant number of cases and therefore affect patient management
A&S Anno 2009 n.4