Systemische Therapie des Zervixkarzinoms

Bis Mitte der 70er Jahre spielte die Chemotherapie im gesamten Behandlungskonzept nur eine marginale Rolle. Auch heute sind Operation und Strahlentherapie unver?ndert die Eckpfeiler der Behandlung. Für den Einsatz der Chemotherapie gibt es prinzipiell folgende Indkationsbereiche: █*Neoadjuvante Chemotherapie des fortgeschrittenen Prim?rkarzinoms (FIGO-Stadium IIb, III und IV), entweder vor der vorgesehenen Operation oder Strahlentherapie █*Simultane Radio-Chemo-Therapie █*Postoperative adjuvante Chemotherapie █*Palliative Chemotherapie (Lokalrezidive, Fernmetastasen) W?hrend die palliative Chemotherapie als etabliert bezeichnet werden darf, stellen die 3 erstgenannten Indika- tionen keine Standardtherapieempfehlung dar und müssen als experimentell bezeichnet werden. Diese Einschr?nkung ist haupts?chlich auf das Fehlen verbindlicher Daten aus prospektiv randomisierten Studien zurückzuführen und mu? bei der Aufkl?rung der Patientin Berücksichtigung finden.     

Systemische Therapie des Zervixkarzinoms

Die klassischen Therapieformen des Zervixkarzinoms bestehen in der Operation und der Radiotherapie. Die Chemotherapie hatte bis vor wenigen Jahren nur eine marginale Bedeutung. Nachdem unter der Anwendung einiger Zytostatika beim rezidivierenden Zervixkarzinom gute Remissionsdaten beobachtet werden konnten, etablierte sich die Chemotherapie in der palliativen Situation und wurde zunehmend in der kurativen Situation auf ihre Wirksamkeit untersucht. Zudem h?uften sich Hinweise auf einen Synergismus zwischen Chemotherapie und Radiatio.     

Diagnostik und Therapie des Zervixkarzinoms

Background

Cervical cancer is the third most common genital cancer in women in Germany. The choice of treatment depends on tumor stage, risk factors and individual patient characteristics.

Diagnostics and classification

Cervical cancer is clinically classified according to the Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stage. For this a clinical examination is necessary with the use of a speculum, bimanual vaginal and rectal examination, a gynecological examination with removal of material for cytological diagnostics and human papillomavirus (HPV) testing as well as a targeted biopsy by colposcopy or conization. Additionally, special diagnostics include an obligatory gynecological ultrasound investigation and renal sonography and further imaging methods can be helpful in uncertain situations and high-grade tumor stages.

Therapy recommendations

Lymph node staging is carried out for all patients with tumor stage FIGO IA2 and higher. Up to tumor stages FIGO IB–IIB, radical hysterectomy combined with pelvic and if necessary para-aortic lymph node staging are performed. Chemoradiotherapy leads to similar results compared to open surgery regarding long-term survival but differs in the side-effect profile and recurrence pattern. Sentinel lymph node dissection is being tested in clinical trials. For patients suffering from locally advanced cancer FIGO stage III primary chemoradiotherapy is recommended and for patients with FIGO stage IV tumors individual treatment should be considered. Adjuvant chemoradiotherapy is conducted in high risk patients. In advanced FIGO stage IVb and recurrent cervical cancer primary chemotherapy represents the therapeutic option.

Conclusion

By adequate diagnostics and therapy decisions over-therapy and under-therapy can be avoided and the optimal treatment for each stage can be found. For the corresponding early tumor stage a fertility-retaining treatment is possible. In this way even comorbidities can be avoided as far as possible by a combination of therapeutic procedures.     

Diagnostik und Therapie des Zervixkarzinoms

best practice onkologie - Während sich in den Industrienationen die Inzidenz des Zervixkarzinoms seit Jahren rückläufig zeigt, ist die durch eine persistierende Infektion mit HPV...     

Therapie der fortgeschrittenen Stadien des invasiven Zervixkarzinoms

Die Therapie der fortgeschrittenen Stadien des Zervixkarzinoms war in den letzten Jahren von der z. T. kontroversen Diskussion über die Wirksamkeit der operativen Therapie gegenüber der Strahlentherapie gepr?gt. Beide Therapieoptionen galten bezüglich der Ergebnisse als ?quivalent.     

Aktuelle Studien zur Therapie des Zervixkarzinoms in den USA

Experimentelle therapeutische Ans?tze sind v. a. bei Zervixkarzinomen mit ungünstigen Prognosekriterien, fortgeschrittenem Stadium, prim?r refrakt?rer Erkrankung und im Rezidiv notwendig. In der vorliegenden Arbeit fassen wir die Studien zusammen, die zurzeit in den USA neue Modalit?ten zur Therapie des Zervixkarzinoms untersuchen (Tabelle 1). Chirurgische, chemotherapeutische und immunologische Behandlungsformen sowie Kombinationstherapien werden unterschieden.     

Operative Therapie des Endometriumkarzinoms

Surgery is the therapy of choice in the primary treatment of patients with endometrial cancer. With the rising incidence of obesity, the number of patients with endometrial cancer will also increase. However, operations in obese patients are more challenging. Laparotomy as standard therapy in patients with endometrial cancer stages I and II should be replaced by laparoscopic approaches. Laparoscopy is oncologically equivalent to open procedures and offers many advantages to patients, especially those with relevant comorbidities. Robotic surgery for endometrial cancer is still under evaluation. The most controversial point of treatment today is the indication for and extent of lymphadenectomy in different stages. In advanced tumor stages, optimal debulking should be performed to improve the effectiveness of adjuvant chemotherapy and/or radiation therapy.     

Operative Therapie des Endometriumkarzinoms

Zusammenfassung Das Endometriumkarzinom ist der häufigste bösartige Tumor des inneren Genitales. Bei früher Diagnose und konsequenter Therapie können Heilungsraten von über 80% erzielt werden. Hauptsymptom ist die irreguläre Monatsblutung oder die Blutung nach der Menopause, die immer abklärungsbedürftig ist. Die Diagnose ergibt sich nach Hysteroskopie und fraktionierter Abrasio. Im Mittelpunkt der Behandlung steht die Staging-Laparotomie per medianen Längsschnitt mit Entfernung der Gebärmutter und der Eierstöcke. Die operative Behandlung sollte von vornherein in einem onkologischen Zentrum erfolgen, wo diese Operation routinemäßig durchgeführt wird. Das leparoskopisch essistierte Vorgehen ist eine Alternative zur Standardoperation. Die Therapie wird je nach Stadium durch postoperative Bestrahlung ergänzt. Die Entfernung der pelvinen und ggf. der paraaortalen Lymphknoten sollte bis auf die Stadien mit einer sehr günstigen Prognose (Ia, b und G1 bei endometroider Histologie) bei allen Patientinnen durchgeführt werden. Eine systemische adjuvante Therapie (Hormon- und/oder Chemotherapie) bringt keine Vorteile.     

Operative Therapie des malignen Melanoms

The right operative therapy plays a key role in the management of malignant melanoma. If the diagnosis of melanoma is likely, an excision biopsy of the entire pigmented lesion is strongly recommended. After the diagnosis has been confirmed by histology, a safety margin should be excised in accordance with the tumor thickness (a 1-cm safety margin in tumors up to 2 mm in thickness and 2 cm in tumors thicker than 2 mm). In melanoma of the face or genital region, the safety margins can be reduced if the tumors are excised under micrographic control. In patients with a vertical tumor thickness of 1 mm or more, it is recommended to obtain a sentinel lymph node biopsy (SLNB). In the case of unfavorable prognostic factors such as ulceration or regression of the primary tumor or Clark level IV or V, a SLNB is recommended even in primary tumors of less than 1 mm thickness. A radical regional lymphadenectomy is recommended in cases of lymph node metastases. Distant metastases involving only one organ should be excised if possible. If the patient has multiple skin metastases (in-transit or satellite metastases) in only one extremity, isolated limb perfusion (melphalan with or without TNF-α) is an effective treatment combining surgical and oncologic strategies.     

Operative Therapie des lokal begrenzten Prostatakarzinoms

Background

Radical prostatectomy is the most frequently used therapy for localized prostate cancer. Staging measures are based on the preoperative parameters prostate-specific antigene (PSA) level, the Gleason score of biopsy material and the results of the digital rectal examination for diagnostics of the extent of tumor spread. For low risk cancers (PSA <?10 ng/ml, cT1c–cT2a and Gleason sum ≤?6) no further imaging diagnostics should be performed.

Results

Radical prostatectomy can be performed by open surgery (ORP), laparoscopically (LRP) or robot-assisted (RALP). In a prospective randomized trial radical prostatectomy significantly reduced local progression, distant metastases and prostate cancer mortality compared to watchful waiting. Progression-free survival after radical prostatectomy is >?80?% after 7 years and cancer-specific survival rates of >?90?% after 15 years have been reported. Perioperative complications are observed in 9?% of the patients. In recent retrospective studies incontinence rates between 8 and 11?% were reported. Depending on tumor stage a nerve sparing approach is possible and results in postoperative potency rates between 50 and 90?%.

Conclusions

Surgeons experience is of paramount importance for the outcome of radical prostatectomy. Furthermore, comparisons of retrospective data suggest that RALP improves a number of short-term outcomes. Two randomized studies showed concordantly significantly better continence and potency rates after RALP compared to conventional LRP.     

Operative Therapie des Vulva- und Vaginalkarzinoms

Context

Whereas decades ago, vulvar cancer was a tumor primarily diagnosed in elderly women, nowadays, this tumor is increasingly diagnosed. The rising incidence is mainly due to the increasing number of young women presenting with these tumors.

Methoden

Research of the literature and analysis of own results.

Results

Depending on the age of the women persistent infection with high risk human papillomavirus is responsible for the development of these lesions, in the young age group in about 30–50?% of the cases. More than 50?% (own data) of the tumors are located between the clitoris and urethra. Standard treatment is tumor resection with sufficient margin or (partial) vulvectomy and complete inguinofemoral lymphadenectomy or sentinel node biopsy in specialized centers. New therapy options are reconstruction of the vulva with local skin flaps to improve esthetic and functional outcome especially in young, sexually active women.     

Operative Therapie des lokal begrenzten Prostatakarzinoms

Prostate cancer is the most common cancer in men in Germany with increasing tendency, particularly of the potentially curable locally limited stages. The most commonly carried out operative procedures in Germany are the open radical retropubic prostatectomy (ORP) and robot-assisted laparoscopic radical prostatectomy (RARP), with and without lymphadenectomy. In comparative retrospective studies both procedures show no differences with respect to the oncological results. Differences in functional results have been reported but are controversial. The aims of operative therapy are retention of urine continence and penile tumescence in addition to complete removal of the prostate gland. An improvement of the functional results can be achieved by retention of the intrafascial nerve, intraoperative rapid frozen section technique or retention of the maximum length of the external sphincter of the urethra.     

Operative Therapie des nichtinvasiven und invasiven Mammakarzinoms

Breast-conserving surgery has become the standard procedure for local treatment of breast cancer today. Preinvasive and other nonpalpable lesions require an interdisciplinary approach with wire-guided localisation. If a larger resection is necessary, oncoplastic surgical techniques are helpful to prevent unsatisfactory cosmetic results. Primary chemotherapy has further increased the conservative options in locally advanced tumours. A variety of different reconstructive methods, including both prosthetic reconstruction and autologous flap reconstruction, can be offered to those patients who require mastectomy. Sentinel node biopsy can be done in almost half the cases of primary breast cancer. Because of the advanced surgical techniques used today, morbidity after breast surgery has been reduced, and an ongoing gain in quality of life for breast cancer patients has been achieved.     

Diagnostik des Zervixkarzinoms

Background

Cervical cancer can be subdivided into stages I–IV according to the Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) classification. According to the literature local clinical staging shows an error rate of 17–32?% in patients with early stage (FIGO 1B) cervical cancer and up to 65?% in advanced stages of cervical cancer (FIGO III–IV) and consequently has a negative influence on the prognosis. According to the guidelines of the German Society of Gynecology and Obstetrics (DGGG), the working group on gynecological oncology (AGO) and the German Cancer Society (DKG) the use of modern cross-sectional imaging diagnostics, such as magnetic resonance imaging (MRI) and computed tomography (CT) for staging is recommended for the first time. The MRI investigation of the pelvis is recommended for pretherapeutic staging from stage IB2 onwards. Because of its high soft tissue contrast, MRI allows excellent non-invasive local staging of cervical cancer with direct demonstration of tumors as well as assessment of the prognosis based on morphological imaging features.

Results and Conclusions

The diagnostic accuracy of MRI in the preoperative assessment of tumor size and in the differentiation between operable and advanced non-operable stages of cervical cancer is 83–93?%; therefore, MRI is considered to be not only the optimal modality for diagnostic evaluation and staging of cervical cancer starting from FIGO stage IB2 but also for planning of radiation therapy and for exclusion of recurrence during follow-up. Several studies have recently evaluated the feasibility and value of MRI combined with positron emission tomography (PET) in oncological settings and have shown that improved diagnostics can be achieved by which optimal local and also nodal staging and follow-up control of therapy are possible.

Objective

This article gives an overview of the current diagnostic imaging modalities of uterine cervical cancer using CT, MRI and combined functional and molecular hybrid imaging with integrated PET-CT and PET-MRI for pretherapeutic local staging and for nodal staging.

     

Radioonkologische Aspekte des Zervixkarzinoms

Chemoradiotherapy is an integral component of cervical cancer treatment in cases where surgery alone is not sufficient to achieve an optimal oncological outcome. The present German interdisciplinary guidelines on treatment of cervical cancer recommend performing either radical hysterectomy or primary chemoradiotherapy. The frequently used practice of trimodal therapy (i.e. radical hysterectomy, radiation and chemotherapy) doubles the risk for treatment-related delayed toxicity and should be avoided whenever possible. If risk factors are known prior to therapy, e.?g. lymph node metastases, parametrial infiltration or a combination of tumor size >4 cm, grade 3, lymphovascular space invasion (LVSI) or deep stromal infiltration, primary chemoradiotherapy should be recommended. The purely clinical FIGO classification does not consider lymph node involvement. This leads to a high rate of adjuvant chemoradiotherapy after radical surgery due to lymph node involvement. This could have been avoided in 90?% of patients, if surgical (laparoscopic) lymph node staging would have been used routinely. Whether this can result in advantages for patients with respect to the prognosis, was one of the aims of the Uterus-11 study of the working group for gynecological oncology (AGO) and the working group on radiological oncology (ARO).Mature data are expected to be available in 2018. For chemoradiotherapy sophisticated irradiation techniques should be used, which are available in all German treatment facilities. This is the only way to reduce acute and delayed side effects. Although ovarian preservation by ovarian transposition and organ sparing can be provided to premenopausal patients, a pregnancy after full-dose chemoradiotherapy is unlikely because of the resulting atrophy of the endometrium and fibrosis of the myometrium. Oncological results depend on treatment quality, full-dose external beam radiation, the use of brachytherapy and the administration of concomittant chemotherapy. The experience of the treatment facility is a predictor for patient outcome. The value of neoadjuvant chemotherapy in locally advanced cervical cancer is unclear and still under discussion.