Cervical cancer is frequently diagnosed in women during their reproductive years, and fertility preservation is an essential part of their cancer treatment. In highly selected patients with early ...stage, low-risk cervical cancer and a tumor size ≤ 2 cm, several treatment strategies can be offered for patients wishing to preserve fertility, including radical/simple trachelectomy or conization with pelvic lymph node assessment. Trachelectomy can be performed through a vaginal, abdominal, or minimally invasive approach and has been shown to have an equivalent oncologic outcome compared to radical hysterectomy. All surgical approaches for radical trachelectomy seem to have excellent survival with comparable oncologic outcomes. Nevertheless, patients undergoing vaginal trachelectomy have better obstetric outcomes compared to the other routes. In patients with larger tumors (2-4 cm), neoadjuvant chemotherapy followed by fertility-sparing surgery is an alternative option. Several chemotherapy regimens have been used for this indication, with a pathologic complete response rate of 17-73%. For locally advanced diseases that require radical hysterectomy or primary chemoradiation, fertility preservation can be performed using oocyte, embryo, or ovarian tissue cryopreservation, as well as ovarian transposition. For these patients, future pregnancy is possible through surrogacy. In addition to fertility preservation, ovarian transposition, where the ovaries are repositioned outside of the radiation field, is performed to maintain ovarian hormonal function and prevent premature ovarian failure. In summary, fertility-preservation treatment strategies for patients with early stage cervical cancer are continuously evolving, and less radical surgeries are becoming more acceptable. Additional and ongoing evidence is helping determine the impact of conservative procedures on oncologic and obstetric outcomes in these patients.
Cer vical cancer is the fourth most common cancer in women 1. While we hope globalhuman papillomavirus vaccination efforts will change this reality, as a result of screeningprograms 42% of women in ...North America present with localized disease 2. Radicalhysterectomy has been recommended for most patients, presenting with stage IA2 to 4 cmIB3 cancers 3. Overall sur vival is excellent, however there are significant adverse effectsassociated with parametrial and vaginal resection 4.
We congratulate Plante et al. on completing this randomized non-inferiority trial of 700patients with stage 1A2 and 1B1 cer vical cancer comparing simple hysterectomy and pelvicnode dissection to radical hysterectomy and pelvic node dissection (recently published inthe New England Journal of Medicine) 5. The primar y endpoint was designed to detect non-inferiority of pelvic-relapse free sur vival at 3 years, with secondar y outcomes including overallsur vival, parametrial involvement, quality of life and treatment-related toxicity. The 3-yearpelvic-recurrence rate was 2.5% in the simple hysterectomy group and 2.2% in the radicalhysterectomy group per intention to treat analysis (2.8% and 2.3% per protocol analysis) andthe upper 95% confidence limit did not meet the pre-defined threshold of inferiority. The3-year extra pelvic relapse-free sur vival and overall sur vival were 98.1% vs. 99.7% and 99.1%vs. 99.4%, respectively. Surgical margins were similar (2.4% SH vs. 2.7% RH).
Patient reported outcomes of sexual health were measured by the Female Sexual FunctionIndex and the Female Sexual Distress Scale-Revised, and bowel, bladder and non-sexualvaginal symptoms were measured by EORTC QLQ-C30 with QLQ-CX24. Simple hysterectomywas associated with decreased pain experience and favorable sexual health. Patients whounder went simple hysterectomy reported less sexual worr ying and increased sexual enjoymentat 3 months, less sexual pain and improved sexual lubrication for the first 12 months, andimproved sexual vaginal functioning for the first 24 months. Overall better body image andincreased sexual activity was reported for up to 36 months. Decreased urinar y retentionand incontinence also favored simple hysterectomy (0.6% vs. 9.9% and 4.7% vs. 11%,respectively). These findings of decreased sexual health and increased bladder symptoms inpatients undergoing radical hysterectomy are consistent with the literature 6-9.
The ConCer v trial prospectively evaluated patients with cer vical cancer up to 2 cm, treatedwith conization or simple hysterectomy, and concluded conser vative surger y may be offeredbased on a cumulative recurrence of 3.5% over a median follow up of 36.3 months 10.A systematic review of the literature including 2,662 women demonstrated no significantassociation between mortality and simple vs. radical hysterectomy in patients withmicroscopic disease, and the recent SCCAN retrospective trial of 1,257 patients comparingtype B, C1 and C2 radical hysterectomy techniques found no sur vival difference for tumors upto 2 cm with increased radicality of surger y 11,12.
What can we conclude from all this? The evidence from these studies is congruent; nonradical surger y for small cer vical cancers is safe, not associated with increased relapse rates,and improves quality of life, measured through patient reported outcomes. Rarely do wefind a therapy, that relative to standard of care, is as effective yet less complex, less costly andbetter tolerated by patients. While it is unlikely this study will be replicated, these findingsstimulate additional questions. With no reason to suspect other wise, will the 5-year overallsur vival be consistent with these 3-year findings? Given that the majority of patients inthe ConCer v trial (96%) and the SHAPE trial (75%) under went minimally invasive surger yfor their hysterectomy, what is the optimal surgical approach for these patients 10,13?Can sentinel node biopsy replace full pelvic lymphad... KCI Citation Count: 0
Whether sentinel lymph node biopsy (SLNB) can replace lymphadenectomy for surgical staging in patients with high-grade endometrial cancer (EC) is unclear.
To examine the diagnostic accuracy of, ...performance characteristics of, and morbidity associated with SLNB using indocyanine green in patients with intermediate- and high-grade EC.
In this prospective, multicenter cohort study (Sentinel Lymph Node Biopsy vs Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging SENTOR study), accrual occurred from July 1, 2015, to June 30, 2019, with early stoppage because of prespecified accuracy criteria. The study included patients with clinical stage I grade 2 endometrioid or high-grade EC scheduled to undergo laparoscopic or robotic hysterectomy with an intent to complete staging at 3 designated cancer centers in Toronto, Ontario, Canada.
All patients underwent SLNB followed by lymphadenectomy as the reference standard. Patients with grade 2 endometrioid EC underwent pelvic lymphadenectomy (PLND) alone, and patients with high-grade EC underwent PLND and para-aortic lymphadenectomy (PALND).
The primary outcome was sensitivity of the SLNB algorithm. Secondary outcomes were additional measures of diagnostic accuracy, sentinel lymph node detection rates, and adverse events.
The study enrolled 156 patients (median age, 65.5 years; range, 40-86 years; median body mass index calculated as weight in kilograms divided by height in meters squared, 27.5; range, 17.6-49.3), including 126 with high-grade EC. All patients underwent SLNB and PLND, and 101 patients (80%) with high-grade EC also underwent PALND. Sentinel lymph node detection rates were 97.4% per patient (95% CI, 93.6%-99.3%), 87.5% per hemipelvis (95% CI, 83.3%-91.0%), and 77.6% bilaterally (95% CI, 70.2%-83.8%). Of 27 patients (17%) with nodal metastases, 26 patients were correctly identified by the SLNB algorithm, yielding a sensitivity of 96% (95% CI, 81%-100%), a false-negative rate of 4% (95% CI, 0%-19%), and a negative predictive value of 99% (95% CI, 96%-100%). Only 1 patient (0.6%) was misclassified by the SLNB algorithm. Seven of 27 patients with node-positive cancer (26%) were identified outside traditional PLND boundaries or required immunohistochemistry for diagnosis.
In this prospective cohort study, SLNB had acceptable diagnostic accuracy for patients with high-grade EC at increased risk of nodal metastases and improved the detection of node-positive cases compared with lymphadenectomy. The findings suggest that SLNB is a viable option for the surgical staging of EC.
Opinion statement
Most individuals with gestational trophoblastic neoplasia (GTN) are cured with chemotherapy; however, about 5% of them will develop chemotherapy-resistant disease and will die of ...disease progression. Most GTN tissues express programmed death ligand-1 (PDL-1), making immune checkpoint inhibitors (ICIs) targeting this pathway an attractive treatment option for individuals with GTN. There is increasing evidence to support the use of ICIs for individuals with recurrent or resistant GTN, but available data are derived from case reports and small single arm trials. As promising as it seems, not all individuals with GTN respond to ICIs, and there is lack of evidence toward which factors mediate the effect of ICIs on GTN. In addition, treatment-related adverse events and impact on future fertility are not negligible and should be considered before initiating this treatment. Therefore, additional research is needed to evaluate treatment outcome of ICIs in GTN compared to standard treatment, and to identify molecular and clinical predictors for treatment response, before this treatment is incorporated into the standard of care.
The aim of this study was to explore the outcomes of pelvic reconstruction with a rectus abdominis myocutaneous (RAM) or rectus abdominis myoperitoneal (RAMP) flap following radical surgery for ...gynecologic malignancy. This is a retrospective case series of all pelvic reconstructions with RAM or RAMP flap performed in a gynecologic oncology service between 1998 and 2023. Reconstructions with other flaps were excluded. A total of 28 patients were included. Most patients had vulvar cancer (
= 15, 53.6%) and the majority had disease recurrence (
= 20, 71.4%). Exenteration was the most common procedure, being carried out in 20 (71.4%) patients. Pelvic reconstruction was carried out with a RAM flap in 24 (85.7%) cases and a RAMP flap in 4 (14.3%) cases. Flap-specific complications included cellulitis (14.3%), partial breakdown (17.9%), and necrosis (17.9%). Donor site complications included surgical site infection and necrosis occurring in seven (25.0%) and three (10.7%) patients, respectively. Neovaginal reconstruction was performed in 14 patients. Out of those, two (14.3%) had neovaginal stenosis and three (21.4%) had rectovaginal fistula. In total, 50% of patients were disease-free at the time of the last follow up. In conclusion, pelvic reconstruction with RAM/RAMP flaps, at the time of radical surgery for gynecologic cancer, is an uncommon procedure. In our case series, we had a significant complication rate with the most common being infection and necrosis. The development of a team approach, with input from services including Gynecologic Oncology and Plastic Surgery should be developed to decrease post-operative complications and improve patient outcomes.
There is no consensus on the best regimen for the primary treatment of low-risk gestational trophoblastic neoplasia (GTN).
Two commonly used single-drug regimens were compared with respect to the ...proportion of patients meeting the criteria for a complete response (CR) in a randomized phase III trial conducted by the Gynecologic Oncology Group. Eligibility was purposefully broad to maximize the generalizability of the results and included patients with a WHO risk score of 0 to 6 and patients with metastatic disease (limited to lung lesions < 2 cm, adnexa, or vagina) or choriocarcinoma.
Two hundred forty women were enrolled, and 216 were deemed eligible. Biweekly intravenous dactinomycin 1.25 mg/m² was statistically superior to weekly intramuscular (IM) methotrexate 30 mg/m² (CR: 70% v 53%; P = .01). Similarly, in patients with low-risk GTN as defined before the 2002 WHO risk score revisions (risk score of 0 to 4 and excluding choriocarcinoma), response was 58% and 73% in the methotrexate and dactinomycin arms, respectively (P = .03). Both regimens were less effective if the WHO risk score was 5 or 6 or if the diagnosis was choriocarcinoma (CR: 9% and 42%, respectively). There were two potential recurrences; one at 4 months (dactinomycin) and one at 22 months (methotrexate). Not all patients completed follow-up. Both regimens were well tolerated.
The biweekly dactinomycin regimen has a higher CR rate than the weekly IM methotrexate regimen in low-risk GTN, a generally curable disease.
Abstract Objective To review the literature on fertility-sparing options for women with early stage cervical cancer and outline patient selection criteria, operative, oncologic, and pregnancy ...outcomes. Methods The literature was searched using MEDLINE (OVID: 1950 through October 2009) and EMBASE (OVID: 1988 through October 2009) using combined disease-specific terms (uterine cervix neoplasms/ or cervi:.ti AND cancer:.ti or neoplasms/ or carcinoma:.ti) with treatment-specific term (trachelectomy/). The search was restricted to English or French language and humans. Additionally, Pubmed was searched with terms “cervix”, “carcinoma”, and “trachelectomy”. Reference lists of related articles and recent review articles were also screened for additional citations. Results The largest data on fertility-sparing procedures in early stage cervical cancer has been reported with radical vaginal trachelectomy (RVT). Other fertility-sparing options have emerged recently, such as radical abdominal trachelectomy (RAT). There have been reports of more conservative methods such as simple trachelectomy or cone biopsy, with or without neoadjuvant chemotherapy. Conclusions RVT is now well established as a safe and feasible procedure for this patient population, with low morbidity, recurrence, and mortality rates. The use of RAT in selected patients has increased, in addition to more conservative methods such as simple trachelectomy or cone biopsy, with or without neoadjuvant chemotherapy. Continued research in these areas will determine the safety and feasibility of these potential procedures, which will help give more treatment options for young women with early stage cervical cancers.
Pelvic radiotherapy is an essential component of cancer therapy for patients with cervical and other gynecological malignancies. The ovaries are particularly radiosensitive, and even low radiotherapy ...doses may result in impaired or complete loss of ovarian function, causing hormonal disturbances and infertility. Recent advances in both surgery and radiotherapy have facilitated the ability of some patients to maintain ovarian function through ovarian transposition and careful radiotherapy planning. Multidisciplinary discussions should be undertaken to consider which candidates are appropriate for transposition. Generally, patients under age 35 should be considered due to ovarian reserve, likelihood of oophoropexy success, and radioresistance of ovaries. Those patients with small squamous cell tumors, minimal extra-uterine extension, and no lymphovascular invasion or lymph node involvement are ideal candidates to minimize risk of ovarian metastasis. Patients should be assessed and counseled about the risks of ovarian metastasis and the likelihood of successful ovarian preservation before undergoing oophoropexy and starting treatment. Oophoropexy should be bilateral if possible, and ovaries should be placed superior and lateral to the radiotherapy field. Studies limiting the mean ovarian dose to less than 2-3 Gray have demonstrated excellent preservation of ovarian function. Intensity modulated radiotherapy and volumetric modulated arc therapy techniques have the potential to further minimize the dose to the ovary with excellent outcomes. The addition of brachytherapy to the treatment regimen will probably cause minimal risk to transposed ovaries. Oophoropexy before radiotherapy may preserve the hormonal function of ovaries for a duration, and fertility might be possible through surrogate pregnancy. Successful ovarian transposition has the potential to improve the overall health and wellbeing, reproductive options, and potentially quality of life in patients with cervical and other gynecological cancers.
Abstract Objective To systematically review the existing literature in order to determine the optimal strategy for preoperative identification of the adnexal mass suspicious for ovarian cancer. ...Methods A review of all systematic reviews and guidelines published between 1999 and 2009 was conducted as a first step. After the identification of a 2004 AHRQ systematic review on the topic, searches of MEDLINE for studies published since 2004 was also conducted to update and supplement the evidentiary base. A bivariate, random-effects meta-regression model was used to produce summary estimates of sensitivity and specificity and to plot summary ROC curves with 95% confidence regions. Results Four meta-analyses and 53 primary studies were included in this review. The diagnostic performance of each technology was compared and contrasted based on the summary data on sensitivity and specificity obtained from the meta-analysis. Results suggest that 3D ultrasonography has both a higher sensitivity and specificity when compared to 2D ultrasound. Established morphological scoring systems also performed with respectable sensitivity and specificity, each with equivalent diagnostic competence. Explicit scoring systems did not perform as well as other diagnostic testing methods. Assessment of an adnexal mass by colour Doppler technology was neither as sensitive nor as specific as simple ultrasonography. Of the three imaging modalities considered, MRI appeared to perform the best, although results were not statistically different from CT. PET did not perform as well as either MRI or CT. The measurement of the CA-125 tumour marker appears to be less reliable than do other available assessment methods. Conclusion The best available evidence was collected and included in this rigorous systematic review and meta-analysis. The abundant evidentiary base provided the context and direction for the diagnosis of early-staged ovarian cancer.
To estimate the efficacy and toxicity of AMG 386, an investigational peptide-Fc fusion protein that neutralizes the interaction between the Tie2 receptor and angiopoietin-1/2, plus weekly paclitaxel ...in patients with recurrent ovarian cancer.
Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomly assigned 1:1:1 to receive paclitaxel (80 mg/m(2) once weekly QW, 3 weeks on/1 week off) plus intravenous AMG 386 10 mg/kg QW (arm A), AMG 386 3 mg/kg QW (arm B), or placebo QW (arm C). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, objective response, CA-125 response, safety, and pharmacokinetics.
One hundred sixty-one patients were randomly assigned. Median PFS was 7.2 months (95% CI, 5.3 to 8.1 months) in arm A, 5.7 months (95% CI, 4.6 to 8.0 months) in arm B, and 4.6 months (95% CI, 1.9 to 6.7 months) in arm C. The hazard ratio for arms A and B combined versus arm C was 0.76 (95% CI, 0.52 to 1.12; P = .165). Further analyses suggested an exploratory dose-response effect for PFS across arms (Tarone's test, P = .037). Objective response rates for arms A, B, and C were 37%, 19%, and 27%, respectively. The incidence of grade ≥ 3 adverse events (AEs) in arms A, B, and C was 65%, 55%, and 64%, respectively. Frequent AEs included hypertension (8%, 6%, and 5% in arms A, B, and C, respectively), peripheral edema (71%, 51%, and 22% in arms A, B, and C, respectively), and hypokalemia (21%, 15%, and 5% in arms A, B, and C, respectively). AMG 386 exhibited linear pharmacokinetic properties at the tested doses.
AMG 386 combined with weekly paclitaxel was tolerable, with a manageable and distinct toxicity profile. The data suggest evidence of antitumor activity and a dose-response effect, warranting further studies in ovarian cancer.
PDF
