Sentinel Nodes for Endometrial Cancer

In Lancet Oncology

Results of a sentinel node lymph node biopsy in endometrial cancer are published, and they report a high NPV. Though it is buried in the paper, the sensitivity was 84%, which is a little bit lower than other SNLB series. As I count it, there were 3 patients who had a negative SLNB out of a total of 20 patients with nodal positivity, for a false negative rate of 15%.

This is a little less compelling than the more established vulvar sentinel studies, or the more recently reported cervical cancer series, but does raise some interesting possibilities. As the utility of dissection is debatable in endometrial cancer (as opposed to vuvla or cervix) - is a simple, less morbid, though admittedly less accurate means of staging "good enough?"

Link:

[Articles] Detection rate and diagnostic accuracy of sentinel-node biopsy in early stage endometrial cancer: a prospective multicentre study (SENTI-ENDO): "SLN biopsy with cervical dual labelling could be a trade-off between systematic lymphadenectomy and no dissection at all in patients with endometrial cancer of low or intermediate risk. Moreover, our study suggests that SLN biopsy could provide important data to tailor adjuvant therapy."

Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer

In the NEJM

An update to the Scandinavian randomized trial of Prostatectomy vs Watchful Waiting appears in the NEJM this week. Very useful for it's delineation of the natural history of early stage prostate cancer and the expected results with radical local therapy. Of course, it is impossible to know what the results of brachytherapy or EBRT would be in comparison to RP; nonetheless, it gives one ballpark numbers when counseling patients on their options.

Link:

Radical Prostatectomy versus Watchful Waiting in Early Prostate Cancer: New England Journal of Medicine, Volume 364, Issue 18, Page 1708-1717, May 2011.

Long term toxicity of WPRT for endometrial cancer (results of PORTEC 1)

In the JCO

Long term toxicity data for the PORTEC 1 trial sees manuscript publication (previously presented at ASTRO 2 years ag0). Worth a read, as the investigators find significant long term toxicity from WPRT. These results should be taken with some caveats however, as the surveys were sent out after the fact (only 351 surveys were sent out, of 714 in the full trial, and there was a 70% responsed rate for those 351). This raises the question of recall and selection bias. One can easily speculate that the patients continuing in followup were those that had complications. Additionally, one could also speculate that one is more likely to answer a QOL survey if one has significant symptoms.

That said, this should give the practicing radiation oncologist pause when recommending WPRT if there are alternatives (VBT) or a low risk of recurrence even in the absence of adjuvant therapy.

Link and Abstract:

Long-Term Outcome and Quality of Life of Patients With Endometrial Carcinoma Treated With or Without Pelvic Radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) Trial [Gynecologic Cancer]: "Purpose

To determine the long-term outcome and health-related quality of life (HRQL) of patients with endometrial carcinoma (EC) treated with or without pelvic radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) trial.

Patients and Methods

Between 1990 and 1997, 714 patients with stage IC grade 1 to 2 or IB grade 2 to 3 EC were randomly allocated to pelvic external-beam radiotherapy (EBRT) or no additional treatment (NAT). HRQL was evaluated with the Short Form 36-Item (SF-36) questionnaire; subscales from the European Organisation for Research and Treatment of Cancer (EORTC) PR25 module for bowel and bladder symptoms and the OV28 and CX24 modules for sexual symptoms; and demographic questions. Analysis was by intention-to-treat.

Results

Median follow-up was 13.3 years. The 15-year actuarial locoregional recurrence rates were 5.8% for EBRT versus 15.5% for NAT (P < .001), and 15-year overall survival was 52% versus 60% (P = .14). Of the 351 patients confirmed to be alive with correct address, 246 (70%) returned the questionnaire. Patients treated with EBRT reported significant (P < .01) and clinically relevant higher rates of urinary incontinence, diarrhea, and fecal leakage leading to more limitations in daily activities. Increased symptoms were reflected by the frequent use of incontinence materials after EBRT (day and night use, 42.9% v 15.2% for NAT; P < .001). Patients treated with EBRT reported lower scores on the SF-36 scales "physical functioning" (P = .004) and 'role-physical' (P = .003).

Conclusion

EBRT for endometrial cancer is associated with long-term urinary and bowel symptoms and lower physical and role-physical functioning, even 15 years after treatment. Despite its efficacy in reducing locoregional recurrence, EBRT should be avoided in patients with low- and intermediate-risk EC.

"

Sentinel Nodes in Cervical Cancer

In the JCO

Sentinel node mapping is making an appearance in all of the gynecologic cancers, most notably vulvar cancer, however two recent studies have examined the technique in cervix and endometrial cancer. The current study is in IA1-IB1 cervical lesions undergoing surgical staging and management, all of who were evaluated with a SNLB and then with a full dissection. The false negative rate was 8% (2/25), which is similar to the experience in breast. The investigators also noted that if bilateral nodes were mapped, there were no false negatives, but I would apply that with some caution as it appears to be a post hoc analysis.

While the rate false negative rate is similar to breast cancer, it remains to be seen if the clinical results will be the same as breast cancer. While this is a great step in the path towards integrating this into the management of early cervical cancer, one awaits a clinical trial in which the completion dissection is not performed, with careful follow up of the results. One must also be mindful of what we are actually accomplishing by performing less extensive dissections - while there are some adverse events associated with pelvic and PA dissections, in general they are relatively rare. The benefit of less extensive nodal sampling is much clearer in vulvar and breast cancer, where the risk of morbidity due to lymphedema is correspondingly higher.

Link and Abstract:

Bilateral Negative Sentinel Nodes Accurately Predict Absence of Lymph Node Metastasis in Early Cervical Cancer: Results of the SENTICOL Study [Gynecologic Cancer]: "Purpose

Sentinel lymph node (SLN) biopsy may be used to target lymph node metastases in patients with early cervical cancer. Whether SLN biopsy only is acceptable in the staging and surgical management of early cervical cancer remains unknown. This prospective multicenter study (SENTICOL [Ganglion Sentinelle dans le Cancer du Col]) assessed the sensitivity and negative predictive value (NPV) of SLN biopsy.

Patients and Methods

Adults with cervical carcinoma who met the International Federation of Gynecology and Obstetrics criteria for stage IA1 with lymphovascular space invasion to stage IB1 underwent technetium 99 lymphoscintigraphy and Patent Blue injection followed by laparoscopic lymph node mapping, SLN removal, and lymph node dissection. Only surgeons trained in SLN biopsy in cervical carcinoma participated in the study. SLNs and nonsentinel lymph nodes underwent routine staining. Negative SLNs were subjected to ultrastaging. The reference method was pelvic and/or para-aortic lymphadenectomy with histologic examination of all nodes.

Results

One hundred forty-five patients were enrolled, and 139 were included in a modified intention-to-diagnose analysis. Intraoperative radioisotope-blue dye mapping detected at least one SLN in 136 patients (97.8%; 95% CI, 93.8% to 99.6%), 23 of whom had true-positive results and two who had false-negative results, yielding 92.0% sensitivity (23 of 25; 95% CI, 74.0% to 99.0%) and 98.2% NPV (111 of 113; 95% CI, 74.0% to 99.0%) for node metastasis detection. No false-negative results were observed in the 104 patients (76.5%) in whom SLN were identified bilaterally.

Conclusion

Combined labeling for node mapping was associated with high rates of SLN detection and with high sensitivity and NPV for metastasis detection. However, SLN biopsy was fully reliable only when SLNs were detected bilaterally.

"

Gem + CDDP + RT with adjuvant CDDP + Gem vs standard CTRT for cervical cancer

In the JCO:

I posted previously about this trial from Argentina when presented at ASCO 2 years ago, now the manuscript is published in the JCO. Essentially this trial asks two questions, the utility of concurrent gem with CDDP, and the utility of adjuvant chemotherapy. The overall effect is compelling in this manuscript, improved local control, DFS and OS, compared to standard CTRT with brachy, albeit at the cost of increased toxicity. I don't feel that a change in standard practice will occur in the US yet due to these results, as most US practitioners would like a confirmatory trial, preferably examining the gem question and the adjuvant chemo question separately. That said, for certain high risk patients, some of the Gynecologic Oncologists I work with have been giving adjuvant chemotherapy (CDDP based) due in part to these results.

Link and Abstract.

Phase III, Open-Label, Randomized Study Comparing Concurrent Gemcitabine Plus Cisplatin and Radiation Followed by Adjuvant Gemcitabine and Cisplatin Versus Concurrent Cisplatin and Radiation in Patients With Stage IIB to IVA Carcinoma of the Cervix [Gynecologic Cancer]: "Purpose

To determine whether addition of gemcitabine to concurrent cisplatin chemoradiotherapy and as adjuvant chemotherapy with cisplatin improves progression-free survival (PFS) at 3 years compared with current standard of care in locally advanced cervical cancer.

Patients and Methods

Eligible chemotherapy- and radiotherapy-naive patients with stage IIB to IVA disease and Karnofsky performance score ≥ 70 were randomly assigned to arm A (cisplatin 40 mg/m² and gemcitabine 125 mg/m² weekly for 6 weeks with concurrent external-beam radiotherapy [XRT] 50.4 Gy in 28 fractions, followed by brachytherapy [BCT] 30 to 35 Gy in 96 hours, and then two adjuvant 21-day cycles of cisplatin, 50 mg/m² on day 1, plus gemcitabine, 1,000 mg/m² on days 1 and 8) or to arm B (cisplatin and concurrent XRT followed by BCT only; dosing same as for arm A).

Results

Between May 2002 and March 2004, 515 patients were enrolled (arm A, n = 259; arm B, n = 256). PFS at 3 years was significantly improved in arm A versus arm B (74.4% v 65.0%, respectively; P = .029), as were overall PFS (log-rank P = .0227; hazard ratio [HR], 0.68; 95% CI, 0.49 to 0.95), overall survival (log-rank P = .0224; HR, 0.68; 95% CI, 0.49 to 0.95), and time to progressive disease (log-rank P = .0012; HR, 0.54; 95% CI, 0.37 to 0.79). Grade 3 and 4 toxicities were more frequent in arm A than in arm B (86.5% v 46.3%, respectively; P < .001), including two deaths possibly related to treatment toxicity in arm A.

Conclusion

Gemcitabine plus cisplatin chemoradiotherapy followed by BCT and adjuvant gemcitabine/cisplatin chemotherapy improved survival outcomes with increased but clinically manageable toxicity when compared with standard treatment.

"

JCO long term follow up of Tamoxifen

In the JCO:

A very interesting article on the long term benefits of tamoxifen for breast cancer patients, emphasizing the curative nature of adjuvant hormone modulation in breast cancer patients. Also of interest is the reduction in CV events with longer term tamoxifen and the stability of the endometrial cancer risk at ~1.5% for both.

Link and Abstract:

Long-Term Benefits of 5 Years of Tamoxifen: 10-Year Follow-Up of a Large Randomized Trial in Women at Least 50 Years of Age With Early Breast Cancer [Breast Cancer]: "Purpose

The Cancer Research UK 'Over 50s' trial compared 5 and 2 years of tamoxifen in women with early breast cancer. Results are reported after median follow-up of 10 years.

Patients and Methods

Between 1987 and 1997, 3,449 patients age 50 to 81 years with operable breast cancer who had been taking 20 mg of tamoxifen for 2 years were randomly assigned to either stop or continue for an additional 3 years, if they were alive and recurrence free. Data on recurrences, new tumors, deaths, and cardiovascular events were obtained (April 2010).

Results

There were 1,103 recurrences, 755 deaths as a result of breast cancer, 621 cardiovascular (CV) events, and 236 deaths as a result of CV events. Fifteen years after starting treatment, for every 100 women who received tamoxifen for 5 years, 5.8 fewer experienced recurrence, compared with those who received tamoxifen for 2 years. The risk of contralateral breast cancer was significantly reduced (hazard ratio, 0.70; 95% CI, 0.48 to 1.00). Among women age 50 to 59 years, there was a 35% reduction in CV events (P = .005) and 59% reduction in death as a result of a CV event (P = .02); in older women, the effect was much smaller and not statistically significant.

Conclusion

Taking tamoxifen for the recommended 5 years reduces the risk of recurrence or contralateral breast cancer 15 years after starting treatment. It also lowers the risk of CV disease and death as a result of a CV event, particularly among those age 50 to 59 years. Women should therefore be encouraged to complete the full course. Although aromatase inhibitors improve disease-free survival, tamoxifen remains a cheap and highly effective alternative, particularly in developing countries.

"

3mo, 6 mo or no ADT for locally advance prostate cancer

Lancet Oncology this month:

The TROG investigators have published 10 year results of their no ADT, 3mo ADT, vs 6mo ADT, 3 armed randomized trial. The results show that while there are some benefits to 3mo ADT (such as decreased PSA recurrences, and improved DFS), but the larger benefits (distant metastases and overall survival) only became significant with 6 month. Of note, the majority of these patients were high risk, so the EORTC trial would already suggest that even 6months treatment doesn't give the full benefit, but, nonetheless, it does appear that even a few more months add benefit.

Link