Publications Update # 103

Non-Medical Article of the Week

What Is the Purpose of Your Purpose?

“Despite its sudden elevation in corporate life,” the authors write, “purpose remains a confusing topic.” They argue that a primary cause of this confusion is that the word is used in three senses: Cause -based purposes (such as Patagonia’s “in business to save our home planet”) tend to receive the most attention. Competence -based purposes (such as Mercedes’s “First Move the World”) express a clear value proposition to customers and the employees responsible for delivering that value. Culture -based purposes (such as Zappos’s “To Live and Deliver WOW”) are effective at creating internal alignment and collaboration with key partners. The authors offer advice about identifying what sort of purpose will best suit your company without misrepresenting it.

Harvard Business ReviewJonathan Knowles

For the fellows graduating and joining new practices - Don’t hand your purpose to the new employer or their marketing team—own it. Find the path that fits you niche: competence (outstanding clinical care), culture (how you work together), or cause (a social mission). Pick what rings true, put it in writing, then prove it—perform, and lead in ways that back it up. Many practices thrive by doubling down on clinical excellence or a strong culture; you don’t need a grand crusade unless it’s genuine. Purpose only matters when you—and your team—model it in every consult, hand-off, and decision. This HBR article is a great read.

Cervical Cancer

In the seven-plus years since the LACC trial, I have yet to meet a single patient willing to accept a higher risk of recurrence just to have her radical hysterectomy done minimally invasively. For most of us, that debate was over—pending the ROCC and RACC trials, which might resurrect a very different, rigorously vetted MIS radical hysterectomy if they can prove true non-inferiority to the open approach.
Then came the SHAPE trial, and it muddied the waters. Remember: 83% of cases in the simple-hysterectomy arm and 71% in the radical-hysterectomy arm were performed minimally invasively (MIS). The investigators themselves warned us not to over-extrapolate and stay away from “MIS is safe for simple hysterectomy in cervical cancer” narrative as the trial was not powered to detect this difference. After getting burned by unvalidated MIS in this disease once already, that caution felt warranted.
Fast-forward to today’s featured paper: KGOG compared MIS with open simple hysterectomy in patients who fit SHAPE criteria. The disease-free survival 55 months vs 66.5 months, and pelvic recurrences 6% vs 2% (both p < 0.05) in favor of open surgery once again reemphasize the fact that MIS (without the cautions built in ROCC and RACC trials) in cervical cancer is definitely NOT safe.

T.L;D.R: Until we see solid evidence to the contrary, I’m sticking with—and strongly recommending—open simple hysterectomy for cervical-cancer patients meeting SHAPE criteria for simple hysterectomy, especially those with residual cervical disease.

Oncologic outcomes of minimally invasive surgery vs. abdominal hysterectomy in patients with low-risk, early-stage cervical cancer: A retrospective analysis of KGOG 1028 data based on SHAPE trial eligibility criteria - PubMed

Even in low-risk, early-stage cervical cancer patients meeting SHAPE trial criteria, MIS was associated with shorter DFS and a higher pelvic recurrence risk than abdominal hysterectomy. These findings are consistent with concerns raised by the LACC trial, suggesting a potential oncologic disadvantag …

PubMedJaekyung Bae

Related Content on GYOEDU
Read about how to reduce the risk of recurrence in cervical cancer patients undergoing radical hysterectomy by first performing conization before surgery (from Publications Update # 99)

Endometrial Cancer

Pragmatic preoperative molecular classification of endometrial cancers; Replacing POLE sequencing with hormone receptor staining - PubMed

Preoperative evaluation of ER, PR, MMR and p53 identifies four molecular and prognostic groups. This pragmatic classification allows POLE sequencing to be omitted. Our proposed algorithm saves time and resources and is a valuable alternative to full molecular classification.

PubMedHege F Berg

Pragmatic molecular classification has the potential to replace expensive genomic sequencing with four pre-operative immunohistochemistry stains (MMR, p53, ER, PR). In this paper, Berg et al. demonstrated that their IHC algorithm stratifies endometrial cancers into MMR-d, p53-abn, HR-low, and HR-high groups, achieving prognostic separation equivalent to the TCGA/ProMisE model, while eliminating routine POLE testing and delivering results before surgery based on endometrial biopsies.

How to think about this paper?
Here is how these groups map onto each other. Primarily, the POLE group overlaps heavily with the MMR-p, p53wt, and hormone receptor-high group.

Previously, I sent a different paper in the Publications Update # 86 with a very similar idea of pragmatic molecular testing in endometrial cancer. The difference in this paper is that the authors used ER receptor only instead of a combination of ER/PR.

Less is more? Comparison between genomic profiling and immunohistochemistry-based models in endometrial cancer molecular classification: A multicenter, retrospective, propensity-matched survival analysis - PubMed

The IHC-M showed overlapping classification performance compared to the GP-M in terms of oncologic outcomes. This study may lay the basis to further investigate the real-life clinical impact of POLE sequencing in molecular classification and the potential stand-alone prognostic role of ER status for …

PubMedEmanuele Perrone

A video explaining the Less is More approach was previously sent in Publications Update # 86. Watch a video explaining the paper

A similar breakdown of the categories for Perrone et al

In other words, POLE mut can be infered by the hormone receptor status to a very high degree based on these two papers. Patients with best prognosis are MMR-p, p53-wt, high-hormone receptor

Question(s) from the Question Bank

Question 1

A 70-year-old woman with a history of persistent cough and active smoking is scheduled for an open exploratory laparotomy and debulking for suspected advanced ovarian cancer. Preoperative pulmonary function tests are obtained. Which single preoperative pulmonary function test parameter is MOST predictive of an increased risk for major postoperative pulmonary complications (e.g., pneumonia, respiratory failure) in this patient?

A. Forced Vital Capacity (FVC) less than 70% predicted.
B. Forced Expiratory Volume in 1 second (FEV1) less than 1.0-1.5 liters or <50% predicted.
C. Peak Expiratory Flow Rate (PEFR) below 200 L/min.
D. Diffusing capacity of the lung for carbon monoxide (DLCO) less than 60% predicted.
E. Residual Volume (RV) to Total Lung Capacity (TLC) ratio greater than 40%.

Question 2

A 62-year-old woman is diagnosed with a 6-cm midline squamous cell carcinoma of the vulva. Because a primary radical resection would require a permanent colostomy, the tumor board recommends treating the vulvar tumour with primary chemoradiation to facilitate sphincter preservation. Pre-treatment 18F-FDG PET/CT shows avid uptake in the right groin lymph node; the left groin is clinically and radiographically negative. The patient is medically fit for surgery and agrees to any indicated nodal procedure before starting chemoradiation. Which groin-node strategy offers the highest chance of regional control with acceptable morbidity?

A. Bilateral sentinel-lymph-node dissection only, then chemoradiation
B. Right inguinofemoral dissection with left sentinel dissection, then chemoradiation
C. Bilateral complete inguinofemoral lymph-node dissections, followed by chemoradiation
D. Definitive chemoradiation to vulva and bilateral groins without nodal surgery
E. Right-groin radiation boost to 60 Gy without nodal surgery; observe the left groin

Answer(s)

Pulmonary Function Testing

Answer 1: B
Explanation:
While multiple parameters from pulmonary function tests (PFTs) can indicate risk, a significantly reduced Forced Expiratory Volume in 1 second (FEV1) is one of the strongest predictors of postoperative pulmonary complications, particularly after major abdominal or thoracic surgery.
Values less than 1.0-1.5 liters or less than 50% of predicted are often cited as indicating high risk. In the prospective, single-centre PREDICT study, 320 adults with known or suspected COPD who were scheduled for major non-cardiac surgery underwent routine spirometry in addition to a standard pre-operative assessment. In multivariable modelling, the only spirometric variable retained was %-predicted FEV₁, which remained an independent risk factor.
According to the PREDICT study, full PFTs add cost and inconvenience without any benefit.

A low FVC (A) also indicates restrictive or obstructive defects, but FEV1 is often more emphasized for postoperative risk. PEFR (C) measures large airway function. DLCO (D) reflects gas exchange capacity and serves as a predictor, but FEV1 often stands out as a more reliable predictor of overall pulmonary complications related to airway clearance and ventilatory capacity. An increased RV/TLC ratio (E) indicates air trapping, which is common in COPD; however, FEV1 is a more direct measure of expiratory airflow limitation relevant to postoperative events.

Preoperative Spirometry in Patients With Known or Suspected Chronic Obstructive Pulmonary Disease Undergoing Major Surgery: The Prospective Observational PREDICT Study - PubMed

COPD is underdiagnosed in surgical patients. Patients with newly diagnosed COPD commonly presented with low GOLD severity grades and were not at higher risk for PPC. Neither a structured COPD-specific assessment nor preoperative PFTs added incremental diagnostic value to the standard clinical preass …

PubMedAndré Dankert

A “full” pulmonary-function test (PFT) panel typically includes all of the following individual tests:

1. Baseline (pre-bronchodilator) spirometry
2. Post-bronchodilator reversibility spirometry
3. Lung-volume measurement (body plethysmography or helium/nitrogen wash-out)
4. Diffusing-capacity test for carbon monoxide (DLCO/TLCO)
5. Airway resistance / specific airway conductance (Raw, sGaw)
6. Maximal voluntary ventilation (MVV)
7. Respiratory-muscle pressures – maximal inspiratory & expiratory pressures (MIP/MEP)
8. Fractional exhaled nitric oxide (FeNO) – airway-inflammation marker
9. Bronchial provocation/challenge test (e.g., methacholine, mannitol or exercise)
10. Resting or post-exercise arterial (or arterialised capillary) blood-gas analysis / pulse-oximetry

However, according to the PREDICT study, only SPIROMETRY is predictive of postoperative pulmonary complications. Therefore, in these patients, there is no need to order the FULL PFT; only order spirometry.

Vulvar Cancer

Node-positive carcinoma of the vulva treated with curative-intent radiotherapy - PubMed

Locoregional control and overall survival were highest in patients treated with surgery followed by radiotherapy. Definitive chemoradiotherapy provided moderate disease control and survival outcomes in patients unfit for surgery, supporting its use as an alternative treatment strategy.

PubMedJulianne O’Shea

Management Algorithm for Groin-Node–Positive Vulvar Cancer

1. Clinically Negative or PET-Negative Groins (cN0)

2. PET-Avid or Clinically Enlarged/Fixed Groins (cN+)

Important Considerations

• Bilateral treatment: cover both groins unless the primary is clearly lateralised and the contralateral SLN is negative.
• Pelvic RT trigger: initiate pelvic fields when ≥ 2 inguinal nodes are positive.
• Manage Toxicity: early physiotherapy, compression garments, and meticulous RT planning limit lymphedema; grade ≥ 3 late effects remain uncommon.

Answer 2: C

If this patient were medically inoperable, the chemoradiation to the groin is an acceptable alternative, but it has a lower 5-year survival. Here is a table of all the studies focusing specifically on the groins:

Radiation dose-response evidence for node-positive groins in vulvar cancer

†Elective groin/pelvic volumes generally received 45–50 Gy; the table lists the dose prescribed to grossly involved inguinal nodes or sentinel-node basin.

Patterns across studies

• Locoregional control consistently improves once the nodal dose surpasses ~60 Gy, especially with concurrent platinum.
• Surgical debulking followed by 50–55 Gy adjuvant RT still provides the best long-term control when surgery is feasible.
• For micrometastatic disease (≤2 mm), 50 Gy alone achieves >98 % groin control and spares full dissection morbidity.
• Dose-escalated IMRT/VMAT (≥64 Gy) yields ≥70 % pathologic CR but at the cost of higher acute grade 3-4 toxicity; careful patient selection is essential.

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That's it for this week. Next week, ASCO 2025 edition!