Thread by @GI_RadOnc

Let's have a closer look 🧐at the PROSPECT trial after its presentation at #ASCO23 and publication in @NEJM bit.ly/43L83oI #radonc #crcsm 1/n

First of all, the study team is to be congratulated for successful recruitment and completion of the study. Almost 1200 patients randomized - everyone who has led a multicenter trial can appreciate how challenging it can be to keep recruitment up over time.

The study enrolled patients with locally advanced rectal cancer that had to meet some specific inclusion criteria.
🔹Tumor located 5-12 cm from anal verge
🔹Sphincter sparing surgery possible at baseline
🔹Distance from MRF min. 3 mm
🔹T2N1 or T3N- or T3 N1
Exclusion:
♦️T4

In the distal rectum I see only very few such patients in particular with the "3 mm definition" for MRF. Also for the mid-rectum I would not expect too many. Indeed, these ~1200 pts. were recruited at ~250 sites over 6 years, which is less than 1 pat. per site per year on avg.

Another relevant aspect: For N1 a single lymph node with a 5 mm diameter in short axis was enough (s. appendix). With this definition the positive predictive value is only 55% ( 👉bit.ly/43rTx5F). Most guidelines rec. the consideration of morphological criteria.

Unfortunately no information about infiltration depth is provided (T3a/b/c/d). However there is a hint that these were mostly smaller T3 tumors: patients in the RtChx arm had a pCR rate of 25% which we usually don't see after RtChx and surgery after a median of 8 wks.

Patients were randomized 1:1
Standard arm: RtChx with 5FU and 50.4 Gy, IMRT or 3D CRT
Standard arm: Experimental arm consisting of 6 cycles of mFOLFOX6
In both arms surgery was planned after pre-OP treatment.
The goal was to prove non-inferiority of Chx in terms of DFS

What did PROSPECT find? The primary endpoint was met, Chx is non-inferior to RtChx.
👉 pCR rate: 24.3% (RtChx) vs. 21.9& (FOLFOX)
👉 5y-DFS 78.6% (RtChx) vs. 80.8% (FOLFOX)
👉 acute G3 toxicity 22.8% (RtChx) vs. 41% (FOLFOX)
👉 acute G4 toxicity 8.9% (RtChx) vs. 2.4% (FOLFOX)

Where do we go from here?
1) Does PROSPECT eliminate from rectal cancer? No.
2) Does it offer a new treatment option? Yes, for a very small subgroup of pts. with LARC.
3) Will it change my practice: No.

Why?

Many of the patients included in the trial had "low-risk" rectal tumors and several guidelines were actually already considering these for primary surgery without any pre-OP treatment.
bit.ly/3OWpjDk
Both arms in PROSPECT are overtreatment for these patients.

Tx of rectal cancer is a lot more complex than 10 years ago when it was "one size fits all".
Today we know that we have to esc. some (TNT+Surgery) and on the other hand can deesc. others by omitting RT, surgery or chx.
Interdisc. discussion and consultation of our pts. is key!