PCa study evaluates ‘clinically meaningful’ margins, recurrence

“Journal Article of the Month” is a new Urology Times section in which Badar M. Mian, MD (left), offers perspective on noteworthy research in the peer-reviewed literature. Dr. Mian is professor of surgery in the division of urology at Albany Medical College, Albany, NY.

After prostatectomy, the presence of positive surgical margins is a well-established risk factor for biochemical (PSA) recurrence (BCR). However, the association of BCR with metastases and the optimal timing of subsequent, adjuvant, or salvage treatment remain unclear. Research from Martini et al indicates that most PSMs do not result in clinical recurrence or metastases, except in those with additional significant risk factors (Eur Urol Oncol 2019 [in press]).

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The authors analyzed 1,757 patients treated with prostatectomy between 2011 and 2017 who had not received any neoadjuvant or adjuvant therapies. Their clinical characteristics were in line with other prostatectomy cohorts. Of these, 285 (16%) had PSMs of variable extent, length, and focality. A total of 406 patients (23%) had aggressive pathologic features (>pT3b and/or lymph node involvement [LNI] and/or grade group 4-5) and had a higher rate of PSMs, as expected.

During a relatively short median follow-up period of 36 months, 202 patients experienced BCR, 29 of whom progressed to clinical recurrence. Overall, the 5-yr BCR-free and clinical recurrence-free survival rates were 79% and 96%, respectively. The presence of PSMs, the number of PSMs, and PSM length were predictors of BCR (p=.02), while only those patients with multifocal or long PSMs were associated with the risk of clinical recurrence (p<.04).

Next: Margins categorized as favorable, unfavorableMargins categorized as favorable, unfavorable

The authors divided the PSMs into two groups: favorable, defined as a single margin of <3 mm, and unfavorable, defined as multifocal or >3 mm PSM. Overall, 120 patients (42%) had favorable PSMs and 165 patients (58%) had unfavorable PSMs. The 5-year BCR-free survival rates for patients without PSMs, patients with favorable PSMs, and patients with unfavorable PSMs were 81%, 71%, and 61%, (p<.002), respectively. Similarly, the clinical recurrence-free survival rates for patients without PSMs, patients with favorable PSMs, and patients with unfavorable PSMs were 98%, 97%, and 89% (p=.002), respectively.

The authors noted that patients with both features; ie, the aggressive pathologic characteristics (pT3b/4 and/or grade group 4-5 and/or LNI) and the unfavorable PSMs (multifocal or >3 mm), had increased risk of biochemical and clinical recurrence. For this group with multiple adverse pathologic features, the 5-year BCR-free survival rates for patients without PSMs, patients with favorable PSMs, and patients with unfavorable PSMs were 62%, 63%, and 53%. The clinical recurrence-free survival rates for patients without PSMs, patients with favorable PSMs, and those with unfavorable PSMs were 90%, 96%, and 76%.

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Both the European and the American urologic associations recommend adjuvant radiation therapy be administered or be specifically discussed in patients with PSMs. For men who undergo prostatectomy (or any treatment) for prostate cancer, the functional outcomes are often the overriding concern and there is heavy focus on intraoperative and perioperative measures to improve recovery of urinary and sexual function. So the decision about delivering adjuvant treatment (in the absence of cancer or symptoms) is made more complex due to the concerns regarding overtreatment and further worsening the urinary and sexual function. In this study, even if only the higher risk subgroup (unfavorable PSMs and advanced stage/grade) were to receive adjuvant treatment, nearly 75% of patients may potentially be overtreated.

The outcomes of men with PSMs after prostatectomy are quite heterogeneous. Identifying men at highest risk of clinical recurrence and metastases (not just BCR) may allow us to either modify the follow-up protocols to select men for adjuvant or timely salvage therapy. Our ability to prognosticate cancer outcomes based on the usual clinical parameters (grade, stage, margins) is limited. Hopefully, more sophisticated genomic or proteomic tests in the future will allow us to select the correct patients for adjuvant therapy while avoiding overtreatment for majority of the patients.