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Article of the Week: The impact of PSMs on long-term outcomes after RP

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Prabhakar Mithal, discussing his paper.

If you only have time to read one article this week, it should be this one.

Positive Surgical Margins in Radical Prostatectomy Patients Do Not Predict Long-term Oncological Outcomes: Results from SEARCH

 

Prabhakar Mithal, Lauren E. Howard†‡, William J. Aronson§, Martha K. Terris**††Matthew R. Cooperberg‡‡, Christopher J. Kane§§, Christopher Amling¶¶ and Stephen J. Freedland***

 

Department of Urology, University of Rochester Medical Center, Rochester, NY, Department of Biostatistics and Bioinformatics, Duke University School of MedicineDivision of Urology, Veterans Affairs Medical Center, Durham, NC, §Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare SystemDepartment of Urology, UCLA School of Medicine, Los Angeles, CA, **Section of Urology, Veterans Affairs Medical Center††Section of Urology, Medical College of Georgia, Augusta, GA, ‡‡Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, §§Urology Department, University of California San Diego Health System, San Diego, CA ¶¶Division of Urology, Department of Surgery, Oregon Health and Science University, Portland, OR , and ***Division of Urology, Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA, USA

 

Objective

To assess the impact of positive surgical margins (PSMs) on long-term outcomes after radical prostatectomy (RP), including metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM).

Patients and Methods

Retrospective study of 4 051 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort treated by RP from 1988 to 2013. Proportional hazard models were used to estimate hazard ratios (HRs) of PSMs in predicting biochemical recurrence (BCR), CRPC, metastases, and PCSM. To determine if PSMs were more predictive in certain patients, analyses were stratified by pathological Gleason score, stage, and preoperative prostate-specific antigen (PSA) level.

FebAOTW4

Results

The median (interquartile range) follow-up was 6.6 (3.2–10.6) years and 1 127 patients had >10 years of follow-up. During this time, 302 (32%) men had BCR, 112 (3%) developed CRPC, 144 (4%) developed metastases, and 83 (2%) died from prostate cancer. There were 1 600 (40%) men with PSMs. In unadjusted models, PSMs were significantly associated with all adverse outcomes: BCR, CRPC, metastases and PCSM (all ≤ 0.001). After adjusting for demographic and pathological characteristics, PSMs were associated with increased risk of only BCR (HR 1.98, < 0.001), and not CRPC, metastases, or PCSM (HR ≤1.29, > 0.18). Similar results were seen when stratified by pathological Gleason score, stage, or PSA level, and when patients who underwent adjuvant radiotherapy were excluded.

Conclusions

PSMs after RP are not an independent risk factor for CRPC, metastasis, or PCSM overall or within any subset. In the absence of other high-risk features, PSMs alone may not be an indication for adjuvant radiotherapy.

Editorial: Should we worry about positive surgical margins in prostate cancer?

The debate on the impact of positive surgical margins (PSMs) after radical prostatectomy (RP) continues. The study by Mithal et al. [1] in the present issue contributes further data to an extensive and growing body of literature addressing the clinical significance of a PSM after RP, and ultimately alludes to the question of how to manage these patients.

The authors [1] use the SEARCH database, a large dataset comprised of patients from multiple Veterans Affairs Medical Centers across the USA, to collect and report data on oncological outcomes of PSMs after RP. After adjusting for demographic and pathological confounders, use of adjuvant therapy, and the competing risk of non-prostate-cancer-related death, PSMs were significantly associated with an increased hazard of biochemical recurrence (BCR; hazard ratio 1.99, 95% CI 1.76–2.26), but not castrate resistant prostate cancer (CRPC), metastases, or mortality (prostate-cancer specific or overall). The current study [1], takes such analysis a step further and reports that PSMs were not associated with a negative impact on hard clinical outcomes (CRPC, metastasis, and prostate cancer-specific mortality [PCSM]) in those subgroups at the highest risk of disease progression (high Gleason stage, T-stage, and PSA level). These findings are not necessarily novel, but rather consistent with much of the prior literature. The detrimental impact of PSMs on BCR is well documented [2]. However, the impact of PSMs on hard clinical outcomes such as CRPC, metastasis, and PCSM has not been well demonstrated, despite multiple studies with large cohorts and extensive follow-up.

The negative consequence of a PSM on long-term patient outcome is a very intuitive concept, as it indicates cancer has been inadequately resected or ‘left behind’. Furthermore, the negative impact of a PSM on hard clinical outcomes is well established in many surgically treated malignancies. However, in prostate cancer there remains a disconnect between PSMs and hard clinical outcomes. The authors of the current study [1] provide further evidence to reiterate that the course of this disease after a PSM is not absolute, immediate, or even necessarily concerning (at least in the intermediate follow-up). A PSM after RP may increase the likelihood of BCR but this does not necessarily equal imminent progression and/or death.

PSMs are reported in 10–31% of patients undergoing RP, thus emphasising the clinical importance of this question [3, 4]. Despite the current findings [1], PSMs should not be dismissed. The management of a PSM after RP remains complicated. A proportion of patients will progress and succumb to this disease and, furthermore, therapeutic interventions with shown benefit are available to address such concerns. The decision on how aggressively to manage PSMs may involve an understanding of the patient (comorbidities, lifestyle, and preferences) along with an informed discussion. Furthermore, other pathological details not captured in this study [1] (tumour margin extent and location) [5, 6], along with longer follow-up may be important in identifying drivers for this disease and how to better stratify patients. As with many clinical questions, the approach to PSMs after RP is not necessarily clearly defined and may not apply similarly to all patients across the board. This study [1] may not answer whether or not we should worry about PSMs in prostate cancer, but contributes to our ability to develop clinical algorithms and informed decisions in these patients.

 

Stanley A. Yap
Department of Urology, University of California Davis Medical Center, 4860 Y Street, Suite 3500, Sacramento, CA, 95817,
USA

 

References

 

Video: PSMs in RP patients do not predict long-term oncological outcomes

Positive Surgical Margins in Radical Prostatectomy Patients Do Not Predict Long-term Oncological Outcomes: Results from SEARCH

Prabhakar Mithal, Lauren E. Howard†‡, William J. Aronson§, Martha K. Terris**††Matthew R. Cooperberg‡‡, Christopher J. Kane§§, Christopher Amling¶¶ and Stephen J. Freedland***

 

Department of Urology, University of Rochester Medical Center, Rochester, NY, Department of Biostatistics and Bioinformatics, Duke University School of MedicineDivision of Urology, Veterans Affairs Medical Center, Durham, NC, §Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare SystemDepartment of Urology, UCLA School of Medicine, Los Angeles, CA, **Section of Urology, Veterans Affairs Medical Center††Section of Urology, Medical College of Georgia, Augusta, GA, ‡‡Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, §§Urology Department, University of California San Diego Health System, San Diego, CA ¶¶Division of Urology, Department of Surgery, Oregon Health and Science University, Portland, OR , and ***Division of Urology, Department of Surgery, Cedars Sinai Medical Center, Los Angeles, CA, USA

 

Objective

To assess the impact of positive surgical margins (PSMs) on long-term outcomes after radical prostatectomy (RP), including metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM).

Patients and Methods

Retrospective study of 4 051 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort treated by RP from 1988 to 2013. Proportional hazard models were used to estimate hazard ratios (HRs) of PSMs in predicting biochemical recurrence (BCR), CRPC, metastases, and PCSM. To determine if PSMs were more predictive in certain patients, analyses were stratified by pathological Gleason score, stage, and preoperative prostate-specific antigen (PSA) level.

FebAOTW4

Results

The median (interquartile range) follow-up was 6.6 (3.2–10.6) years and 1 127 patients had >10 years of follow-up. During this time, 302 (32%) men had BCR, 112 (3%) developed CRPC, 144 (4%) developed metastases, and 83 (2%) died from prostate cancer. There were 1 600 (40%) men with PSMs. In unadjusted models, PSMs were significantly associated with all adverse outcomes: BCR, CRPC, metastases and PCSM (all ≤ 0.001). After adjusting for demographic and pathological characteristics, PSMs were associated with increased risk of only BCR (HR 1.98, < 0.001), and not CRPC, metastases, or PCSM (HR ≤1.29, > 0.18). Similar results were seen when stratified by pathological Gleason score, stage, or PSA level, and when patients who underwent adjuvant radiotherapy were excluded.

Conclusions

PSMs after RP are not an independent risk factor for CRPC, metastasis, or PCSM overall or within any subset. In the absence of other high-risk features, PSMs alone may not be an indication for adjuvant radiotherapy.

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