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SUO 2024: Joseph A Smith, Jr. Mentorship Award Lecture

(UroToday.com) The 2024 Society of Urologic Oncology (SUO) annual meeting held in Dallas, between December 3 and December 6, 2024, was host to the Joseph A Smith, Jr. Mentorship Award Lecture. by Dr. Christopher Kane.

Dr. Kane began his presentation by highlighting some of the attributes he admires in Dr. Smith and aspires to embody himself. Dr. Smith is known for leading from the front, being a thoughtful leader, and showing generosity by promoting others from a mentorship perspective. He is famously fit and balanced, highly efficient in surgery and leadership, allows others to excel without micromanagement, and is very thoughtful and kind in his interactions.

Dr. Kane described professional development as extending beyond the scope of mentorship. Mentorship involves long-term guidance focused on professional and personal growth. Coaching provides targeted support for specific skills or goals. Lastly, sponsorship involves advocacy by a senior professional to actively promote someone's career, which Dr. Kane sees as a reciprocal exchange for what trainees do for their mentors. Dr. Joseph Smith was a mentor, coach, and sponsor to Dr. Kane, and he made sure to acknowledge this.

He pivoted to discuss PSA recurrence after radical prostatectomy (RP), a common clinical scenario that still presents many dilemmas: 

  1. PSA Threshold for High-Risk Patients: Should we wait for a specific PSA threshold before intervening in high-risk patients?
  2. PSMA PET/CT Scans: Everyone is getting a PSMA scan even at low PSA levels, and sometimes just months after a pre-op PSMA scan. Is this necessary?
  3. Omitting Short-Term ADT: Can short-term ADT be omitted in patients with a low PSA?
  4. Pelvic Node Dissection: If a patient had a node dissection, should whole pelvic radiation be added to prostate bed radiation?
  5. Positive Pelvic Node: If a patient has a positive pelvic node, should he receive SBRT (metastasis-directed therapy) or whole pelvic radiation therapy?
  6. Treatment for Very High-Risk Patients: How should very high-risk patients be treated?

Dr. Kane highlighted the AUA/ASTRO/SUO clinical practice guideline for decision-making at the time of suspected biochemical recurrence after RP. This guideline represents an excellent summary of current practices in managing biochemical recurrence, compiled through the collaborative effort of three leading societies, making it a tremendous resource for clinicians navigating this complex aspect of prostate cancer management.1

Dr. Kane discussed the RADICALS-RT trial, which randomized 1,396 men between adjuvant and early salvage radiation therapy (PSA > 0.1 on two rising measurements). The study included patients with pT3/4, Gleason scores of 7-10, positive margins, or preoperative PSA ≥10 ng/mL.2

Notably, 93% of the adjuvant group received RT within 6 months, while only 33% of the salvage group received RT within 8 years. The 5-year PSA progression-free survival was 85% for the adjuvant radiotherapy group and 88% for the salvage radiotherapy group (p = 0.56). Interestingly, urinary incontinence was worse at 1 year for the adjuvant radiotherapy group (p = 0.0023), and more individuals in the adjuvant radiotherapy group developed urethral strictures (6%). Freedom from ADT was 93% in the adjuvant group versus 92% in the early salvage group as illustrated in the Kaplan Meier graphics below. To date, Early salvage rather than adjuvant RT is the standard of care for these patients.
Dr. Kane highlighted the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guideline on prostate cancer, which provides a comprehensive classification of risk categories for patients developing biochemical recurrence. This guideline classifies patients into low-risk and high-risk categories based on PSA doubling time and pathological ISUP grade.3
Dr. Kane presented a study from the SEARCH database, led by himself, demonstrating that the first postoperative PSA level is associated with outcomes in patients with node-positive prostate cancer. The study found that patients with a postoperative PSA ≥0.2 ng/mL had a three-fold increased risk of developing metastases. (table below)
The estimated 5-year metastases-free survival rate was 99% for patients with a first postoperative PSA <0.2 ng/mL and 87% if was ≥0.2 ng/mL.
Similarly, Dr. Kane highlighted another study led by the Milan group and Alberto Briganti which confirmed their findings. This study showed that the PSA value at 6 weeks after surgery (PSA <0.1 or ≥0.1 ng/mL) was associated with clinical recurrence. The Kaplan-Meier curves in the study demonstrate an early separation, indicating a significant difference in clinical recurrence rates in patients with a PSA≥0.1 ng/mL.5
Similarly, Dr. Kane highlighted another study led by the Milan group and Alberto Briganti which confirmed their findings. This study showed that the PSA value at 6 weeks after surgery (PSA <0.1 or ≥0.1 ng/mL) was associated with clinical recurrence. The Kaplan-Meier curves in the study demonstrate an early separation, indicating a significant difference in clinical recurrence rates in patients with a PSA≥0.1 ng/mL
Dr. Kane pivoted to discuss the addition of ADT a pelvic lymph node treatment in patients with BCR post-RP undergoing prostate bed salvage RT. He discussed the SPPORT study. This study enrolled 1792 patients with PSA recurrence (PSA between 0.1-2.0) after RP and randomized them to three groups.

  • Prostate bed radiation therapy (PBRT) Arm 1
  • Prostate bed radiation therapy plus short-term ADT (PBRT/ ADT) Arm 2
  • Prostate bed radiation therapy plus short-term ADT and pelvic lymph node radiotherapy (PBRT/ ADT/ PLNRT Arm 3

With a mean follow-up of 8.2 years, the NRG Oncology/RTOG 0534 SPPORT trial demonstrated 5-year freedom from progression rates of 71%, 81%, and 87% for Arms 1, 2, and 3, respectively. The risk of metastasis was reduced by 48% in Arm 3 compared to Arm 1. These findings reinforce that whole pelvic radiotherapy (WPRT) combined with androgen deprivation therapy (ADT) is the best treatment option for patients with biochemical recurrence after radical prostatectomy, offering significant improvements in progression-free survival and reducing the risk of metastasis.6
With a mean follow-up of 8.2 years, the NRG Oncology/RTOG 0534 SPPORT trial demonstrated 5-year freedom from progression rates of 71%, 81%, and 87% for Arms 1, 2, and 3, respectively. The risk of metastasis was reduced by 48% in Arm 3 compared to Arm 1. These findings reinforce that whole pelvic radiotherapy (WPRT) combined with androgen deprivation therapy (ADT) is the best treatment option for patients with biochemical recurrence after radical prostatectomy, offering significant improvements in progression-free survival and reducing the risk of metastasis
In the subgroup analysis of freedom from progression when comparing Arm 3 (WPRT +ADT) vs. Arm 1, all subgroups benefitted from WPRT +ADT.In the subgroup analysis of freedom from progression when comparing Arm 3 (WPRT +ADT) vs. Arm 1, all subgroups benefitted from WPRT +ADT.
Dr. Kane also discussed the progression after local treatment with node-positive disease on imaging, focusing on the OLIGOPELVIS GETUG-P-07 trial. This multicenter phase 2 study evaluated high-dose salvage radiotherapy combined with hormonal therapy in patients with oligo-recurrent pelvic node relapses. The study included 67 patients with five or fewer pelvic nodal metastases detected on Choline PET. After a median follow-up of 49.4 months, the 3-year progression-free survival rate was 58%. Additionally, the 2-year incidence of grade 2 or higher toxicity was 10% for genitourinary (GU) toxicity and 2% for gastrointestinal (GI) toxicity.7image-7.jpg
Dr. Kane also discussed the RTOG 9601 trial, a double-blind, placebo-controlled study that randomized patients with BCR post-RP to receive bicalutamide for 2 years plus RT versus RT alone. Notably, a post hoc analysis of this study stratified patients into Genomic Classifier (GC) risk groups (low, intermediate, and high). This analysis suggested that in the low GC risk group, the addition of ADT may not significantly improve overall survival (OS) but did show benefits in reducing distant metastasis and prostate cancer-specific mortality. Dr Kane mentioned that we have to be cautious of the notion of using PSA as a single predictor to inform ADT, he recommends never to use PSA as a single predictor of ADT considering even in the low PSA group there was some benefit in the original trial.
RTOG 9601 trial, a double-blind, placebo-controlled study that randomized patients with BCR post-RP to receive bicalutamide for 2 years plus RT versus RT alone. Notably, a post hoc analysis of this study stratified patients into Genomic Classifier (GC) risk groups (low, intermediate, and high). This analysis suggested that in the low GC risk group, the addition of ADT may not significantly improve overall survival (OS) but did show benefits in reducing distant metastasis and prostate cancer-specific mortality. Dr Kane mentioned that we have to be cautious of the notion of using PSA as a single predictor to inform ADT, he recommends never to use PSA as a single predictor of ADT considering even in the low PSA group there was some benefit in the original trial.
Dr. Kane noted that ADT+ salvage RT is not a controversy anymore, and all patients should get early salvage RT + 4/6 months of ADT.

Moving on to the oligometastatic setting, metastasis directed therapy has been studied in the ORIOLE and STOMP phase 2 trials, both using different staging modalities, PSMA and conventional imaging, respectively, each trial having no more than 60 patients testing SBRT as MDT which is quite disappointing for this scenario.

Dr. Kane briefly discussed the ORIOLE trial, which recruited patients with 1-3 asymptomatic metastases identified by conventional imaging (MRI, CT, Bone scan). Patients were randomized 2:1 to receive stereotactic body radiotherapy (SBRT) or undergo observation. The composite outcome was progression at 6 months, defined by a PSA rise of 2 ng/dL or 25% above nadir, progression by imaging, or initiation of ADT. The trial enrolled 54 patients, with 36 in the SBRT group and 18 in the observation group.

Progression at 6 months occurred in 19% receiving SBRT and 61% undergoing observation (P = 0.005). Treatment with SBRT reduced the hazard of progression by 70% compared to observation (P =0.002).9
Progression at 6 months occurred in 19% receiving SBRT and 61% undergoing observation (P = 0.005). Treatment with SBRT reduced the hazard of progression by 70% compared to observation (P =0.002).9 

Dr. Kane discussed the growing popularity of salvage lymph node dissection (SLND) with the wide adoption of PSMA PET/CT imaging. He highlighted a retrospective review of 189 patients with rising PSA and nodal-only recurrence after radical prostatectomy who underwent SLND at 11 tertiary referral centers. The clinical recurrence-free survival and biochemical recurrence-free survival at 10 years were 31% and 11%, respectively, indicating that most patients experienced recurrence by 5-6 years. Dr. Kane questioned whether the primary benefit of SLND is merely to delay ADT and whether this delay provides meaningful value to patients. 

A new space of the disease is the non-metastatic castration sensitive space, The EMBARK trial, enrolled High risk PSA recurrence patients PSADT< 9months, a total of 1068 patients randomized to:

  1. Leuprolide alone (n=358)
  2. Leuprolide plus Enzalutamide (n=355)
  3. Enzalutamide monotherapy (n=355)

Dr. Kane presented a study demonstrating that enzalutamide monotherapy and enzalutamide combined with ADT were superior to ADT alone. At 5 years, metastasis-free survival rates were 87.3% in the enzalutamide + ADT arm, 71.4% in the leuprolide-alone group, and 80.0% in the enzalutamide monotherapy group. He suggested that these results support considering enzalutamide monotherapy. However, he noted that 45% of patients developed gynecomastia and breast pain, emphasizing the need to address these side effects before starting therapy. Additionally, patients on enzalutamide monotherapy had slightly higher testosterone levels and retained sexual interest.Dr. Kane presented a study demonstrating that enzalutamide monotherapy and enzalutamide combined with ADT were superior to ADT alone. At 5 years, metastasis-free survival rates were 87.3% in the enzalutamide + ADT arm, 71.4% in the leuprolide-alone group, and 80.0% in the enzalutamide monotherapy group. He suggested that these results support considering enzalutamide monotherapy. However, he noted that 45% of patients developed gynecomastia and breast pain, emphasizing the need to address these side effects before starting therapy. Additionally, patients on enzalutamide monotherapy had slightly higher testosterone levels and retained sexual interest.
Dr. Kane concluded his presentation with the following take home messages:

  • Patients with PSA recurrence after RP can be risk stratified based on grade, stage, PSADT and timing of recurrence
  • Observation with early salvage radiation therapy is the standard of care and should be instituted as early as PSA recurrence is clearly confirmed
  • Short term ADT and whole pelvic radiation therapy improve disease free outcomes and should be used in most patients, particularly high-risk patients
  • Nodal recurrence can be treated with ADT/SBRT or ADT/ regional nodal radiation therapy. Trials are underway to determine the optimal strategy
  • Salvage node dissection for PSMA detected recurrence is associated with limited long-term disease-free outcomes and should be used selectively
  • Optimal candidates have one or two positive nodes by imaging and have a long interval to recurrence
  • High risk patients (PSADT< 9 months) may be best treated with ADT/ Enzalutamide or Enzalutamide 

Presented by: Christopher Kane, MD, Urologist, Dean of Clinical Affairs for UC San Diego School of Medicine and Chief Executive Officer for UC San Diego Health Physician Group

Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) Luis Carlos Sarmiento Angulo Foundation via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2024 Society of Urologic Oncology (SUO) annual meeting held in Dallas, between the 3rd and 6th of December, 2024.

References:

  1. Morgan TM, Boorjian SA, Buyyounouski MK, Chapin BF, Chen DYT, Cheng HH, Chou R, Jacene HA, Kamran SC, Kim SK, Kirkby E, Luckenbaugh AN, Nathanson BJ, Nyame YA, Posadas EM, Tran PT, Chen RC. Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part I: Introduction and Treatment Decision-Making at the Time of Suspected Biochemical Recurrence after Radical Prostatectomy. J Urol. 2024 Apr;211(4):509-517. doi: 10.1097/JU.0000000000003892. Epub 2024 Feb 29. PMID: 38421253.
  2. Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C, Cross W, Logue J, Parulekar W, Payne H, Persad R, Pickering H, Saad F, Anderson J, Bahl A, Bottomley D, Brasso K, Chahal R, Cooke PW, Eddy B, Gibbs S, Goh C, Gujral S, Heath C, Henderson A, Jaganathan R, Jakobsen H, James ND, Kanaga Sundaram S, Lees K, Lester J, Lindberg H, Money-Kyrle J, Morris S, O'Sullivan J, Ostler P, Owen L, Patel P, Pope A, Popert R, Raman R, Røder MA, Sayers I, Simms M, Wilson J, Zarkar A, Parmar MKB, Sydes MR. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet. 2020 Oct 31;396(10260):1413-1421. doi: 10.1016/S0140-6736(20)31553-1. Epub 2020 Sep 28. PMID: 33002429.
  3. Tilki D, van den Bergh RCN, Briers E, Van den Broeck T, Brunckhorst O, Darraugh J, Eberli D, De Meerleer G, De Santis M, Farolfi A, Gandaglia G, Gillessen S, Grivas N, Henry AM, Lardas M, J L H van Leenders G, Liew M, Linares Espinos E, Oldenburg J, van Oort IM, Oprea-Lager DE, Ploussard G, Roberts MJ, Rouvière O, Schoots IG, Schouten N, Smith EJ, Stranne J, Wiegel T, Willemse PM, Cornford P. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer. Part II-2024 Update: Treatment of Relapsing and Metastatic Prostate Cancer. Eur Urol. 2024 Aug;86(2):164-182. doi: 10.1016/j.eururo.2024.04.010. Epub 2024 Apr 29. PMID: 38688773.
  4. McDonald ML, Howard LE, Aronson WJ, Terris MK, Cooperberg MR, Amling CL, Freedland SJ, Kane CJ. First postoperative PSA is associated with outcomes in patients with node positive prostate cancer: Results from the SEARCH database. Urol Oncol. 2018 May;36(5):239.e17-239.e25. doi: 10.1016/j.urolonc.2018.01.005. Epub 2018 Feb 9. PMID: 29429895.
  5. Bianchi L, Nini A, Bianchi M, Gandaglia G, Fossati N, Suardi N, Moschini M, Dell'Oglio P, Schiavina R, Montorsi F, Briganti A. The Role of Prostate-specific Antigen Persistence After Radical Prostatectomy for the Prediction of Clinical Progression and Cancer-specific Mortality in Node-positive Prostate Cancer Patients. Eur Urol. 2016 Jun;69(6):1142-8. doi: 10.1016/j.eururo.2015.12.010. Epub 2015 Dec 31. PMID: 26749093.
  6. Pollack A, Karrison TG, Balogh AG, Gomella LG, Low DA, Bruner DW, Wefel JS, Martin AG, Michalski JM, Angyalfi SJ, Lukka H, Faria SL, Rodrigues GB, Beauchemin MC, Lee RJ, Seaward SA, Allen AM, Monitto DC, Seiferheld W, Sartor O, Feng F, Sandler HM. The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. Lancet. 2022 May 14;399(10338):1886-1901. doi: 10.1016/S0140-6736(21)01790-6. PMID: 35569466; PMCID: PMC9819649.
  7. Supiot S, Vaugier L, Pasquier D, Buthaud X, Magné N, Peiffert D, Sargos P, Crehange G, Pommier P, Loos G, Hasbini A, Latorzeff I, Silva M, Denis F, Lagrange JL, Morvan C, Campion L, Blanc-Lapierre A. OLIGOPELVIS GETUG P07, a Multicenter Phase II Trial of Combined High-dose Salvage Radiotherapy and Hormone Therapy in Oligorecurrent Pelvic Node Relapses in Prostate Cancer. Eur Urol. 2021 Oct;80(4):405-414. doi: 10.1016/j.eururo.2021.06.010. Epub 2021 Jul 8. PMID: 34247896.
  8. Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, Sartor O, Patel MP, Bahary JP, Zietman AL, Pisansky TM, Zeitzer KL, Lawton CA, Feng FY, Lovett RD, Balogh AG, Souhami L, Rosenthal SA, Kerlin KJ, Dignam JJ, Pugh SL, Sandler HM; NRG Oncology RTOG. Radiation with or without Antiandrogen Therapy in Recurrent Prostate Cancer. N Engl J Med. 2017 Feb 2;376(5):417-428. doi: 10.1056/NEJMoa1607529. PMID: 28146658; PMCID: PMC5444881.
  9. Phillips R, Shi WY, Deek M, Radwan N, Lim SJ, Antonarakis ES, Rowe SP, Ross AE, Gorin MA, Deville C, Greco SC, Wang H, Denmeade SR, Paller CJ, Dipasquale S, DeWeese TL, Song DY, Wang H, Carducci MA, Pienta KJ, Pomper MG, Dicker AP, Eisenberger MA, Alizadeh AA, Diehn M, Tran PT. Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer: The ORIOLE Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):650-659. doi: 10.1001/jamaoncol.2020.0147. PMID: 32215577; PMCID: PMC7225913.
  10. Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Tarazi J, Sridharan S, Sugg J, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Zohren F, Shore ND. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023 Oct 19;389(16):1453-1465. doi: 10.1056/NEJMoa2303974. PMID: 37851874.